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Sample records for r-flurbiprofen reduces neuropathic

  1. R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids

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    Marian, Claudiu; Häussler, Annett; Wijnvoord, Nina; Ziebell, Simone; Metzner, Julia; Koch, Marco; Myrczek, Thekla; Bechmann, Ingo; Kuner, Rohini; Costigan, Michael; Dehghani, Faramarz; Geisslinger, Gerd; Tegeder, Irmgard

    2010-01-01

    Background R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. Methodology/Principal Findings We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH) and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARγ and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. Conclusion Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain. PMID:20498712

  2. R-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids.

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    Philipp Bishay

    Full Text Available BACKGROUND: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB, which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARgamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. CONCLUSION: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain.

  3. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice.

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    Schmitz, Katja; de Bruin, Natasja; Bishay, Philipp; Männich, Julia; Häussler, Annett; Altmann, Christine; Ferreirós, Nerea; Lötsch, Jörn; Ultsch, Alfred; Parnham, Michael J; Geisslinger, Gerd; Tegeder, Irmgard

    2014-11-01

    R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4(+)CD25(+)FoxP3(+) regulatory T cells, CTLA4(+) inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R-flurbiprofen in human MS, and its low toxicity may justify a clinical trial. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  4. R-Flurbiprofen Traps Prostaglandins within Cells by Inhibition of Multidrug Resistance-Associated Protein-4.

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    Wobst, Ivonne; Ebert, Lisa; Birod, Kerstin; Wegner, Marthe-Susanna; Hoffmann, Marika; Thomas, Dominique; Angioni, Carlo; Parnham, Michael J; Steinhilber, Dieter; Tegeder, Irmgard; Geisslinger, Gerd; Grösch, Sabine

    2016-12-30

    R -flurbiprofen is the non-COX-inhibiting enantiomer of flurbiprofen and is not converted to S -flurbiprofen in human cells. Nevertheless, it reduces extracellular prostaglandin E₂ (PGE₂) in cancer or immune cell cultures and human extracellular fluid. Here, we show that R -flurbiprofen acts through a dual mechanism: (i) it inhibits the translocation of cPLA 2α to the plasma membrane and thereby curtails the availability of arachidonic acid and (ii) R -flurbiprofen traps PGE₂ inside of the cells by inhibiting multidrug resistance-associated protein 4 (MRP4, ABCC4), which acts as an outward transporter for prostaglandins. Consequently, the effects of R -flurbiprofen were mimicked by RNAi-mediated knockdown of MRP4. Our data show a novel mechanism by which R -flurbiprofen reduces extracellular PGs at physiological concentrations, particularly in cancers with high levels of MRP4, but the mechanism may also contribute to its anti-inflammatory and immune-modulating properties and suggests that it reduces PGs in a site- and context-dependent manner.

  5. R-Flurbiprofen Traps Prostaglandins within Cells by Inhibition of Multidrug Resistance-Associated Protein-4

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    Ivonne Wobst

    2016-12-01

    Full Text Available R-flurbiprofen is the non-COX-inhibiting enantiomer of flurbiprofen and is not converted to S-flurbiprofen in human cells. Nevertheless, it reduces extracellular prostaglandin E2 (PGE2 in cancer or immune cell cultures and human extracellular fluid. Here, we show that R-flurbiprofen acts through a dual mechanism: (i it inhibits the translocation of cPLA2α to the plasma membrane and thereby curtails the availability of arachidonic acid and (ii R-flurbiprofen traps PGE2 inside of the cells by inhibiting multidrug resistance–associated protein 4 (MRP4, ABCC4, which acts as an outward transporter for prostaglandins. Consequently, the effects of R-flurbiprofen were mimicked by RNAi-mediated knockdown of MRP4. Our data show a novel mechanism by which R-flurbiprofen reduces extracellular PGs at physiological concentrations, particularly in cancers with high levels of MRP4, but the mechanism may also contribute to its anti-inflammatory and immune-modulating properties and suggests that it reduces PGs in a site- and context-dependent manner.

  6. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

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    Kukar, Thomas; Prescott, Sonya; Eriksen, Jason L; Holloway, Vallie; Murphy, M Paul; Koo, Edward H; Golde, Todd E; Nicolle, Michelle M

    2007-01-01

    Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its

  7. Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice

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    Koo Edward H

    2007-07-01

    Full Text Available Abstract Background Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs is associated with a reduced incidence of Alzheimer's disease (AD. We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice. Results A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning. Conclusion We have found that chronic administration of R-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition

  8. R-flurbiprofen improves tau, but not Aß pathology in a triple transgenic model of Alzheimer's disease.

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    Carreras, Isabel; McKee, Ann C; Choi, Ji-Kyung; Aytan, Nurgul; Kowall, Neil W; Jenkins, Bruce G; Dedeoglu, Alpaslan

    2013-12-06

    We have previously reported that chronic ibuprofen treatment improves cognition and decreases intracellular Aß and phosphorylated-tau levels in 3xTg-AD mice. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that independently of its anti-inflammatory effects has anti-amyloidogenic activity as a gamma-secretase modulator (GSM) and both activities have the potential to decrease Aß pathology. To further understand the effects of NSAIDs in 3xTg-AD mice, we treated 3xTg-AD mice with R-flurbiprofen, an enantiomer of the NSAID flurbiprofen that maintains the GSM activity but has greatly reduced anti-inflammatory activity, and analyzed its effect on cognition, Aß, tau, and the neurochemical profile of the hippocampus. Treatment with R-flurbiprofen from 5 to 7 months of age resulted in improved cognition on the radial arm water maze (RAWM) test and decreased the level of hyperphosphorylated tau immunostained with AT8 and PHF-1 antibodies. No significant changes in the level of Aß (using 6E10 and NU-1 antibodies) were detected. Using magnetic resonance spectroscopy (MRS) we found that R-flurbiprofen treatment decreased the elevated level of glutamine in 3xTg-AD mice down to the level detected in non-transgenic mice. Glutamine levels correlated with PHF-1 immunostained hyperphosphorylated tau. We also found an inverse correlation between the concentration of glutamate and learning across all the mice in the study. Glutamine and glutamate, neurochemicals that shuttles between neurons and astrocytes to maintain glutamate homeostasis in the synapses, deserve further attention as MR markers of cognitive function. © 2013 Published by Elsevier B.V.

  9. Orofacial neuropathic pain reduces spontaneous burrowing behavior in rats.

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    Deseure, K; Hans, G

    2018-07-01

    It was recently reported that spontaneous burrowing behavior is decreased after tibial nerve transection, spinal nerve transection and partial sciatic nerve ligation. It was proposed that spontaneous burrowing could be used as a measure of the impact of neuropathic pain after peripheral nerve injury. It has remained unclear whether the reduction in burrowing behavior is caused directly by pain or hypersensitivity in the affected limbs, making it more difficult to perform burrowing, or by a pain induced decrease in the general wellbeing, thus reducing the motivation to burrow. We studied burrowing behavior after infraorbital nerve injury, a model of orofacial neuropathic pain that does not affect the limbs. Burrowing behavior was significantly reduced after infraorbital nerve injury. Isolated face grooming and responsiveness to mechanical von Frey stimulation of the infraorbital nerve territory were significantly increased after infraorbital nerve injury, indicative, respectively, of spontaneous pain and mechanical allodynia. It is concluded that spontaneous burrowing may provide a measure of the global impact of pain on the animal's wellbeing after peripheral nerve injury and incorporation of this behavioral assay in preclinical drug testing may improve the predictive validity of currently used pain models. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

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    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Effect of Patient Education on Reducing Medication in Spinal Cord Injury Patients With Neuropathic Pain.

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    Shin, Ji Cheol; Kim, Na Young; Chang, Shin Hye; Lee, Jae Joong; Park, Han Kyul

    2017-08-01

    To determine whether providing education about the disease pathophysiology and drug mechanisms and side effects, would be effective for reducing the use of pain medication while appropriately managing neurogenic pain in spinal cord injury (SCI) patients. In this prospective study, 109 patients with an SCI and neuropathic pain, participated in an educational pain management program. This comprehensive program was specifically created, for patients with an SCI and neuropathic pain. It consisted of 6 sessions, including educational training, over a 6-week period. Of 109 patients, 79 (72.5%) initially took more than two types of pain medication, and this decreased to 36 (33.0%) after the educational pain management program was completed. The mean pain scale score and the number of pain medications decreased, compared to the baseline values. Compared to the non-response group, the response group had a shorter duration of pain onset (p=0.004), and a higher initial number of different medications (ppain management program, can be a valuable complement to the treatment of spinal cord injured patients with neuropathic pain. Early intervention is important, to prevent patients from developing chronic SCI-related pain.

  12. Combined inhibition of monoacylglycerol lipase and cyclooxygenases synergistically reduces neuropathic pain in mice

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    Crowe, Molly S; Leishman, Emma; Banks, Matthew L; Gujjar, Ramesh; Mahadevan, Anu; Bradshaw, Heather B; Kinsey, Steven G

    2015-01-01

    Background and Purpose Neuropathic pain is commonly treated with GABA analogues, steroids or non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit one or more COX isozymes but chronic COX inhibition paradoxically increases gastrointestinal inflammation and risk of unwanted cardiovascular events. The cannabinoids also have analgesic and anti-inflammatory properties and reduce neuropathic pain in animal models. The present study investigated the analgesic effects of inhibiting both monoacylglycerol lipase (MAGL) and COX enzymes, using low doses of both inhibitors. Experimental Approach Mice subjected to chronic constriction injury (CCI) were tested for mechanical and cold allodynia after administration of the MAGL inhibitor, JZL184, or the non-selective COX inhibitor diclofenac. Then, both drugs were co-administered at fixed dose proportions of 1:3, 1:1 and 3:1, based on their ED50 values. PGs, endocannabinoids and related lipids were quantified in lumbar spinal cord. Key Results Combining low doses of JZL184 and diclofenac synergistically attenuated mechanical allodynia and additively reduced cold allodynia. The cannabinoid CB1 receptor antagonist, rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the analgesic effects of the JZL184 and diclofenac combination on mechanical allodynia, implying that CB1 receptors were primarily responsible for the anti-allodynia. Diclofenac alone and with JZL184 significantly reduced PGE2 and PGF2α in lumbar spinal cord tissue, whereas JZL184 alone caused significant increases in the endocannabinoid metabolite, N-arachidonoyl glycine. Conclusions and Implications Combining COX and MAGL inhibition is a promising therapeutic approach for reducing neuropathic pain with minimal side effects. PMID:25393148

  13. An examination of the thermodynamics of fusion, vaporization, and sublimation of (R,S)- and (R)-flurbiprofen by correlation gas chromatography.

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    Umnahanant, Patamaporn; Hasty, Darrell; Chickos, James

    2012-06-01

    The vaporization, fusion, and sublimation enthalpies of (R,S)- and (R)-flurbiprofen at T = 298.15 K are reported and compared with literature values when available. Correlation gas chromatography experiments were first performed to identify appropriate standards that could be used for materials containing a single fluorine substituent. Subsequent correlations resulted in a vaporization enthalpy for (R,S)-flurbiprofen and (R)-flurbiprofen, ΔH(vap) (298.15 K), of (127.5 ± 5.5) and (127.4 ± 4.7) kJ mol, respectively. Fusion enthalpies, ΔH(fus) (387 K), of (28.2 ± and, ΔH(fus) (381 K), (22.8 ± kJ mol(-1) were also measured by differential scanning calorimetry for the racemic and chiral forms of flurbiprofen. Adjusted to T = 298.15 K and combined with the vaporization enthalpy resulted in sublimation enthalpies, ΔH(sub) (298.15 K), of (155.6 ± 5.8) and (145.1 ± 5.7) kJ mol(-1) for (R,S)- and (R)-flurbiprofen, respectively. The fusion enthalpy measured for the racemic form was in excellent agreement with the literature value, while the sublimation enthalpy varies substantially from previous work. Two weak solid-solid phase transitions were also observed for (R)-flurbiprofen at T = 353.9 K (0.30 ± 0.1) and 363.2 K (0.21 ± 0.03) kJ · mol(-1). Copyright © 2012 Wiley Periodicals, Inc.

  14. Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection.

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    Martini, Alessandra Cadete; Berta, Temugin; Forner, Stefânia; Chen, Gang; Bento, Allisson Freire; Ji, Ru-Rong; Rae, Giles Alexander

    2016-04-08

    Spinal cord injury (SCI) is a severe neurological disorder with many disabling consequences, including persistent neuropathic pain, which develops in about 40 % of SCI patients and is induced and sustained by excessive and uncontrolled spinal neuroinflammation. Here, we have evaluated the effects of lipoxin A4 (LXA4), a member of a unique class of endogenous lipid mediators with both anti-inflammatory and analgesic properties, on spinal neuroinflammation and chronic pain in an experimental model of SCI. Spinal hemisection at T10 was carried out in adult male CD1 mice and Wistar rats. To test if LXA4 can reduce neuroinflammation and neuropathic pain, each animal received two intrathecal injections of LXA4 (300 pmol) or vehicle at 4 and 24 h after SCI. Sensitivity to mechanical stimulation of the hind paws was evaluated using von Frey monofilaments, and neuroinflammation was tested by measuring the mRNA and/or protein expression levels of glial markers and cytokines in the spinal cord samples after SCI. Also, microglia cultures prepared from murine cortical tissue were used to assess the direct effects of LXA4 on microglial activation and release of pro-inflammatory TNF-α. LXA4 treatment caused significant reductions in the intensity of mechanical pain hypersensitivity and spinal expression levels of microglial markers and pro-inflammatory cytokines induced by SCI, when compared to rodents receiving control vehicle injections. Notably, the increased expressions of the microglial marker IBA-1 and of the pro-inflammatory cytokine TNF-α were the most affected by the LXA4 treatment. Furthermore, cortical microglial cultures expressed ALX/FPR2 receptors for LXA4 and displayed potentially anti-inflammatory responses upon challenge with LXA4. Collectively, our results suggest that LXA4 can effectively modulate microglial activation and TNF-α release through ALX/FPR2 receptors, ultimately reducing neuropathic pain in rodents after spinal cord hemisection. The dual anti

  15. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

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    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor. Copyright © 2016. Published by Elsevier Ireland Ltd.

  16. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain.

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    Ragavendran, J Vaigunda; Laferrière, André; Xiao, Wen Hua; Bennett, Gary J; Padi, Satyanarayana S V; Zhang, Ji; Coderre, Terence J

    2013-01-01

    Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle, or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α(2)-adrenergic (α(2)A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent antiallodynic effects in rats with chronic postischemia pain, and the antiallodynic dose-response curves of PDE and PA inhibitors were shifted 2.5- to 10-fold leftward when combined with nonanalgesic doses of α(2)A receptor agonists or NO donors. Topical combinations also produced significant antiallodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 hours after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α(2)A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain. This article presents the synergistic antiallodynic effects of combinations of α(2)A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest that effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected

  17. Virtual reality-augmented neurorehabilitation improves motor function and reduces neuropathic pain in patients with incomplete spinal cord injury.

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    Villiger, Michael; Bohli, Dominik; Kiper, Daniel; Pyk, Pawel; Spillmann, Jeremy; Meilick, Bruno; Curt, Armin; Hepp-Reymond, Marie-Claude; Hotz-Boendermaker, Sabina; Eng, Kynan

    2013-10-01

    Neurorehabilitation interventions to improve lower limb function and neuropathic pain have had limited success in people with chronic, incomplete spinal cord injury (iSCI). We hypothesized that intense virtual reality (VR)-augmented training of observed and executed leg movements would improve limb function and neuropathic pain. Patients used a VR system with a first-person view of virtual lower limbs, controlled via movement sensors fitted to the patient's own shoes. Four tasks were used to deliver intensive training of individual muscles (tibialis anterior, quadriceps, leg ad-/abductors). The tasks engaged motivation through feedback of task success. Fourteen chronic iSCI patients were treated over 4 weeks in 16 to 20 sessions of 45 minutes. Outcome measures were 10 Meter Walking Test, Berg Balance Scale, Lower Extremity Motor Score, Spinal Cord Independence Measure, Locomotion and Neuropathic Pain Scale (NPS), obtained at the start and at 4 to 6 weeks before intervention. In addition to positive changes reported by the patients (Patients' Global Impression of Change), measures of walking capacity, balance, and strength revealed improvements in lower limb function. Intensity and unpleasantness of neuropathic pain in half of the affected participants were reduced on the NPS test. Overall findings remained stable 12 to 16 weeks after termination of the training. In a pretest/posttest, uncontrolled design, VR-augmented training was associated with improvements in motor function and neuropathic pain in persons with chronic iSCI, several of which reached the level of a minimal clinically important change. A controlled trial is needed to compare this intervention to active training alone or in combination.

  18. Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides.

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    Pannell, Maria; Labuz, Dominika; Celik, Melih Ö; Keye, Jacqueline; Batra, Arvind; Siegmund, Britta; Machelska, Halina

    2016-10-07

    During the inflammation which occurs following nerve damage, macrophages are recruited to the site of injury. Phenotypic diversity is a hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti-inflammatory M2 populations. Our aim in this study was to investigate the ability of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine their relative contribution to the modulation of neuropathic pain. Mouse bone marrow-derived cells were cultured as unstimulated M0 macrophages or were stimulated into an M1 phenotype using lipopolysaccharide and interferon-γ or into an M2 phenotype using interleukin-4. The macrophage phenotypes were verified using flow cytometry for surface marker analysis and cytokine bead array for cytokine profile assessment. Opioid peptide levels were measured by radioimmunoassay and enzyme immunoassay. As a model of neuropathic pain, a chronic constriction injury (CCI) of the sciatic nerve was employed. Polarized M0, M1, and M2 macrophages (5 × 10 5 cells) were injected perineurally twice, on days 14 and 15 following CCI or sham surgery. Mechanical and heat sensitivity were measured using the von Frey and Hargreaves tests, respectively. To track the injected macrophages, we also transferred fluorescently stained polarized cells and analyzed the surface marker profile of endogenous and injected cells in the nerves ex vivo. Compared to M0 and M1 cells, M2 macrophages contained and released higher amounts of opioid peptides, including Met-enkephalin, dynorphin A (1-17), and β-endorphin. M2 cells transferred perineurally at the nerve injury site reduced mechanical, but not heat hypersensitivity following the second injection. The analgesic effect was reversed by the perineurally applied opioid receptor antagonist naloxone methiodide. M2 cells did not affect sensitivity following sham surgery. Neither M0 nor M1 cells altered mechanical and heat sensitivity in CCI or sham-operated animals. Tracing the

  19. Reduced basal ganglia μ-opioid receptor availability in trigeminal neuropathic pain: A pilot study

    Directory of Open Access Journals (Sweden)

    DosSantos Marcos

    2012-09-01

    Full Text Available Abstract Background Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. Findings In this study, we examined the regional μ-opioid receptor (μOR availability in vivo (non-displaceable binding potential BPND of TNP patients with positron emission tomography (PET using the μOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced μOR BPND in the left nucleus accumbens (NAc, an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the μOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. Conclusions Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous μ-opioid system, rather than only to the peripheral pathology. The decreased availability of μORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.

  20. The Edible Brown Seaweed Ecklonia cava Reduces Hypersensitivity in Postoperative and Neuropathic Pain Models in Rats

    Directory of Open Access Journals (Sweden)

    Jae Goo Kim

    2014-06-01

    Full Text Available The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05. Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats.

  1. Aging Enables Ca2+ Overload and Apoptosis Induced by Amyloid-β Oligomers in Rat Hippocampal Neurons: Neuroprotection by Non-Steroidal Anti-Inflammatory Drugs and R-Flurbiprofen in Aging Neurons.

    Science.gov (United States)

    Calvo-Rodríguez, María; García-Durillo, Mónica; Villalobos, Carlos; Núñez, Lucía

    2016-07-22

    The most important risk factor for Alzheimer's disease (AD) is aging. Neurotoxicity in AD has been linked to dyshomeostasis of intracellular Ca2+ induced by small aggregates of the amyloid-β peptide 1-42 (Aβ42 oligomers). However, how aging influences susceptibility to neurotoxicity induced by Aβ42 oligomers is unknown. In this study, we used long-term cultures of rat hippocampal neurons, a model of neuronal in vitro aging, to investigate the contribution of aging to Ca2+ dishomeostasis and neuron cell death induced by Aβ42 oligomers. In addition, we tested whether non-steroidal anti-inflammatory drugs (NSAIDs) and R-flurbiprofen prevent apoptosis acting on subcellular Ca2+ in aged neurons. We found that Aβ42 oligomers have no effect on young hippocampal neurons cultured for 2 days in vitro (2 DIV). However, they promoted apoptosis modestly in mature neurons (8 DIV) and these effects increased dramatically after 13 DIV, when neurons display many hallmarks of in vivo aging. Consistently, cytosolic and mitochondrial Ca2+ responses induced by Aβ42 oligomers increased dramatically with culture age. At low concentrations, NSAIDs and the enantiomer R-flurbiprofen lacking anti-inflammatory activity prevent Ca2+ overload and neuron cell death induced by Aβ42 oligomers in aged neurons. However, at high concentrations R-flurbiprofen induces apoptosis. Thus, Aβ42 oligomers promote Ca2+ overload and neuron cell death only in aged rat hippocampal neurons. These effects are prevented by low concentrations of NSAIDs and R-flurbiprofen acting on mitochondrial Ca2+ overload.

  2. APP/SOD1 overexpressing mice present reduced neuropathic pain sensitivity.

    Science.gov (United States)

    Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Olakowska, Edyta; Lewin-Kowalik, Joanna; London, Jacqueline

    2011-07-15

    There are controversies regarding pain expression in mentally disabled people, including Down syndrome patients. The aim of this study was to examine neuropathic pain-related behavior and peripheral nerve regeneration in mouse model of Down syndrome. Sciatic nerves of double transgenic mice, overexpressing both amyloid precursor protein (APP) and Cu/Zn superoxide dismutase (SOD1) genes, and FVB/N wild type mice were transected and immediately resutured. Evaluation of autotomy and functional recovery was carried out during 4-week follow-up. We found markedly less severe autotomy in transgenic animals, although the onset of autotomy was significantly delayed in control mice. Interestingly, neuroma formation at the injury site was significantly more prominent in transgenic animals. Sciatic function index outcome was better in transgenic mice than in wild-type group. Histological evaluation revealed no statistically significant differences in the number of GAP-43-positive growth cones and macrophages in the distal stump of the transected nerve between groups. However, in transgenic animals, the regenerating axons were arranged more chaotically. The number of Schwann cells in the distal stump of the transected nerves was significantly lower in transgenic mice. The number of surviving motoneurons was markedly decreased in transgenic group. We measured also the atrophy of denervated muscles and found it decreased in APP/SOD1 overexpressing mice. Taken together, in this model of Down syndrome, we observed increased neuroma formation and decreased autotomy after peripheral nerve injury. Our findings suggest that APP/SOD1 overexpressing mice are less sensitive for neuropathic pain associated with neuroma. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Managing neuropathic pain in dogs

    Directory of Open Access Journals (Sweden)

    Sarah A Moore

    2016-02-01

    Full Text Available Disorders of the somatosensory system such as neuropathic pain are common in people with chronic neurologic and musculoskeletal diseases, yet these conditions remain an underappreciated morbidity in our veterinary patients. This is likely because assessment of neuropathic pain in people relies heavily on self-reporting, something our veterinary patients are not able to do. The development of neuropathic pain is a complex phenomenon, and concepts related to it are frequently not addressed in the standard veterinary medical curriculum such that veterinarians may not recognize this as a potential problem in patients. The goals of this review are to discuss basic concepts in the pathophysiology of neuropathic pain, provide definitions for common clinical terms used in association with the condition, and discuss available medical treatment options for dogs with neuropathic pain. The development of neuropathic pain involves key mechanisms such as ectopic afferent nerve activity, peripheral sensitization, central sensitization, impaired inhibitory modulation, and activation of microglia. Treatments aimed at reducing neuropathic pain are targeted at one or more of these mechanisms. Several drugs are commonly used in the veterinary clinical setting to treat neuropathic pain. These include gabapentin, pregabalin, amantadine, and amitriptyline. Proposed mechanisms of action for each drug, and known pharmacokinetic profiles in dogs are discussed. Strong evidence exists in the human literature for the utility of most of these treatments, but clinical veterinary-specific literature is currently limited. Future studies should focus on objective methods to document neuropathic pain and monitor response to therapy in our veterinary patients.

  4. Activation of Spinal α2-Adrenoceptors Using Diluted Bee Venom Stimulation Reduces Cold Allodynia in Neuropathic Pain Rats

    Directory of Open Access Journals (Sweden)

    Suk-Yun Kang

    2012-01-01

    Full Text Available Cold allodynia is an important distinctive feature of neuropathic pain. The present study examined whether single or repetitive treatment of diluted bee venom (DBV reduced cold allodynia in sciatic nerve chronic constriction injury (CCI rats and whether these effects were mediated by spinal adrenergic receptors. Single injection of DBV (0.25 or 2.5 mg/kg was performed into Zusanli acupoint 2 weeks post CCI, and repetitive DBV (0.25 mg/kg was injected for 2 weeks beginning on day 15 after CCI surgery. Single treatment of DBV at a low dose (0.25 mg/kg did not produce any anticold allodynic effect, while a high dose of DBV (2.5 mg/kg significantly reduced cold allodynia. Moreover, this effect of high-dose DBV was completely blocked by intrathecal pretreatment of idazoxan (α2-adrenoceptor antagonist, but not prazosin (α1-adrenoceptor antagonist or propranolol (nonselective β-adrenoceptor antagonist. In addition, coadministration of low-dose DBV (0.25 mg/kg and intrathecal clonidine (α2-adrenoceptor agonist synergically reduced cold allodynia. On the other hand, repetitive treatments of low-dose DBV showing no motor deficit remarkably suppressed cold allodynia from 7 days after DBV treatment. This effect was also reversed by intrathecal idazoxan injection. These findings demonstrated that single or repetitive stimulation of DBV could alleviate CCI-induced cold allodynia via activation of spinal α2-adrenoceptor.

  5. Neuropathic pain

    Directory of Open Access Journals (Sweden)

    Giuseppe Re

    2009-02-01

    Full Text Available Neuropathic pain is the expression of a dysfunction or primary lesion of a nerve in the peripheral or central nervous system, or both, rather than the biological signal transmitted by the nerve following peripheral nociceptor activation. It represents about 20% of all painful syndromes, with an estimated prevalence of 1.5%, however is actual incidence is hard to pinpoint due to the difficulties encountered in distinguishing it from chronic pain, of which it represents a significant percentage, on account of the not infrequent concurrence of conditions. It is crucial to recognise the variety of symptoms with which it can present: these can be negative and positive and, in turn, motor, sensitive and autonomic. In public health terms, it is important to emphasise that the diagnosis of neuropathic pain does not in most cases require sophisticated procedures and does not therefore weigh on health expenditure. In clinical practice, a validated scale (the LANSS is mentioned is useful for identifying patients presenting neuropathic pain symptoms. Therapy is based on three categories of medication: tricyclic antidepressants, anti-epileptics and opioids at high doses: neuropathic pain has a bad reputation for often resisting common therapeutic approaches and responding less well that nociceptor pain to monotherapy. Therapeutic strategies are all the more adequate the more they are based on symptoms and therefore on the pain generation mechanisms, although the recommendations are dictated more by expert opinions that double-blind randomised trials.

  6. IL-10 mediated by herpes simplex virus vector reduces neuropathic pain induced by HIV gp120 combined with ddC in rats.

    Science.gov (United States)

    Zheng, Wenwen; Huang, Wan; Liu, Shue; Levitt, Roy C; Candiotti, Keith A; Lubarsky, David A; Hao, Shuanglin

    2014-07-30

    HIV-associated sensory neuropathy affects over 50% of HIV patients and is a common peripheral nerve complication of HIV infection and highly active antiretroviral therapy (HAART). Evidence shows that painful HIV sensory neuropathy is influenced by neuroinflammatory events that include the proinflammatory molecules, MAP Kinase, tumor necrosis factor-α (TNFα), stromal cell-derived factor 1-α (SDF1α), and C-X-C chemokine receptor type 4 (CXCR4). However, the exact mechanisms of painful HIV sensory neuropathy are not known, which hinders our ability to develop effective treatments. In this study, we investigated whether inhibition of proinflammatory factors reduces the HIV-associated neuropathic pain state. Neuropathic pain was induced by peripheral HIV coat protein gp120 combined with 2',3'-dideoxycytidine (ddC, one of the nucleoside reverse transcriptase inhibitors (NRTIs)). Mechanical threshold was tested using von Frey filament fibers. Non-replicating herpes simplex virus (HSV) vectors expressing interleukin 10 (IL10) were inoculated into the hindpaws of rats. The expression of TNFα, SDF1α, and CXCR4 in the lumbar spinal cord and L4/5 dorsal root ganglia (DRG) was examined using western blots. IL-10 expression mediated by the HSV vectors resulted in a significant elevation of mechanical threshold. The anti-allodynic effect of IL-10 expression mediated by the HSV vectors lasted more than 3 weeks. The area under the effect-time curves (AUC) in mechanical threshold in rats inoculated with the HSV vectors expressing IL-10, was increased compared with the control vectors, indicating antinociceptive effect of the IL-10 vectors. The HSV vectors expressing IL-10 also concomitantly reversed the upregulation of p-p38, TNFα, SDF1α, and CXCR4 induced by gp120 in the lumbar spinal dorsal horn and/or the DRG at 2 and/or 4 weeks. The blocking of the signaling of these proinflammatory molecules is able to reduce HIV-related neuropathic pain, which provide a novel

  7. Minocycline through attenuation of oxidative stress and inflammatory response reduces the neuropathic pain in a rat model of chronic constriction injury

    Directory of Open Access Journals (Sweden)

    Abolfazl Abbaszadeh

    2018-02-01

    Full Text Available Objective(s: Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI. Materials and Methods: In this study four groups (n = 6–8 of rats were used as follows: Sham, CCI, CCI + minocycline (MIN 10 mg/Kg (IP and CCI + MIN 30 mg/Kg (IP. On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1β, Glutathione peroxidase (GPx, Superoxide dismutase (SOD and Malondialdehyde (MDA. Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated. Results: Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1β. Antioxidative enzymes (SOD, MDA, and GPx were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline. Conclusion: It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress.

  8. Neuropathic pain in primary care

    African Journals Online (AJOL)

    The operative difference is that neuropathic pain represents a delayed, ongoing response to damage that is no longer acute ... Postsurgical pain (including post- mastectomy and phantom limb pain). Spinal cord injury pain ... Management of neuropathic pain. Neuropathic pain tends to exhibit a relatively poor response.

  9. Melanocortins and Neuropathic Pain

    NARCIS (Netherlands)

    Vrinten, Dorien Henriëtte

    2003-01-01

    Neuropathic pain (pain initiated by a lesion or dysfunction of the nervous system) is characterised by symptoms such as allodynia (pain due to a stimulus that does not normally provoke pain) and hyperalgesia (an increased response to a stimulus that is normally painful). It constitutes a major

  10. The potential role of neuropathic mechanisms in dry eye syndromes.

    Science.gov (United States)

    Mcmonnies, Charles W

    Dry eye syndromes can involve both nociceptive and neuropathic symptoms. Nociceptive symptoms are the normal physiological responses to noxious stimuli. Neuropathic symptoms are caused by a lesion or disease of the somatosensory nervous system and can be the result of hypersensitisation of peripheral or central corneal and conjunctival somatosensory nerves. For example, inflammation could induce neuroplastic peripheral sensitisation of the ocular surface or lid wiper and exacerbate nociceptive symptoms. Neuropathic symptoms may explain the incommensurate relation between signs and symptoms in some dry eye syndromes although absence of signs of a dry eye syndrome may also be a consequence of inappropriate methods used when examining for them. Involvement of neuropathic mechanisms may also help explain dry eye symptoms which occur in association with reduced corneal sensitivity. This review includes a discussion of the potential for ocular symptoms involving neuropathic mechanisms to contribute to psychosocial problems such as depression, stress, anxiety and sleep disorders as well as for these types of psychosocial problems to contribute to neuropathic mechanisms and dry eye syndromes. Failure to consider the possibility that neuropathic mechanisms can contribute to dry eye syndromes may reduce accuracy of diagnosis and the suitability of treatment provided. Dry eye symptoms in the absence of commensurate evidence of tear dysfunction, and unsatisfactory response to tear dysfunction therapies should prompt consideration of neuropathic mechanisms being involved. Symptoms which persist after local anaesthetic instillation are more likely to be neuropathic in origin. Reducing inflammation may help limit any associated neuroplastic hypersensitivity. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  11. Duloxetine and 8-OH-DPAT, but not fluoxetine, reduce depression-like behaviour in an animal model of chronic neuropathic pain.

    Science.gov (United States)

    Hu, Bing; Doods, Henri; Treede, Rolf-Detlef; Ceci, Angelo

    2016-04-21

    The current study assessed whether antidepressant and/or antinociceptive drugs, duloxetine, fluoxetine as well as (±)-8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), are able to reverse depression-like behaviour in animals with chronic neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve in rats was selected as neuropathic pain model. Mechanical hypersensitivity and depression-like behaviour were evaluated 4 weeks after surgery by "electronic algometer" and forced swimming test (FST), which measured the time of immobility, and active behaviours climbing and swimming. The selective noradrenergic and serotonergic uptake blocker duloxetine (20mg/kg) and the selective 5-HT1A agonist 8-OH-DPAT (0.5mg/kg) significantly reversed both mechanical hypersensitivity and depression-like behaviour in CCI animals. Duloxetine significantly reversed depression-like behaviour in CCI rats by increasing the time of climbing and swimming, while 8-OH-DPAT attenuated depression-like behaviour mainly by increasing the time of swimming. However, the selective serotonergic uptake blocker fluoxetine (20mg/kg) failed to attenuate mechanical hypersensitivity and depression-like behaviour, possibly due to confounding pro-nociceptive actions at 5-HT3 receptors. These data suggest to target noradrenergic and 5-HT1A receptors for treatment of chronic pain and its comorbidity depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats.

    Science.gov (United States)

    Caspani, Ombretta; Reitz, Marie-Céline; Ceci, Angelo; Kremer, Andreas; Treede, Rolf-Detlef

    2014-09-01

    Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (Ppain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Holistic approach to treatment of intractable central neuropathic itch.

    Science.gov (United States)

    Curtis, Ashley R; Tegeler, Charles; Burdette, Jonathan; Yosipovitch, Gil

    2011-05-01

    Central neuropathic itch can be a lifelong debilitating condition and treatment challenge. We report a patient with a traumatic brain injury with severe intractable pruritus who failed extensive pharmacologic and nonpharmacologic treatment but responded to a holistic approach using healing touch. We discuss the complexity of this type of neuropathic itch and present a holistic approach as an adjunct to therapy in reducing itch intensity. This case presentation along with the literature discussed suggests a therapeutic strategy for the management of complicated central neuropathic itch. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  14. Oxcarbazepine for neuropathic pain.

    Science.gov (United States)

    Zhou, Muke; Chen, Ning; He, Li; Yang, Mi; Zhu, Cairong; Wu, Fengbo

    2017-12-02

    Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has been reported to be efficacious in the treatment of neuropathic pain, but evidence from randomised controlled trials (RCTs) is conflicting. Oxcarbazepine is reportedly better tolerated than carbamazepine. This is the first update of a review published in 2013. To assess the benefits and harms of oxcarbazepine for different types of neuropathic pain. On 21 November 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We searched the Chinese Biomedical Retrieval System (January 1978 to November 2016). We searched the US National Institutes of Health (NIH) databases and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials in January 2017, and we wrote to the companies who make oxcarbazepine and to pain experts requesting additional information. All RCTs and randomised cross-over studies of oxcarbazepine for the treatment of people of any age or sex with any neuropathic pain were eligible. We planned to include trials of oxcarbazepine compared with placebo or any other intervention with a treatment duration of at least six weeks, regardless of administration route and dose. We used standard methodological procedures expected by Cochrane. Five multicentre, randomised, placebo-controlled, double-blind trials with a total of 862 participants were eligible for inclusion in this updated review. Three trials involved participants with painful diabetic peripheral neuropathy (DPN) (n = 634), one included people with neuropathic pain due to radiculopathy (n = 145), and one, which was newly identified at this update, involved participants with peripheral neuropathic pain of mixed origin (polyneuropathy, peripheral nerve injury or postherpetic neuralgia) (n = 83). Some studies did not report all outcomes of interest. For

  15. Topical amitriptyline and ketamine for the treatment of neuropathic pain.

    Science.gov (United States)

    Mercadante, Sebastiano

    2015-01-01

    A neuropathy is a disturbance of function or pathological change in nerves. In some cases, peripheral neuropathic pain may occur due to a lesion or disease of the peripheral somatosensory nervous system. Efficacy of different agents for peripheral neuropathic pain conditions is less than optimal. The administration of topical analgesics might be an option, due to the potential of reduced adverse effects and increased patient compliance. There is major interest in compounding topical analgesics for peripheral neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of peripheral neuropathic pain. Topical amitriptyline-ketamine combination (AK) is a promising agent for peripheral neuropathic pain conditions. Some studies have shown its efficacy in neuropathic pain conditions. However, this data was not uniformely obtained and its role remains still controversial. Efficacy may depend on many factors, including the choice of the vehicle, the concentration, the pain site, and specific diseases. More studies are necessary to support the use of AK in clinical practice.

  16. Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages

    Directory of Open Access Journals (Sweden)

    Norikazu Kiguchi

    2017-11-01

    Full Text Available Neuropathic pain can have a major effect on quality of life but current therapies are often inadequate. Growing evidence suggests that neuropathic pain induced by nerve damage is caused by chronic inflammation. Upon nerve injury, damaged cells secrete pro-inflammatory molecules that activate cells in the surrounding tissue and recruit circulating leukocytes to the site of injury. Among these, the most abundant cell type is macrophages, which produce several key molecules involved in pain enhancement, including cytokines and chemokines. Given their central role in the regulation of peripheral sensitization, macrophage-derived cytokines and chemokines could be useful targets for the development of novel therapeutics. Inhibition of key pro-inflammatory cytokines and chemokines prevents neuroinflammation and neuropathic pain; moreover, recent studies have demonstrated the effectiveness of pharmacological inhibition of inflammatory (M1 macrophages. Nicotinic acetylcholine receptor ligands and T helper type 2 cytokines that reduce M1 macrophages are able to relieve neuropathic pain. Future translational studies in non-human primates will be crucial for determining the regulatory mechanisms underlying neuroinflammation-associated neuropathic pain. In turn, this knowledge will assist in the development of novel pharmacotherapies targeting macrophage-driven neuroinflammation for the treatment of intractable neuropathic pain.

  17. 8-O-Acetyl Shanzhiside Methylester From Lamiophlomis Rotata Reduces Neuropathic Pain by Inhibiting the ERK/TNF-α Pathway in Spinal Astrocytes

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2018-03-01

    Full Text Available Lamiophlomis rotata (L. rotata; Benth. Kudo is an effective traditional herb in the clinical treatment of chronic pain syndromes in China. 8-O-acetyl shanzhiside methylester (8-OaS, a chief component in L. rotata, possesses potent immunosuppressive activities and favorable analgesic effects. This study was proposed to compare the analgesic effects of 8-OaS with those of lidocaine and ketamine in a spinal nerve ligation (SNL model by behavioral tests, and then investigated its effects upon the expression of spinal glial fibrillary acidic protein (GFAP, phosphorylated extracellular regulated protein kinases (pERK and tumor necrosis factor-alpha (TNF-α via immunofluorescence staining and western blot analyses. The data showed consecutive intrathecal injection of 8-OaS for 2 weeks brought about remarkable palliation of neuropathic pain (NP, possessing similar anti-allodynia effects with those of lidocaine and ketamine. Two weeks after surgery, pERK within the spinal dorsal horn was mainly expressed in astrocytes more than neurons and microglia, and 8-OaS inhibited spinal astrocytic activation and TNF-α expression. Finally, co-treatment of 8-OaS and PD98059 (an Extracellular signal-regulated kinase, ERK inhibitor did not lead to remarkable increase in pain relief or TNF-α expression comparing to rats treated with 8-OaS or PD98059 alone. In conclusion, the anti-nociceptive effects of 8-OaS in the condition of NP relied on the inhibition of SNL-induced astrocyte activation, probably via the down-regulation of the ERK/TNF-α pathway.

  18. Neuropathic pain management in children.

    LENUS (Irish Health Repository)

    Hyde, Catherine

    2012-10-01

    There are difficulties in assessing, managing, and evaluating neuropathic pain in dying children, particularly those with neurological impairment. Neuropathic pain in children often presents differently to how it presents in the adult population. Comprehensive assessment as well as pharmacological and non-pharmacological interventions are crucial to its successful management and frequently require input from an interdisciplinary team. Notwithstanding the need for further research, this paper brings together research papers, reviews, and clinical guidelines to present an exploration of existing evidence regarding care for children with neuropathic pain and their families.

  19. Neuropathic pain and dry eye.

    Science.gov (United States)

    Galor, Anat; Moein, Hamid-Reza; Lee, Charity; Rodriguez, Adriana; Felix, Elizabeth R; Sarantopoulos, Konstantinos D; Levitt, Roy C

    2018-01-01

    Dry eye is a common, multifactorial disease currently diagnosed by a combination of symptoms and signs. Its epidemiology and clinical presentation have many similarities with neuropathic pain outside the eye. This review highlights the similarities between dry eye and neuropathic pain, focusing on clinical features, somatosensory function, and underlying pathophysiology. Implications of these similarities on the diagnosis and treatment of dry eye are discussed. Published by Elsevier Inc.

  20. Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2014-01-01

    Full Text Available Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

  1. Puerarin alleviates neuropathic pain by inhibiting neuroinflammation in spinal cord.

    Science.gov (United States)

    Liu, Ming; Liao, Kaijun; Yu, Changxi; Li, Xuejun; Liu, Suhuan; Yang, Shuyu

    2014-01-01

    Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4-100 nM) for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB) and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

  2. [Management of neuropathic pain].

    Science.gov (United States)

    Lozeron, P; Kubis, N

    2015-07-01

    Neuropathic pain is often underestimated and not adequately treated. The DN4 scale is very useful for its identification since it will benefit from pharmacological and non-pharmacological specific alternative care. The pathophysiological mechanisms involve the hyperexcitability of nociceptive pathways or decreased inhibitory descending controls that will be the target of pharmacological treatments. Frontline molecules are antidepressants (tricyclics and mixed serotonin and norepinephrine reuptake inhibitors) and antiepileptics (α2δ calcium channel inhibitors). However, these drugs will only have a partial efficacy on pain. The therapeutic strategy is based on reasonable goals, starting with a monotherapy adapted to the patient's symptoms and comorbidities and increased step by step. Patient compliance to contract is essential and requires clear and complete information. The impact on profession, social and family integration should rapidly be taken into account. In case of inefficiency, a change of the first-line treatment or an association could be considered. Some indications justify a specific therapy. Patients with resistant chronic pain should be sent to a specialized centre. New drugs are being studied and non-pharmacological support must be evaluated. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  3. The effect of Sativex in neuropathic pain and spasticity in spinal cord injury

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Hansen, Rikke Bod Middelhede; Johansen, Inger Lauge

    2014-01-01

    Introduction: Neuropathic pain and spasticity after spinal cord injury represent significant but still unresolved problems, which cause considerable suffering and reduced quality of life for patients with spinal cord injury. Treatment of neuropathic pain and spasticity is complicated and patients...... often receive incomplete relief from present available and recommended treatment. Cannabinoids has shown efficacy on both neuropathic pain and spasticity in patients with spinal cord injury, but the studies one the topic has been too small to make a general conclusion for patients with spinal cord...... injury. Aims: To investigate the effect of Sativex (cannabinoid agonist given as an oral mucosal spray), on neuropathic pain and spasticity in patients with spinal cord injury. Methods: A randomized, double-blind, placebo-controlled crossover study. We will include 30 patients with neuropathic pain...

  4. Pharmacologic management of neuropathic pain.

    Science.gov (United States)

    Gordon, Debra B; Love, Georgette

    2004-12-01

    The mechanisms underlying the pathogenesis of neuropathic pain are complex but are gradually coming to light. Agents that have been found effective in a variety of neuropathic pain conditions include drugs that act to modulate (a) sodium or calcium channels, (b) N-methyl-D-aspartate receptors, (c) norepinephrine or serotonin reuptake, (d) opioid receptors, and (e) other cellular processes. Clinical trials have primarily evaluated these treatments for postherpetic neuralgia and painful diabetic neuropathy, the two most common types of neuropathic pain. Nonetheless, the identification of effective treatment regimens remains challenging, often because multiple mechanisms may be operating in a given patient giving rise to the same symptom. Alternatively, a single mechanism may be responsible for multiple symptoms. Currently available diagnostic tools are inadequate to determine the best treatment using a mechanism-based model. Clinically, drug treatment of neuropathic pain is often a matter of treatment trials. This article presents a summary of available clinical information on first-line and lesser-known treatments for neuropathic pain.

  5. Benfotiamine relieves inflammatory and neuropathic pain in rats.

    Science.gov (United States)

    Sánchez-Ramírez, Gabriela M; Caram-Salas, Nadia L; Rocha-González, Héctor I; Vidal-Cantú, Guadalupe C; Medina-Santillán, Roberto; Reyes-García, Gerardo; Granados-Soto, Vinicio

    2006-01-13

    Benfotiamine has shown therapeutic efficacy in the treatment of painful diabetic neuropathy in human beings. However, so far there is no evidence about the efficacy of this drug in preclinical models of pain. The purpose of this study was to assess the possible antinociceptive and antiallodynic effect of benfotiamine in inflammatory and neuropathic pain models in the rat. Inflammatory pain was induced by injection of formalin in non-diabetic and diabetic (2 weeks) rats. Reduction of flinching behavior was considered as antinociception. Neuropathic pain was induced by either ligation of left L5/L6 spinal nerves or administration of streptozotocin (50 mg/kg, i.p.) in Wistar rats. Benfotiamine significantly reduced inflammatory (10-300 mg/kg) and neuropathic (75-300 mg/kg) nociception in non-diabetic and diabetic rats. Results indicate that oral administration of benfotiamine is able to reduce tactile allodynia from different origin in the rat and they suggest the use of this drug to reduce inflammatory and neuropathic pain in humans.

  6. Combination treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Holbech, Jakob Vormstrup; Jung, Anne; Jonsson, Torsten

    2017-01-01

    BACKGROUND: Current Danish treatment algorithms for pharmacological treatment of neuropathic pain (NeP) are tricyclic antidepressants (TCA), gabapentin and pregabalin as first-line treatment for the most common NeP conditions. Many patients have insufficient pain relief on monotherapy, but combin...

  7. Neuropathic pain in leprosy: symptom profile characterization and comparison with neuropathic pain of other etiologies.

    Science.gov (United States)

    Raicher, Irina; Stump, Patrick Raymond Nicolas Andre Ghislain; Harnik, Simone Bega; de Oliveira, Rodrigo Alves; Baccarelli, Rosemari; Marciano, Lucia H S C; Ura, Somei; Virmond, Marcos C L; Teixeira, Manoel Jacobsen; de Andrade, Daniel Ciampi

    2018-03-01

    Previous studies reported a high prevalence of neuropathic pain in leprosy, being especially present in "pharmacologically cured" patients. The presence of neuropathic pain in leprosy poses a supplementary burden in patient's quality of life, daily activities, and mood. The aim of this study was to assess whether neuropathic pain in leprosy has similar symptom profile as neuropathic pain of other etiologies and to retrospectively assess the efficacy of neuropathic pain medications regularly prescribed to leprosy. Leprosy and nonleprosy patients had their neuropathic pain characterized by the neuropathic pain symptom inventory (NPSI, ranges from 0 to 100, with 100 being the maximal neuropathic pain intensity) in a first visit. In a second visit, leprosy patients who had significant pain and received pharmacological treatment in the first evaluation were reassessed (NPSI) and had their pain profile and treatment response further characterized, including information on drugs prescribed for neuropathic pain and their respective pain relief. The pain characteristics based on NPSI did not significantly differ between leprosy and nonleprosy neuropathic pain patients in visit 1 after correction for multiple analyses, and cluster analyses confirmed these findings (ie, no discrimination between leprosy and nonleprosy groups; Pearson χ2 = 0.072, P = 0.788). The assessment of pain relief response and the drugs taken by each patient, linear regression analysis showed that amitriptyline, when effective, had the highest percentage of analgesic relief. Neuropathic pain in leprosy is as heterogeneous as neuropathic pain of other etiologies, further supporting the concept that neuropathic pain is a transetiological entity. Neuropathic pain in leprosy may respond to drugs usually used to control pain of neuropathic profile in general, and amitriptiline may constitute a potential candidate drug for future formal clinical trials aimed at controlling neuropathic pain in leprosy.

  8. Antinociception induced by rosuvastatin in murine neuropathic pain.

    Science.gov (United States)

    Miranda, Hugo F; Sierralta, Fernando; Aranda, Nicolas; Poblete, Paula; Castillo, Rodrigo L; Noriega, Viviana; Prieto, Juan Carlos

    2018-06-01

    Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1β, TBARS and glutathione were evaluated. A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1β, glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL murine models. PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1β or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia. The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain. Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  9. Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Gui-Lin Jin

    2018-01-01

    Full Text Available Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.

  10. Spinal Gap Junction Channels in Neuropathic Pain

    OpenAIRE

    Jeon, Young Hoon; Youn, Dong Ho

    2015-01-01

    Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced...

  11. Cortical stimulation and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Cristiane Cagnoni Ramos

    2015-02-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2015v28n2p1 This paper is a review of physiological and behavioral data on motor cortex stimulation (MCS and its role in persistent neuropathic pain. MCS has been widely used in clinical medicine as a tool for the management of pain that does not respond satisfactorily to any kind of conventional analgesia. Some important mechanisms involved in nociceptive modulation still remains unclear. The aim of this study was to describe the mechanisms involved in neuropathic pain and introduce the effectiveness of electrical stimulation of the motor cortex used in the treatment of this disease. The ascending pain pathways are activated by peripheral receptors, in which there is the transduction of a chemical, physical or mechanical stimulus as a nerve impulse, where this impulse is transmitted to the dorsal horn of the spinal cord, which connects with second-order neurons and ascends to different locations in the central nervous system where the stimulus is perceived as pain. Because MCS has been proved to modulate this pathway in the motor cortex, it has been studied to mimic its effects in clinical practice and improve the treatments used for chronic pain. MCS has gained much attention in recent years due to its action in reversing chronic neuropathic pain, this being more effective than electrical stimulation at different locations and related pain nuclei.

  12. Cortical stimulation and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Cristiane Cagnoni Ramos

    2015-05-01

    Full Text Available This paper is a review of physiological and behavioral data on motor cortex stimulation (MCS and its role in persistent neuropathic pain. MCS has been widely used in clinical medicine as a tool for the management of pain that does not respond satisfactorily to any kind of conventional analgesia. Some important mechanisms involved in nociceptive modulation still remains unclear. The aim of this study was to describe the mechanisms involved in neuropathic pain and introduce the effectiveness of electrical stimulation of the motor cortex used in the treatment of this disease. The ascending pain pathways are activated by peripheral receptors, in which there is the transduction of a chemical, physical or mechanical stimulus as a nerve impulse, where this impulse is transmitted to the dorsal horn of the spinal cord, which connects with second-order neurons and ascends to different locations in the central nervous system where the stimulus is perceived as pain. Because MCS has been proved to modulate this pathway in the motor cortex, it has been studied to mimic its effects in clinical practice and improve the treatments used for chronic pain. MCS has gained much attention in recent years due to its action in reversing chronic neuropathic pain, this being more effective than electrical stimulation at different locations and related pain nuclei.

  13. In vitro study of the neuropathic potential of the organophosphorus compounds fenamiphos and profenofos: Comparison with mipafox and paraoxon.

    Science.gov (United States)

    Emerick, Guilherme L; Fernandes, Laís S; de Paula, Eloísa Silva; Barbosa, Fernando; dos Santos, Neife Aparecida Guinaim; dos Santos, Antonio Cardozo

    2015-08-01

    Organophosphorus-induced delayed neuropathy (OPIDN) is a central-peripheral distal axonopathy that develops 8-14 days after poisoning by a neuropathic organophosphorus compound (OP). Several OPs that caused OPIDN were withdrawn from the agricultural market due to induction of serious delayed effects. Therefore, the development of in vitro screenings able to differentiate neuropathic from non-neuropathic OPs is of crucial importance. Thus, the aim of this study was to evaluate the differences in the neurotoxic effects of mipafox (neuropathic OP) and paraoxon (non-neuropathic OP) in SH-SY5Y human neuroblastoma cells, using the inhibition and aging of neuropathy target esterase (NTE), inhibition of acetylcholinesterase (AChE), activation of calpain, neurite outgrowth, cytotoxicity and intracellular calcium as indicators. Additionally, the potential of fenamiphos and profenofos to cause acute and/or delayed effects was also evaluated. Mipafox had the lowest IC50 and induced the highest percentage of aging of NTE among the OPs evaluated. Only mipafox was able to cause calpain activation after 24 h of incubation. Concentrations of mipafox and fenamiphos which inhibited at least 70% of NTE were also able to reduce neurite outgrowth. Cytotoxicity was higher in non-neuropathic than in neuropathic OPs while the intracellular calcium levels were higher in neuropathic than in non-neuropathic OPs. In conclusion, the SH-SY5Y cellular model was selective to differentiate neuropathic from non-neuropathic OPs; fenamiphos, but not profenofos presented results compatible with the induction of OPIDN. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Pharmacologic management of chronic neuropathic pain

    Science.gov (United States)

    Mu, Alex; Weinberg, Erica; Moulin, Dwight E.; Clarke, Hance

    2017-01-01

    Abstract Objective To provide family physicians with a practical clinical summary of the Canadian Pain Society (CPS) revised consensus statement on the pharmacologic management of neuropathic pain. Quality of evidence A multidisciplinary interest group within the CPS conducted a systematic review of the literature on the current treatments of neuropathic pain in drafting the revised consensus statement. Main message Gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are the first-line agents for treating neuropathic pain. Tramadol and other opioids are recommended as second-line agents, while cannabinoids are newly recommended as third-line agents. Other anticonvulsants, methadone, tapentadol, topical lidocaine, and botulinum toxin are recommended as fourth-line agents. Conclusion Many pharmacologic analgesics exist for the treatment of neuropathic pain. Through evidence-based recommendations, the CPS revised consensus statement helps guide family physicians in the management of patients with neuropathic pain. PMID:29138154

  15. Neuropathic pain in spinal cord injury.

    Science.gov (United States)

    Nakipoglu-Yuzer, Guidal F; Atçı, Nermin; Ozgirgin, Nese

    2013-01-01

    Several studies have described pain prevalence, risk factors, pain and medical variables in spinal cord injury (SCI) populations. In this study on traumatic SCI in Turkey, we surveyed the neuropathic pain experiences during in-patient rehabilitation and defined the relationships between neuropathic pain and demographic and SCI characteristics of patients. To survey the neuropathic pain experiences during in-patient rehabilitation in traumatic SCI and to define the relationships between neuropathic pain and demographic and SCI-related characteristics of patients. Descriptive study. Physicial Medicine and Rehabilitation inpatient clinic, Ankara, Turkey Sixty-nine SCI patients as inpatients were included in this descriptive study. All patients demographic and SCI-related characteristics were enrolled. The diagnosis of neuropathic pain was made with the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale. Location of pain and pain description, relation to time and severity according to McGill Pain Questionnaire (MPQ) were enrolled. The neuropathic pain localization was below the lesion level in 67 (97.1%) and at the lesion level in 2 (2.9%) patients. The pain was at the hip and leg regions in 36 (52.2%) patients. The neuropathic pain was defined as burning in 27 (39.1%), aching in 26 (37.7%), sharp in 4 (5.8%), stinging in 3 (4.3%), and cramping in 3 (4.3%). We did not find a significant difference between demographic and SCI-related characteristics and the localization of neuropathic pain for the patients (P > 0.05). There was no significant difference according to pain description by MPQ and pain localization (P > 0.05). We found a significant relationship between the patient's lesion level and the region of pain (P neuropathic pain due to SCI to be mostly below the lesion level with a burning or aching character and we did not find a significant relationship between the demographic and SCI-related characteristics of the patient and the pain

  16. Animal model of neuropathic tachycardia syndrome

    Science.gov (United States)

    Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

    2001-01-01

    Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

  17. Interventional therapy for neuropathic pain

    Directory of Open Access Journals (Sweden)

    YANG Yang

    2013-10-01

    Full Text Available Neuropathic pain (NP is a common clinical refractory pain for which there are limited methods to treat. In this article, based on typical diseases, such as postherpetic neuralgia (PHN, trigeminal neuralgia, complex regional pain syndrome (CRPS, lower back pain with radiculopathy and failed back surgery syndrome (FBSS, phantom pain, the general treatment principle and method for NP are expatiated. Interventional methods for NP, including intraspinal block, radiofrequeney rhizotomy of trigeminal neuralgia, selective nerve root block, spinal cord stimulation (SCS and motor cortex stimulation (MCS are introduced, especially their indications, complications and matters needing attention.

  18. Analgesic Microneedle Patch for Neuropathic Pain Therapy.

    Science.gov (United States)

    Xie, Xi; Pascual, Conrado; Lieu, Christopher; Oh, Seajin; Wang, Ji; Zou, Bende; Xie, Julian; Li, Zhaohui; Xie, James; Yeomans, David C; Wu, Mei X; Xie, Xinmin Simon

    2017-01-24

    Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

  19. The neurosurgical treatment of neuropathic facial pain.

    Science.gov (United States)

    Brown, Jeffrey A

    2014-04-01

    This article reviews the definition, etiology and evaluation, and medical and neurosurgical treatment of neuropathic facial pain. A neuropathic origin for facial pain should be considered when evaluating a patient for rhinologic surgery because of complaints of facial pain. Neuropathic facial pain is caused by vascular compression of the trigeminal nerve in the prepontine cistern and is characterized by an intermittent prickling or stabbing component or a constant burning, searing pain. Medical treatment consists of anticonvulsant medication. Neurosurgical treatment may require microvascular decompression of the trigeminal nerve. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. AAPT Diagnostic Criteria for Central Neuropathic Pain

    DEFF Research Database (Denmark)

    Widerstrom-Noga, Eva; Loeser, John D.; Jensen, Troels Staehelin

    2017-01-01

    Central neuropathic pain, which is pain caused by a lesion or disease of the central somatosensory nervous system, is a serious consequence of spinal cord injury, stroke, multiple sclerosis, and other conditions affecting the central nervous system. A collaborative effort between the Analgesic....... This article focuses on central neuropathic pain associated with spinal cord injury, stroke, and multiple sclerosis, but the AAPT framework can be extended to central pain due to other causes such as traumatic brain injury. The classification of central neuropathic pain is organized according to the AAPT...

  1. PHARMACOTHERAPY IN ELDERLY NEUROPATHIC PAIN

    Directory of Open Access Journals (Sweden)

    Thomas Eko P

    2013-10-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 The incidence of pain increases with age. Neuropathic pain are common in elderly patients and pose challenges in both their diagnosis and treatment. The most common neuropathic pain in elderly are radiculopathy due to foraminal or spinal stenosis, diabetic neuropathy, and postherpetic neuralgia. Pain in the elderly is often unrecognized and undertreated. The main problem with pain in older adults relates to impaired quality of life secondary to pain which may be expressed by depression (including increased suicide risk, anxiety, sleep disruption, appetite disturbance, and weight loss, cognitive impairment, and limitations in the performance of daily activities. Pain management in elderly patients requires a different perspective from that of younger patients. Causes, comorbidities, and responses to both pain and its treatment differ between young healthy and older patients. Effective pain management in elderly patients should include both pharmacologic and nonpharmacologic strategies. Pharmacological approaches are the first line of pain management in older person for neuropathic pain. Pharmacologic strategies call for administration of nonopioid analgesics, opioid analgesics, and adjuvant medication. Polypharmacy, drug-drug and drug-disease interactions, age-associated changes in drug metabolism, and the high frequency of adverse drug reactions need to be carefully considered in using medications in this population /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso

  2. Total contact cast for neuropathic diabetic foot ulcers

    International Nuclear Information System (INIS)

    Ali, R.; Yaqoob, M.Y.

    2008-01-01

    To determine the outcome of diabetic neuropathic foot ulcers treated with Total Contact Cast (TCC) in terms of percentage of ulcers healed and time to heal. The study included diabetic patients with non-ischemic neuropathic foot ulcers of upto grade 2 of Wagner's classification. Ulcers were debrided off necrotic tissues and Total Contact Cast (TCC) was applied. TCC was renewed every 2 weeks till healing. Cases were labeled as cast failure when there was no reduction in wound size in 4 consecutive weeks or worsening to a higher grade. Main outcome measures were the percentage of ulcers healed and time to heal in the cast. Thirty four (87.17%) patients were males and 5(12.82%) were females. The mean age was 62 +- 13.05 years. All patients had NIDDM. Out of the 52 ulcers, 41(78.84%) healed with TCC in an average 2 casts duration (mean 32 days). There were 11(21.15%) cast failure. Majority (63.63%) of cast failure ulcers were located on pressure bearing area of heel. Most (90%) of the ulcers on forefoot and midsole region healed with TCC (p<0.001). Longer ulcer duration (mean 57.45 +- 29.64 days) significantly reduced ulcer healing (p<0.001). Total contact cast was an effective treatment modality for neuropathic diabetic foot ulcers of Wagner's grade 2, located on forefoot and midsole region. (author)

  3. Neuropathic pain: targeting the melatonin MT receptor

    African Journals Online (AJOL)

    inflammatory drugs (NSAIDs) and opioids is highly effective in ... to drug treatment. .... effects in chronic neuropathic pain, which are mediated by the .... Reiter R, Tan D, Kim S, Cruz M. Delivery of pineal melatonin to the brain and SCN:.

  4. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Otto, Marit; Finnerup, Nanna Brix

    2005-01-01

    Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit...... presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated...... in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral...

  5. Neuropathic low back pain in clinical practice.

    Science.gov (United States)

    Baron, R; Binder, A; Attal, N; Casale, R; Dickenson, A H; Treede, R-D

    2016-07-01

    Low back pain (LBP) is one of the most common chronic pain conditions. This paper reviews the available literature on the role of neuropathic mechanisms in chronic LBP and discusses implications for its clinical management, with a particular focus on pharmacological treatments. Literature searches were performed in PubMed, key pain congresses and ProQuest Dialog to identify published evidence on neuropathic back pain and its management. All titles were assessed for relevant literature. Chronic LBP comprises both nociceptive and neuropathic components, however, the neuropathic component appears under-recognized and undertreated. Neuropathic pain (NP) is challenging to manage. Many patients with chronic LBP have pain that is refractory to existing treatments. Typically, less than half of patients experience clinically meaningful analgesia with oral pharmacotherapies; these are also associated with risks of adverse effects. Paracetamol and NSAIDs, although widely used for LBP, are unlikely to ameliorate the neuropathic component and data on the use of NP medications such as antidepressants and gabapentin/pregabalin are limited. While there is an unmet need for improved treatment options, recent data have shown tapentadol to have efficacy in the neuropathic component of LBP, and studies suggest that the capsaicin 8% patch and lidocaine 5% medicated plaster, topical analgesics available for the treatment of peripheral NP, may be a valuable additional approach for the management of neuropathic LBP. Chronic LBP often has an under-recognized neuropathic component, which can be challenging to manage, and requires improved understanding and better diagnosis and treatment. WHAT DOES THIS REVIEW ADD?: Increased recognition and improved understanding of the neuropathic component of low back pain raises the potential for the development of mechanism-based therapies. Open and retrospective studies suggest that agents like tapentadol and topical analgesics - such as the capsaicin

  6. Hindfoot Arthrodesis for Neuropathic Deformity

    Directory of Open Access Journals (Sweden)

    Peng-Ju Huang

    2007-03-01

    Full Text Available Acquired neurologic disorders of the foot lead to arthrosis, deformities, instabilities, and functional disabilities. Hindfoot arthrodesis is the current option available for irreducible or nonbraceable deformities of neuropathic feet. However, the role of ankle arthrodesis in these patients has been questioned because of high nonunion and complication rates. From 1990 to 2001, 17 cases of acquired neuropathic foot deformities were treated by four tibiotalocalcaneal (TTC arthrodeses and 13 ankle arthrodeses. TTC arthrodesis was performed on cases with combined ankle and subtalar arthritis or cases whose deformities or instabilities could not be corrected by ankle fusion alone. There was no nonunion of TTC arthrodesis and seven ununited ankle arthrodeses were salvaged by two TTC-attempted arthrodeses and five revision ankle-attempted arthrodeses. Eventually in these cases, there was one nonunion in TTC arthrodesis and one nonunion in revision ankle arthrodesis. The final fusion rate was 88% (15 of 17 cases with average union time of 6.9 months (range, 2.5–18 months. The American Orthopaedic Foot and Ankle Society ankle hind-foot functional scores were evaluated: one was excellent (5.8%, seven were good (41%, eight were fair (53.3%, and one was poor (5.8% in terms of total functional outcome. We conclude that TTC arthrodesis is indicated for cases with ankle and subtalar involvement and ankle arthrodesis is an alternative for cases with intact subtalar joint. We recommend revision ankle arthrodesis if the ankle fails to fuse and the bone stock of the talus is adequate. TTC arthrodesis is reserved for ankles with poor bone stock of the talus with fragmentation.

  7. Molecular Hydrogen Attenuates Neuropathic Pain in Mice

    Science.gov (United States)

    Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei

    2014-01-01

    Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting. PMID:24941001

  8. Neuropathic pain due to fibromatosis: Does anticancer treatment help?

    Directory of Open Access Journals (Sweden)

    David Mathew

    2011-01-01

    Full Text Available Desmoid fibromatosis, although histologically benign, infiltrates local structures. The involvement of neural structures can lead to difficult neuropathic pain and the escalating use of analgesics. We report a patient with desmoid fibromatosis of the chest wall causing brachial plexus infiltration. As the tumor was locally invasive and unresectable, he was treated with radiation therapy and oral tamoxifen. On follow-up, there was significant pain relief, sustained reduction in the tumor size, and reduced analgesic requirement. Antineoplastic treatments like local radiation therapy and targeted systemic therapy with hormones or other agents can be considered in the management of selected unresectable desmoid fibromatosis to improve symptom control and reduce polypharmacy.

  9. HIV Distal Neuropathic Pain Is Associated with Smaller Ventral Posterior Cingulate Cortex.

    Science.gov (United States)

    Keltner, John R; Connolly, Colm G; Vaida, Florin; Jenkinson, Mark; Fennema-Notestine, Christine; Archibald, Sarah; Akkari, Cherine; Schlein, Alexandra; Lee, Jisu; Wang, Dongzhe; Kim, Sung; Li, Han; Rennels, Austin; Miller, David J; Kesidis, George; Franklin, Donald R; Sanders, Chelsea; Corkran, Stephanie; Grant, Igor; Brown, Gregory G; Atkinson, J Hampton; Ellis, Ronald J

    2017-03-01

    . Despite modern antiretroviral therapy, HIV-associated neuropathy is one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of distal neuropathic pain is not fully explained by the degree of peripheral nerve damage. A better understanding of brain structure in HIV distal neuropathic pain may help explain why some patients with HIV neuropathy report pain while the majority does not. Previously, we reported that more intense distal neuropathic pain was associated with smaller total cerebral cortical gray matter volumes. The objective of this study was to determine which parts of the cortex are smaller. . HIV positive individuals with and without distal neuropathic pain enrolled in the multisite (N = 233) CNS HIV Antiretroviral Treatment Effects (CHARTER) study underwent structural brain magnetic resonance imaging. Voxel-based morphometry was used to investigate regional brain volumes in these structural brain images. . Left ventral posterior cingulate cortex was smaller for HIV positive individuals with versus without distal neuropathic pain (peak P  = 0.017; peak t = 5.15; MNI coordinates x = -6, y = -54, z = 20). Regional brain volumes within cortical gray matter structures typically associated with pain processing were also smaller for HIV positive individuals having higher intensity ratings of distal neuropathic pain. . The posterior cingulate is thought to be involved in inhibiting the perception of painful stimuli. Mechanistically a smaller posterior cingulate cortex structure may be related to reduced anti-nociception contributing to increased distal neuropathic pain. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  10. Melatonin limits paclitaxel‐induced mitochondrial dysfunction in vitro and protects against paclitaxel‐induced neuropathic pain in the rat

    OpenAIRE

    Galley, Helen F.; McCormick, Barry; Wilson, Kirsten L.; Lowes, Damon A.; Colvin, Lesley; Torsney, Carole

    2017-01-01

    Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment. Mitochondrial dysfunction associated with oxidative stress in peripheral nerves has been implicated in the underlying mechanism. We investigated the potential of melatonin, a potent antioxidant that preferentially acts within mitochondria, to reduce mitochondrial damage and neuropathic pain resulting from the chemotherapeutic drug paclitaxel. In vitro, paclitaxel caused a 50% reduction of mitoc...

  11. A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons

    Science.gov (United States)

    Zhao, Xiuli; Tang, Zongxiang; Zhang, Hongkang; Atianjoh, Fidelis E.; Zhao, Jian-Yuan; Liang, Lingli; Wang, Wei; Guan, Xiaowei; Kao, Sheng-Chin; Tiwari, Vinod; Gao, Yong-Jing; Hoffman, Paul N.; Cui, Hengmi; Li, Min; Dong, Xinzhong; Tao, Yuan-Xiang

    2013-01-01

    Neuropathic pain is a refractory disease characterized by maladaptive changes in gene transcription and translation within the sensory pathway. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the development of neuropathic pain is unclear. Here we identify a conserved lncRNA for Kcna2 (named Kcna2 antisense RNA) in first-order sensory neurons of rat dorsal root ganglion (DRG). Peripheral nerve injury increases Kcna2 antisense RNA expression in injured DRG through activation of myeloid zinc finger protein 1, a transcription factor that binds to Kcna2 antisense RNA gene promoter. Mimicking this increase downregulates Kcna2, reduces total Kv current, increases excitability in DRG neurons, and produces neuropathic pain symptoms. Blocking this increase reverses nerve injury-induced downregulation of DRG Kcna2 and attenuates development and maintenance of neuropathic pain. These findings suggest native Kcna2 antisense RNA as a new therapeutic target for the treatment of neuropathic pain. PMID:23792947

  12. Therapeutic implications of toll-like receptors in peripheral neuropathic pain.

    Science.gov (United States)

    Thakur, Krishan K; Saini, Jyoti; Mahajan, Kanika; Singh, Dhyanendra; Jayswal, Dinkar P; Mishra, Srishti; Bishayee, Anupam; Sethi, Gautam; Kunnumakkara, Ajaikumar B

    2017-01-01

    Neuropathic pain is a state of chronic pain arising after peripheral or central nerve injury. These injuries can be mediated through the activation of various cells (astrocytes, microglia and Schwann cells), as well as the dissolution of distal axons. Recent studies have suggested that after nerve injury, Toll-like receptors (TLRs) involved in Wallerian degeneration and generation of neuropathic pain. Furthermore, these TLRs are responsible for the stimulation of astrocytes and microglia that can cause induction of the proinflammatory mediators and cytokines in the spinal cord, thereby leading to the generation and maintenance of neuropathic pain. Indeed considering the prevalence of neuropathic pain and suffering of the affected patients, insights into the diverse mechanism(s) of activation of TLR signaling cascades may open novel avenues for the management of this chronic condition. Moreover, existing therapies like antidepressants, anticonvulsants, opiates and other analgesic are not sufficiently effective in reducing the pain. In this review, we present substantial evidences highlighting the diverse roles of TLRs and their signaling pathways involved in the progression of neuropathic pain. Furthermore, an elaborate discussion on various existing treatment regimens and future targets involving TLRs has also been included. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Neuropathic Pain Medication Use Does Not Alter Outcomes of Spinal Cord Stimulation for Lower Extremity Pain.

    Science.gov (United States)

    Maher, Dermot P; Martins, Yuri Chaves; Doshi, Tina; Bicket, Mark; Zhang, Kui; Hanna, George; Ahmed, Shihab

    2018-01-01

    Spinal cord stimulation (SCS) for the treatment of lower extremity pain is believed to the result of increased activity in the descending inhibitory and decreased activity in the ascending excitatory tracts. Evidence suggests that the analgesia afforded by SCS may be altered using certain neuropathic pain medications that also modulate neurotransmitters in these sensory tracts. We hypothesize that neuropathic pain medications may alter the response to SCS therapy. One hundred and fifteen subjects undergoing SCS therapy for lower extremity pain were retrospectively examined. The pharmacologic profile, including stable use of neuropathic and opioid medications, were recorded. Three separate logistic regression models examined the odds ratio of primary outcomes; a successful SCS trial, a 50% decrease in pain or a 50% reduction in opioid use one year after implant. Neither the use of opioids or neuropathic pain medications were associated with changes in the odds of a successful SCS trial or a 50% pain reduction. A higher dose of chronic opioids use prior to a trial was associated with greater odds of having a 50% reduction in opioid use following implant. OR 1.02, 95% CI 1.01-1.02, p-value neuropathic pain medications did not change the odds of either a successful SCS trial, or of experiencing a 50% reduction in pain at one year. The association between higher opioid doses and greater odds of a 50% reduction in opioid use may be the reflective of SCS's ability to reduce opioid reliance in chronic pain patients. © 2017 International Neuromodulation Society.

  14. [Prevalence and aetiopathogenesis of neuropathic pain in elderly cancer patients].

    Science.gov (United States)

    Cabezón-Gutiérrez, Luis; Custodio-Cabello, Sara; Khosravi-Shahi, Parham

    2016-01-01

    The prevalence of neuropathic pain is difficult to estimate as most studies evaluating chronic pain do not differentiate neuropathic from nociceptive pain. There are only a few studies of neuropathic pain in the elderly, specifically in the oncology population. This article is a non-systematic review of the relevant evidence on the prevalence and aetiopathogenesis of neuropathic cancer pain in the elderly. Copyright © 2015 SEGG. Published by Elsevier Espana. All rights reserved.

  15. A Review of Neuropathic Pain: From Diagnostic Tests to Mechanisms

    OpenAIRE

    Truini, Andrea

    2017-01-01

    Neuropathic pain develops when the somatosensory nervous system is affected by a lesion or disease. Diagnostic tests aimed at assessing somatosensory afferent pathway damage are therefore useful for diagnosing neuropathic pain. Neuropathic pain manifests with a range of different symptoms such as ongoing burning pain, squeezing or pressure pain, paroxysmal electric shock-like sensations, stabbing pain, or mechanical dynamic allodynia. The various types of neuropathic pain are associated with ...

  16. Central Neuropathic Pain in Spinal Cord Injury

    Science.gov (United States)

    Lee, Sujin; Zhao, Xing; Hatch, Maya; Chun, Sophia; Chang, Eric

    2015-01-01

    Spinal cord injury (SCI) is a devastating medical condition affecting 1.2 million people in the United States. Central neuropathic pain is one of the most common medical complications of SCI. Current treatment options include opioids, antiepileptic agents such as gabapentin, antispastic agents such as baclofen or tizanidine, and tricyclic acid. Other options include complementary, nonpharmacological treatment such as exercise or acupuncture, interventional treatments, and psychological approaches. Although these treatment options exist, central neuropathic pain in patients with SCI is still extremely difficult to treat because of its complexity. To develop and provide more effective treatment options to these patients, proper assessment of and classification tools for central neuropathic pain, as well as a better understanding of the pathophysiology, are needed. A combination of approaches, from standard general pain assessments to medically specific questions unique to SCI pathophysiology, is essential for this population. A multidisciplinary approach to patient care, in addition with a better understanding of pathophysiology and diagnosis, will lead to improved management and treatment of patients with SCI displaying central neuropathic pain. Here we summarize the most recent classification tools, pathophysiology, and current treatment options for patients with SCI with central neuropathic pain. PMID:25750485

  17. Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling

    Directory of Open Access Journals (Sweden)

    Enrique J. Cobos

    2018-01-01

    Full Text Available Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type.

  18. The effect of Normast (PEA) in neuropathic pain in spinal cord injury

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Bing, Jette; Hansen, Rikke Bod Middelhede

    2015-01-01

    Introduction: Neuropathic pain and spasticity after spinal cord injury represent significant problems. Palmitoylethanolamide (PEA) is a fatty acid that is produced in many cells in the body, and it is thought to potentiate the body's own cannabis-like substances (endocannabinoids). PEA is suggested...... to reduce pain and inflammation but randomized controlled trials are lacking. Normast is a medical supplement which contains (PEA) approved for use in Denmark. The primary aim is to investigate the effect of Normast (PEA) on neuropathic pain, and secondary to study the effect of Normast on spasticity...

  19. Estrogen alleviates neuropathic pain induced after spinal cord injury by inhibiting microglia and astrocyte activation.

    Science.gov (United States)

    Lee, Jee Youn; Choi, Hae Young; Ju, Bong-Gun; Yune, Tae Young

    2018-04-16

    Neuropathic pain after spinal cord injury (SCI) is developed in about 80% of SCI patients and there is no efficient therapeutic drug to alleviate SCI-induced neuropathic pain. Here we examined the effect of estrogen on SCI-induced neuropathic pain at below-level and its effect on neuroinflammation as underlying mechanisms. Neuropathic pain is developed at late phase after SCI and a single dose of 17β-estradiol (100, 300 μg/kg) were administered to rats with neuropathic pain after SCI through intravenous injection. As results, both mechanical allodynia and thermal hyperalgesia were significantly reduced by 17β-estradiol compared to vehicle control. Both microglia and astrocyte activation in the lamina I and II of L4-5 dorsal horn was also inhibited by 17β-estradiol. In addition, the levels of p-p38MAPK and p-ERK known to be activated in microglia and p-JNK known to be activated in astrocyte were significantly decreased by 17β-estradiol. Furthermore, the mRNA expression of inflammatory mediators such as Il-1β, Il-6, iNos, and Cox-2 was more attenuated in 17β-estradiol-treated group than in vehicle-treated group. Particularly, we found that the analgesic effect by 17β-estradiol was mediated via estrogen receptors, which are expressed in dorsal horn neurons. These results suggest that 17β-estradiol may attenuate SCI-induced neuropathic pain by inhibiting microglia and astrocyte activation followed inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Characteristics of neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Jang, Joon Young; Lee, Seung Hoon; Kim, MinYoung; Ryu, Ju Seok

    2014-06-01

    To characterize neuropathic pain in patients with spinal cord injury (SCI) according to classification used in the study by Baron et al. (Baron classification), a classification of neuropathic pain based on the mechanism. To also compare the patterns of neuropathic pain in SCI patients with those in patients with other etiologies and to determine the differences in patterns of neuropathic pain between the etiologies. This was a descriptive cross-sectional study. We used the Baron classification to investigate the characteristics of neuropathic pain in SCI. Sixty-one SCI patients with neuropathic pain (The Leeds assessment of neuropathic symptoms and signs score ≥12) were enrolled in this study between November 2012 and August 2013, after excluding patients patients with visual analog scale (VAS) score patients, and patients with systemic disease or pain other than neuropathic pain. The most common pain characteristic was pricking pain followed by electrical pain and numbness. The mean VAS score of at-level neuropathic pain was 7.51 and that of below-level neuropathic pain was 6.83. All of the patients suffered from rest pain, but 18 (54.6%) patients with at-level neuropathic pain and 20 (50.0%) patients with below-level neuropathic pain suffered from evoked pain. There was no significant difference in between at-level and below-level neuropathic pains. The result was quite different from the characteristics of post-herpetic neuralgia, but it was similar to the characteristics of diabetic neuropathy as shown in the study by Baron et al., which means that sensory nerve deafferentation may be the most common pathophysiologic mechanism of neuropathic pain after SCI. Since in our study, we included short and discrete symptoms and signs based on diverse mechanisms, our results could be helpful for determining further evaluation and treatment.

  1. Phenytoin Cream for the Treatment of Neuropathic Pain: Case Series

    Directory of Open Access Journals (Sweden)

    David J. Kopsky

    2018-05-01

    minutes after the test application, the mean pain reduction on the NRS in the areas where the phenytoin 10% cream and the placebo cream were applied was 3.3 (CI: 2.3 to 4.4, p < 0.01 and 1.1 (CI: 0.4 to 1.9, p < 0.05, respectively. In all 16 patients, the phenytoin plasma levels were below the limit of detection. So far, no systemic side effects were reported. Two patients only reported local side effects: a transient burning aggravation and skin rash. CONCLUSION: In this case series, the phenytoin cream had reduced neuropathic pain considerably, with a fast onset of analgesic effect.

  2. Differential pain modulation in patients with peripheral neuropathic pain and fibromyalgia.

    Science.gov (United States)

    Gormsen, Lise; Bach, Flemming W; Rosenberg, Raben; Jensen, Troels S

    2017-12-29

    Background The definition of neuropathic pain has recently been changed by the International Association for the Study of Pain. This means that conditions such as fibromyalgia cannot, as sometimes discussed, be included in the neuropathic pain conditions. However, fibromyalgia and peripheral neuropathic pain share common clinical features such as spontaneous pain and hypersensitivity to external stimuli. Therefore, it is of interest to directly compare the conditions. Material and methods In this study we directly compared the pain modulation in neuropathic pain versus fibromyalgia by recording responses to a cold pressor test in 30 patients with peripheral neuropathic pain, 28 patients with fibromyalgia, and 26 pain-free age-and gender-matched healthy controls. Patients were asked to rate their spontaneous pain on a visual analog scale (VAS (0-100 mm) immediately before and immediately after the cold pressor test. Furthermore the duration (s) of extremity immersion in cold water was used as a measure of the pain tolerance threshold, and the perceived pain intensity at pain tolerance on the VAS was recorded on the extremity in the water after the cold pressor test. In addition, thermal (thermo tester) and mechanical stimuli (pressure algometer) were used to determine sensory detection, pain detection, and pain tolerance thresholds in different body parts. All sensory tests were done by the same examiner, in the same room, and with each subject in a supine position. The sequence of examinations was the following: (1) reaction time, (2) pressure thresholds, (3) thermal thresholds, and (4) cold pressor test. Reaction time was measured to ensure that psychomotoric inhibitions did not influence pain thresholds. Results Pain modulation induced by a cold pressor test reduced spontaneous pain by 40% on average in neuropathic pain patients, but increased spontaneous pain by 2.6% in fibromyalgia patients. This difference between fibromyalgia and neuropathic pain patients was

  3. Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults.

    Science.gov (United States)

    Gibson, William; Wand, Benedict M; O'Connell, Neil E

    2017-09-14

    active treatments or favoured the comparator intervention (very low quality evidence). We were unable to report on other primary and secondary outcomes in these single trials (health-related quality of life, global impression of change and changes in analgesic use).Of the 15 included studies, three reported adverse events which were minor and limited to 'skin irritation' at or around the site of electrode placement (very low quality evidence). Three studies reported no adverse events while the remainder did not report any detail with regard adverse events. In this review, we reported on the comparison between TENS and sham TENS. The quality of the evidence was very low meaning we were unable to confidently state whether TENS is effective for pain control in people with neuropathic pain. The very low quality of evidence means we have very limited confidence in the effect estimate reported; the true effect is likely to be substantially different. We make recommendations with respect to future TENS study designs which may meaningfully reduce the uncertainty relating to the effectiveness of this treatment modality.

  4. Inflammation and neuropathic attacks in hereditary brachial plexus neuropathy

    Science.gov (United States)

    Klein, C; Dyck, P; Friedenberg, S; Burns, T; Windebank, A; Dyck, P

    2002-01-01

    Objective: To study the role of mechanical, infectious, and inflammatory factors inducing neuropathic attacks in hereditary brachial plexus neuropathy (HBPN), an autosomal dominant disorder characterised by attacks of pain and weakness, atrophy, and sensory alterations of the shoulder girdle and upper limb muscles. Methods: Four patients from separate kindreds with HBPN were evaluated. Upper extremity nerve biopsies were obtained during attacks from a person of each kindred. In situ hybridisation for common viruses in nerve tissue and genetic testing for a hereditary tendency to pressure palsies (HNPP; tomaculous neuropathy) were undertaken. Two patients treated with intravenous methyl prednisolone had serial clinical and electrophysiological examinations. One patient was followed prospectively through pregnancy and during the development of a stereotypic attack after elective caesarean delivery. Results: Upper extremity nerve biopsies in two patients showed prominent perivascular inflammatory infiltrates with vessel wall disruption. Nerve in situ hybridisation for viruses was negative. There were no tomaculous nerve changes. In two patients intravenous methyl prednisolone ameliorated symptoms (largely pain), but with tapering of steroid dose, signs and symptoms worsened. Elective caesarean delivery did not prevent a typical postpartum attack. Conclusions: Inflammation, probably immune, appears pathogenic for some if not all attacks of HBPN. Immune modulation may be useful in preventing or reducing the neuropathic attacks, although controlled trials are needed to establish efficacy, as correction of the mutant gene is still not possible. The genes involved in immune regulation may be candidates for causing HBPN disorders. PMID:12082044

  5. Presence of neuropathic pain may explain poor performances on olfactory testing in diabetes mellitus patients.

    Science.gov (United States)

    Brady, Shauna; Lalli, Paul; Midha, Nisha; Chan, Ayechen; Garven, Alexandra; Chan, Cynthia; Toth, Cory

    2013-07-01

    Olfactory dysfunction in neurodegenerative conditions such as Parkinson's syndrome and Alzheimer's disease can hallmark disease onset. We hypothesized that patients with diabetes mellitus, a condition featuring peripheral and central neurodegeneration, would have decreased olfaction abilities. We examined participants with diabetic peripheral neuropathy, participants with diabetes without diabetic peripheral neuropathy, and control participants in blinded fashion using standardized Sniffin' Sticks. Diabetic peripheral neuropathy severity was quantified using the Utah Early Neuropathy Scale. Further subcategorization of diabetic peripheral neuropathy based on presence of neuropathic pain was performed with Douleur Neuropathique 4 Questionnaires. Participants with diabetes had decreased olfactory sensitivity, impaired olfactory discrimination abilities, and reduced odor identification skills when compared with controls. However, loss of olfaction ability was, at least partially, attributed to presence of neuropathic pain on subcategory assessment, although pain severity was not associated with dysfunction. Those participants with diabetes without diabetic peripheral neuropathy and those with diabetic peripheral neuropathy without neuropathic pain had similar olfactory function as controls in general. The presence of neuropathic pain, associated with limited attention and concentration, may explain at least a portion of the olfactory dysfunction witnessed in the diabetic patient population.

  6. Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

    Science.gov (United States)

    Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

    2015-06-01

    Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

  7. Spinal cord stimulation for neuropathic pain: current perspectives

    OpenAIRE

    Wolter, Tilman

    2014-01-01

    Tilman Wolter Interdisciplinary Pain Centre, University Hospital Freiburg, Freiburg, Germany Abstract: Neuropathic pain constitutes a significant portion of chronic pain. Patients with neuropathic pain are usually more heavily burdened than patients with nociceptive pain. They suffer more often from insomnia, anxiety, and depression. Moreover, analgesic medication often has an insufficient effect on neuropathic pain. Spinal cord stimulation constitutes a therapy alternative that, to date, re...

  8. EFNS guidelines on neurostimulation therapy for neuropathic pain

    DEFF Research Database (Denmark)

    EFNS Panel on Neuropathic Pain, Vienna; Cruccu, Giorgio; Aziz, T. Z.

    2007-01-01

    Pharmacological relief of neuropathic pain is often insufficient. Electrical neurostimulation is efficacious in chronic neuropathic pain and other neurological diseases. European Federation of Neurological Societies (EFNS) launched a Task Force to evaluate the evidence for these techniques...... and to produce relevant recommendations. We searched the literature from 1968 to 2006, looking for neurostimulation in neuropathic pain conditions, and classified the trials according to the EFNS scheme of evidence for therapeutic interventions. Spinal cord stimulation (SCS) is efficacious in failed back surgery...

  9. Neuropathic pain: A personal case reflection on a critical incident

    Directory of Open Access Journals (Sweden)

    Balaji P Duraisamy

    2011-01-01

    Full Text Available Neuropathic pain is a distressing symptom for the patient and a difficult symptom for the physician to treat. There is lack of evidence-based clinical guidelines for the management of malignant neuropathic pain. The case reflection is a personal account of what has been learnt from a critical incident in a particular patient in the management of neuropathic pain. Psychological issues are known to increase pain percetion and affect the quality of life. The case reflection explores problem areas, defines lacunae in knowledge, and demonstrates active learning of the management of neuropathic pain through reflective practice.

  10. Spinal cord stimulation for neuropathic pain: current perspectives.

    Science.gov (United States)

    Wolter, Tilman

    2014-01-01

    Neuropathic pain constitutes a significant portion of chronic pain. Patients with neuropathic pain are usually more heavily burdened than patients with nociceptive pain. They suffer more often from insomnia, anxiety, and depression. Moreover, analgesic medication often has an insufficient effect on neuropathic pain. Spinal cord stimulation constitutes a therapy alternative that, to date, remains underused. In the last 10 to 15 years, it has undergone constant technical advancement. This review gives an overview of the present practice of spinal cord stimulation for chronic neuropathic pain and current developments such as high-frequency stimulation and peripheral nerve field stimulation.

  11. Neuropathic pain and cytokines: current perspectives

    Directory of Open Access Journals (Sweden)

    Clark AK

    2013-11-01

    Full Text Available Anna K Clark, Elizabeth A Old, Marzia Malcangio Wolfson Centre for Age Related Diseases, King's College London, London, UK Abstract: Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention. Keywords: anti-inflammatory cytokines, proinflammatory cytokines, microglia, astrocytes, first pain synapse

  12. Neuropathic orofacial pain: Facts and fiction.

    Science.gov (United States)

    Baad-Hansen, Lene; Benoliel, Rafael

    2017-06-01

    Definition and taxonomy This review deals with neuropathic pain of traumatic origin affecting the trigeminal nerve, i.e. painful post-traumatic trigeminal neuropathy (PTTN). Symptomatology The clinical characteristics of PTTN vary considerably, partly due to the type and extent of injury. Symptoms involve combinations of spontaneous and evoked pain and of positive and negative somatosensory signs. These patients are at risk of going through unnecessary dental/surgical procedures in the attempt to eradicate the cause of the pain, due to the fact that most dentists only rarely encounter PTTN. Epidemiology Overall, approximately 3% of patients with trigeminal nerve injuries develop PTTN. Patients are most often female above the age of 45 years, and both physical and psychological comorbidities are common. Pathophysiology PTTN shares many pathophysiological mechanisms with other peripheral neuropathic pain conditions. Diagnostic considerations PTTN may be confused with one of the regional neuralgias or other orofacial pain conditions. For intraoral PTTN, early stages are often misdiagnosed as odontogenic pain. Pain management Management of PTTN generally follows recommendations for peripheral neuropathic pain. Expert opinion International consensus on classification and taxonomy is urgently needed in order to advance the field related to this condition.

  13. Analysis of risk factors for neuropathic foot ulceration in diabetes mellitus.

    Science.gov (United States)

    Bennett, P J; Stocks, A E; Whittam, D J

    1996-03-01

    Diabetes mellitus affects about one in 25 Australians. Neuropathic foot ulceration is a frequent complication in persons with diabetes. This study evaluates the importance of different risk factors for the development of this condition. The role of nonenzymatic glycosylation and pressure beneath the sole of the foot in the pathogenesis of neuropathic foot ulcers was investigated. Twenty-seven subjects with diabetes with a recent history of neuropathic foot ulceration were matched by age and sex with a group of 50 control subjects without neuropathy or history of foot ulceration. The degree of nonenzymatic glycosylation was assessed by analyzing the average level of glycosylated hemoglobin in the 3 years prior to the development of the foot ulcer and a goniometer assessment of peripheral joint (hand and ankle) flexibility. Dynamic pressure of the plantar aspect of the foot was recorded using a Musgrave Footprint System pedobarograph during a normal gait cycle. There was no significant difference in age, sex, body mass index, and duration or type of diabetes between the ulcer and control groups. The pressure of the plantar aspect of the foot was significantly elevated (p < 0.01). Ankle joint flexibility was reduced (p < 0.01) in cases with neuropathic foot ulceration compared with the control group. There was a trend toward elevation of glycosylated hemoglobin (HbA1c fraction) or HbA1c in the ulcer group (p = 0.06). The results suggested that nonenzymatic glycosylation occurs at a more significant level in patients with diabetes with a history of neuropathic foot ulceration.

  14. 5-HT6 receptor antagonist attenuates the memory deficits associated with neuropathic pain and improves the efficacy of gabapentinoids.

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    Jayarajan, Pradeep; Nirogi, Ramakrishna; Shinde, Anil; Goura, Venkatesh; Babu, Vuyyuru Arun; Yathavakilla, Sumanth; Bhyrapuneni, Gopinadh

    2015-10-01

    Memory deficit is a co-morbid disorder in patients suffering from neuropathic pain. Gabapentin and pregabalin (gabapentinoids) are among the widely prescribed medications for the treatment of neuropathic pain. Memory loss and sedation are the commonly reported side effects with gabapentinoids. Improving the cognitive functions and attenuating drug-induced side effects may play a crucial role in the management of pain. We evaluated the effects of 5-HT6 receptor antagonists on the memory deficits associated with neuropathy. We also studied the effects of 5-HT6 receptor antagonists on the side effects, and the analgesic effects of gabapentinoids. 5-HT6 receptor antagonists attenuated the cognitive deficits in neuropathic rats. Neuropathic rats co-treated with 5-HT6 receptor antagonist and gabapentinoids showed improvement in memory. 5-HT6 receptor antagonists enhanced the analgesic effects of gabapentinoids but had no effect on the motor side effects. The observed effects may not be due to pharmacokinetic interactions. 5-HT6 receptor antagonist attenuate the cognitive deficits associated with neuropathy, and this effect is also seen when co-treated with gabapentinoids. Since, 5-HT6 antagonists improved the effectiveness of gabapentinoids, reduction in the dosage and frequency of gabapentinoids treatment may reduce the side effects. Combining 5-HT6 receptor antagonist with gabapentinoids may offer a novel treatment strategy for neuropathic pain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Cannabis-based medicines for chronic neuropathic pain in adults.

    Science.gov (United States)

    Mücke, Martin; Phillips, Tudor; Radbruch, Lukas; Petzke, Frank; Häuser, Winfried

    2018-03-07

    This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For

  16. Duloxetine in the management of diabetic peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Boomershine CS

    2011-07-01

    Full Text Available Michelle J Ormseth, Beth A Sholz, Chad S BoomershineDivision of Rheumatology and Immunology, Vanderbilt University, Nashville, TN, USAAbstract: Diabetic neuropathy affects up to 70% of diabetics, and diabetic peripheral neuropathic pain (DPNP is the most common and debilitating of the diabetic neuropathies. DPNP significantly reduces quality of life and increases management costs in affected patients. Despite the impact of DPNP, management is poor with one-quarter of patients receiving no treatment and many treated with medications having little or no efficacy in managing DPNP. Duloxetine is one of two drugs approved by the United States Food and Drug Administration for DPNP management. Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI proven safe, effective, and cost-saving in reducing DPNP symptoms at a dose of 60 mg/day. Duloxetine doses greater than 60 mg/day for DPNP management are not recommended since they are no more efficacious and associated with more side effects; addition of pregabalin or gabapentin for these patients may be beneficial. Side effects of duloxetine are generally mild and typical for the SNRI class including nausea, dizziness, somnolence, fatigue, sweating, dry mouth, constipation, and diarrhea. Given its other indications, duloxetine is a particularly good choice for DPNP treatment in patients with coexisting depression, anxiety, fibromyalgia, or chronic musculoskeletal pain. Duloxetine treatment had no clinically significant effect on glycemic control and did not increase the risk of cardiovascular events in diabetes patients. However, duloxetine use should be avoided in patients with hepatic disease or severe renal impairment. Given its safety, efficacy, and tolerability, duloxetine is an excellent choice for DPNP treatment in many patients.Keywords: duloxetine, diabetic peripheral neuropathic pain, review, treatment

  17. NMDA receptor antagonists for the treatment of neuropathic pain

    NARCIS (Netherlands)

    Collins, S.; Sigtermans, M.J.; Dahan, A.; Zuurmond, W.W.A.; Perez, R.S.G.M.

    2010-01-01

    Objective. The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis evaluating the effects of (individual) NMDA receptor antagonists on neuropathic pain, and the response

  18. Tramadol for neuropathic pain in adults.

    Science.gov (United States)

    Duehmke, Rudolf Martin; Derry, Sheena; Wiffen, Philip J; Bell, Rae F; Aldington, Dominic; Moore, R Andrew

    2017-06-15

    This review is an update of a review of tramadol for neuropathic pain, published in 2006; updating was to bring the review in line with current standards. Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Peripheral neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the peripheral nervous system. To assess the analgesic efficacy of tramadol compared with placebo or other active interventions for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials. We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from inception to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trial registries. We included randomised, double-blind trials of two weeks' duration or longer, comparing tramadol (any route of administration) with placebo or another active treatment for neuropathic pain, with subjective pain assessment by the participant. Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH), using standard methods. We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables. We identified six randomised, double-blind studies involving 438 participants

  19. Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial.

    Science.gov (United States)

    Rigo, Flavia Karine; Trevisan, Gabriela; Godoy, Maria C; Rossato, Mateus Fortes; Dalmolin, Gerusa D; Silva, Mariane A; Menezes, Mirian S; Caumo, Wolnei; Ferreira, Juliano

    2017-03-01

    Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain. Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain. We conducted a randomized, double blind, active-controlled parallel-group clinical trial. Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period. During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia. Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms. This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain.Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid.

  20. Neuropathic sensory symptoms: association with pain and psychological factors

    Directory of Open Access Journals (Sweden)

    Shaygan M

    2014-05-01

    Full Text Available Maryam Shaygan,1 Andreas Böger,2 Birgit Kröner-Herwig11Department of Clinical Psychology and Psychotherapy, University of Göttingen, Germany; 2Pain Management Clinic at the Red Cross Hospital, Kassel, GermanyBackground: A large number of population-based studies of chronic pain have considered neuropathic sensory symptoms to be associated with a high level of pain intensity and negative affectivity. The present study examines the question of whether this association previously found in non-selected samples of chronic pain patients can also be found in chronic pain patients with underlying pathology of neuropathic sensory symptoms.Methods: Neuropathic sensory symptoms in 306 patients with chronic pain diagnosed as typical neuropathic pain, radiculopathy, fibromyalgia, or nociceptive back pain were assessed using the Pain DETECT Questionnaire. Two separate cluster analyses were performed to identify subgroups of patients with different levels of self-reported neuropathic sensory symptoms and, furthermore, to identify subgroups of patients with distinct patterns of neuropathic sensory symptoms (adjusted for individual response bias regarding specific symptoms.Results: ANOVA (analysis of variance results in typical neuropathic pain, radiculopathy, and fibromyalgia showed no significant differences between the three levels of neuropathic sensory symptoms regarding pain intensity, pain chronicity, pain catastrophizing, pain acceptance, and depressive symptoms. However, in nociceptive back pain patients, significant differences were found for all variables except pain chronicity. When controlling for the response bias of patients in ratings of symptoms, none of the patterns of neuropathic sensory symptoms were associated with pain and psychological factors.Conclusion: Neuropathic sensory symptoms are not closely associated with higher levels of pain intensity and cognitive-emotional evaluations in chronic pain patients with underlying pathology of

  1. Spinal cord stimulation for neuropathic pain: current perspectives

    Directory of Open Access Journals (Sweden)

    Wolter T

    2014-11-01

    Full Text Available Tilman Wolter Interdisciplinary Pain Centre, University Hospital Freiburg, Freiburg, Germany Abstract: Neuropathic pain constitutes a significant portion of chronic pain. Patients with neuropathic pain are usually more heavily burdened than patients with nociceptive pain. They suffer more often from insomnia, anxiety, and depression. Moreover, analgesic medication often has an insufficient effect on neuropathic pain. Spinal cord stimulation constitutes a therapy alternative that, to date, remains underused. In the last 10 to 15 years, it has undergone constant technical advancement. This review gives an overview of the present practice of spinal cord stimulation for chronic neuropathic pain and current developments such as high-frequency stimulation and peripheral nerve field stimulation. Keywords: spinal cord stimulation, neuropathic pain, neurostimulation

  2. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation.

    Science.gov (United States)

    Simpson, E L; Duenas, A; Holmes, M W; Papaioannou, D; Chilcott, J

    2009-03-01

    This report addressed the question 'What is the clinical and cost-effectiveness of spinal cord stimulation (SCS) in the management of chronic neuropathic or ischaemic pain?' Thirteen electronic databases [including MEDLINE (1950-2007), EMBASE (1980-2007) and the Cochrane Library (1991-2007)] were searched from inception; relevant journals were hand-searched; and appropriate websites for specific conditions causing chronic neuropathic/ischaemic pain were browsed. Literature searches were conducted from August 2007 to September 2007. A systematic review of the literature sought clinical and cost-effectiveness data for SCS in adults with chronic neuropathic or ischaemic pain with inadequate response to medical or surgical treatment other than SCS. Economic analyses were performed to model the cost-effectiveness and cost-utility of SCS in patients with neuropathic or ischaemic pain. From approximately 6000 citations identified, 11 randomised controlled trials (RCTs) were included in the clinical effectiveness review: three of neuropathic pain and eight of ischaemic pain. Trials were available for the neuropathic conditions failed back surgery syndrome (FBSS) and complex regional pain syndrome (CRPS) type I, and they suggested that SCS was more effective than conventional medical management (CMM) or reoperation in reducing pain. The ischaemic pain trials had small sample sizes, meaning that most may not have been adequately powered to detect clinically meaningful differences. Trial evidence failed to demonstrate that pain relief in critical limb ischaemia (CLI) was better for SCS than for CMM; however, it suggested that SCS was effective in delaying refractory angina pain onset during exercise at short-term follow-up, although not more so than coronary artery bypass grafting (CABG) for those patients eligible for that surgery. The results for the neuropathic pain model suggested that the cost-effectiveness estimates for SCS in patients with FBSS who had inadequate

  3. Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats.

    Science.gov (United States)

    Yoon, Jeong-Ho; Son, Jo-Young; Kim, Min-Ji; Kang, Song-Hee; Ju, Jin-Sook; Bae, Yong-Chul; Ahn, Dong-Kuk

    2018-05-01

    The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.

  4. Overexpression of GDNF in the uninjured DRG exerts analgesic effects on neuropathic pain following segmental spinal nerve ligation in mice.

    Science.gov (United States)

    Takasu, Kumiko; Sakai, Atsushi; Hanawa, Hideki; Shimada, Takashi; Suzuki, Hidenori

    2011-11-01

    Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein (EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia in association with an increase in GDNF protein expression in each virus injection site, whereas injection into the injured L5 DRG or plantar skin had no effects. These results suggest that GDNF exerts its analgesic effects in the neuropathic pain state by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by the uninjured DRG neurons. This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by these neurons. Therefore, research focusing on these GDNF-dependent neurons in the uninjured DRG would provide a new strategy for treating neuropathic pain. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Event-related cortical processing in neuropathic pain under long-term spinal cord stimulation.

    Science.gov (United States)

    Weigel, Ralf; Capelle, H Holger; Flor, Herta; Krauss, Joachim K

    2015-01-01

    Several mechanisms were suggested in the past to explain the beneficial effect of spinal cord stimulation (SCS) in patients suffering from neuropathic pain. Little is known about potential supraspinal mechanisms. In this study cortical signaling of patients with neuropathic pain and successful long-term treatment with SCS was analyzed. Observational study. University hospital, neurosurgical department, outpatient clinic for movement disorders and pain, institute for cognitive and clinical neuroscience. Nine patients with neuropathic pain of a lower extremity with a lasting response to chronic SCS were included. Cortical activity was analyzed using event-related potentials of the electroencephalogram after non-painful and painful stimulation. Each patient was tested under the effect of long-term SCS and 24 hours after cessation of SCS. Cortical areas involved in the peaks of evoked potentials were localized using a source localization method based on a fixed dipole model. Detection threshold and intensity of non-painful stimulation did not differ significantly on both sides. Pain threshold was significantly lower on the neuropathic side under the effect of SCS (P = 0.03). Bilateral pain thresholds were significantly lower (P = 0.03 healthy side, P = 0.003 neuropathic side) in 5 patients with increased pain after cessation of SCS. Under the effect of SCS cortical negativities (N1, N2, N3) and positivities (P1) demonstrated bilaterally comparable amplitudes. After cessation of SCS, decreased threshold for peripheral stimulation resulted in lowered negativities on both sides. The positivity P1 was differentially regulated and was reduced more contralateral to the unaffected side. N2 was localized at the sensory representation of the leg within the homunculus. The main vector of P1 was localized within the cingular cortex (CC) and moved more anteriorly under the effect of SCS. The exact time span that SCS continues to have an effect is not known. However, due to patient

  6. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Science.gov (United States)

    Caspani, Ombretta; Zurborg, Sandra; Labuz, Dominika; Heppenstall, Paul A

    2009-10-08

    Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG) and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI) model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI) of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  7. Neural tissue engineering scaffold with sustained RAPA release relieves neuropathic pain in rats.

    Science.gov (United States)

    Ding, Tan; Zhu, Chao; Kou, Zhen-Zhen; Yin, Jun-Bin; Zhang, Ting; Lu, Ya-Cheng; Wang, Li-Ying; Luo, Zhuo-Jing; Li, Yun-Qing

    2014-09-01

    To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1.3 (Nav1.3), 1.7 (Nav1.7), and 1.8 (Nav1.8) through immunohistochemistry (IHC) and Western Blot, along with the observation of postsurgical pathological pain in rats by pain-related behavior approaches. Relatively small upregulation of DRG sodium channels was observed in the experimental group (RAPA+poly(lactic-co-glycolic acid) (PLGA)+stent) after surgery, along with low degrees of neuropathic pain and anxiety, which were similar to those in the Autologous nerve graft group. Autoimmune inflammatory response plays a leading role in the occurrence of post-traumatic neuropathic pain, and that RAPA significantly inhibits the abnormal upregulation of sodium channels to reduce pain by alleviating inflammatory response. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

    Science.gov (United States)

    Kamimura, Rantaro; Hossain, Mohammad Z; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Takahashi, Kojiro; Otake, Masanori; Saito, Isao; Kitagawa, Junichi

    2018-03-24

    Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

  9. The effects of music therapy on pain in patients with neuropathic pain.

    Science.gov (United States)

    Korhan, Esra Akın; Uyar, Meltem; Eyigör, Can; Hakverdioğlu Yönt, Gülendam; Çelik, Serkan; Khorshıd, Leyla

    2014-03-01

    The aim of this study was to investigate the effect of relaxing music on pain intensity in patients with neuropathic pain. A quasi-experimental study, repeated measures design was used. Thirty patients, aged 18-70 years, with neuropathic pain and hospitalized in an Algology clinic were identified as a convenience sample. Participants received 60 minutes of music therapy. Classical Turkish music was played to patients using a media player (MP3) and headphones. Participants had pain scores taken immediately before the intervention and at the 30th and 60th minutes of the intervention. Data were collected over a 6-month period in 2012. The patients' mean pain intensity scores were reduced by music, and that decrease was progressive over the 30th and 60th minutes of the intervention, indicating a cumulative dose effect. The results of this study implied that the inclusion of music therapy in the routine care of patients with neuropathic pain could provide nurses with an effective practice for reducing patients' pain intensity. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  10. Neuropathic pain: is quantitative sensory testing helpful?

    Science.gov (United States)

    Krumova, Elena K; Geber, Christian; Westermann, Andrea; Maier, Christoph

    2012-08-01

    Neuropathic pain arises as a consequence of a lesion or disease affecting the somatosensory system and is characterised by a combination of positive and negative sensory symptoms. Quantitative sensory testing (QST) examines the sensory perception after application of different mechanical and thermal stimuli of controlled intensity and the function of both large (A-beta) and small (A-delta and C) nerve fibres, including the corresponding central pathways. QST can be used to determine detection, pain thresholds and stimulus-response curves and can thus detect both negative and positive sensory signs, the second ones not being assessed by other methods. Similarly to all other psychophysical tests QST requires standardised examination, instructions and data evaluation to receive valid and reliable results. Since normative data are available, QST can contribute also to the individual diagnosis of neuropathy, especially in the case of isolated small-fibre neuropathy, in contrast to the conventional electrophysiology which assesses only large myelinated fibres. For example, detection of early stages of subclinical neuropathy in symptomatic or asymptomatic patients with diabetes mellitus can be helpful to optimise treatment and identify diabetic foot at risk of ulceration. QST assessed the individual's sensory profile and thus can be valuable to evaluate the underlying pain mechanisms which occur in different frequencies even in the same neuropathic pain syndromes. Furthermore, assessing the exact sensory phenotype by QST might be useful in the future to identify responders to certain treatments in accordance to the underlying pain mechanisms.

  11. Pharmacological treatment of diabetic neuropathic pain.

    Science.gov (United States)

    Smith, Howard S; Argoff, Charles E

    2011-03-26

    Neuropathic pain continues to be a difficult and challenging clinical issue to deal with effectively. Painful diabetic polyneuropathy is a complex pain condition that occurs with reasonable frequency in the population and it may be extremely difficult for clinicians to provide patients with effective analgesia. Chronic neuropathic pain may occur in approximately one of every four diabetic patients. The pain may be described as burning or a deep-seated ache with sporadic paroxysms of lancinating painful exacerbations. The pain is often constant, moderate to severe in intensity, usually primarily involves the feet and generally tends to worsen at night. Treatment may be multimodal but largely involves pharmacological approaches. Pharmacological therapeutic options include antidepressants (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors), α2δ ligands and topical (5%) lidocaine patch. Other agents may be different antiepileptic drugs (carbamazepine, lamotrigine, topiramate), topical capsaicin, tramadol and other opioids. Progress continues with respect to understanding various mechanisms that may contribute to painful diabetic neuropathy. Agents that may hold some promise include neurotrophic factors, growth factors, immunomodulators, gene therapy and poly (adenosine diphosphate-ribose) polymerase inhibitors. It is hoped that in the future clinicians will be able to assess patient pathophysiology, which may help them to match optimal therapeutic agents to target individual patient aberrant mechanisms.

  12. An Algorithm for Neuropathic Pain Management in Older People.

    Science.gov (United States)

    Pickering, Gisèle; Marcoux, Margaux; Chapiro, Sylvie; David, Laurence; Rat, Patrice; Michel, Micheline; Bertrand, Isabelle; Voute, Marion; Wary, Bernard

    2016-08-01

    Neuropathic pain frequently affects older people, who generally also have several comorbidities. Elderly patients are often poly-medicated, which increases the risk of drug-drug interactions. These patients, especially those with cognitive problems, may also have restricted communication skills, making pain evaluation difficult and pain treatment challenging. Clinicians and other healthcare providers need a decisional algorithm to optimize the recognition and management of neuropathic pain. We present a decisional algorithm developed by a multidisciplinary group of experts, which focuses on pain assessment and therapeutic options for the management of neuropathic pain, particularly in the elderly. The algorithm involves four main steps: (1) detection, (2) evaluation, (3) treatment, and (4) re-evaluation. The detection of neuropathic pain is an essential step in ensuring successful management. The extent of the impact of the neuropathic pain is then assessed, generally with self-report scales, except in patients with communication difficulties who can be assessed using behavioral scales. The management of neuropathic pain frequently requires combination treatments, and recommended treatments should be prescribed with caution in these elderly patients, taking into consideration their comorbidities and potential drug-drug interactions and adverse events. This algorithm can be used in the management of neuropathic pain in the elderly to ensure timely and adequate treatment by a multidisciplinary team.

  13. Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Taraneh Moini Zanjani

    2013-05-01

    Full Text Available Please cite this article as: Moini Zanjani T, Saghaei E, Ameli H, Sabetkasaei M. Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain. Novel Biomed 2013;1:16-22.Background: Neuropathic pain is a chronic pain due to a disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Here we compared the analgesic effect of nefopam, and morphine in chronic constriction injury (CCI model of neuropathic pain.Methods: Male wistar rat (150-200g, n=8 were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. In CCI model of neuropathic pain, the left sciatic nerve was exposed and 4 loose chromic gut ligatures were placed around the nerve proximal to the trifurcation. Ketamine 60mg/kg and xylazine 10 mg/kg were used for anesthesia. Nefopam (10, 20, 30mg/kg, and morphine (1, 3, 5mg/kg were injected 30 minutes before surgery and continued daily to day 14 post-ligation. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were respectively used as pain behavioral tests. Experiments were performed on day 0 (before surgery and days 1, 3, 5,7,10 and 14 post injury. Behavioral studies were performed in a quiet room between 9:00 to 11:00 AM. All experiments followed the IASP guidelines on ethical standards for investigation of experimental pain in animals.Results: Nefopam (20 and 30mg/kg blocked mechanical and cold allodynia during the experimental period, but the analgesic effects of morphine (5mg/kg lasted for 7 days.Conclusions: It seems that nefopam could effectively reduce pain behavior compared to morphine with reduced adverse effects.

  14. Can We Distinguish between Inflammatory and Neuropathic Pain?

    Directory of Open Access Journals (Sweden)

    Gary J Bennett

    2006-01-01

    Full Text Available Inflammatory and neuropathic pain were once considered to be distinct entities. However, research over the past decade or so has brought to light many shared mechanisms, and the distinction between the two is no longer clear. Consideration of mechanisms, symptoms and the effects of analgesic drugs does not reveal any definitive or universally applicable differentiating factors. Given the present level of understanding, it may not be possible to distinguish between inflammatory and neuropathic pain in a large number of patients, and a satisfying definition of neuropathic pain may not be possible.

  15. A preliminary report on stem cell therapy for neuropathic pain in humans

    Directory of Open Access Journals (Sweden)

    Vickers ER

    2014-05-01

    Full Text Available E Russell Vickers,1 Elisabeth Karsten,2 John Flood,3 Richard Lilischkis21Sydney Oral and Maxillofacial Surgery, NSW, Australia; 2Regeneus Ltd, Gordon, NSW, Australia; 3St Vincents Hospital, Sydney, NSW, AustraliaObjective: Mesenchymal stem cells (MSCs have been shown in animal models to attenuate chronic neuropathic pain. This preliminary study investigated if: i injections of autologous MSCs can reduce human neuropathic pain and ii evaluate the safety of the procedure.Methods: Ten subjects with symptoms of neuropathic trigeminal pain underwent liposuction. The lipoaspirate was digested with collagenase and washed with saline three times. Following centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i pain intensity measured by standard numerical rating scale from 0–10 and ii daily dosage requirements of antineuropathic pain medication.Results: Subjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range 27–80 years with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the stem cell therapy (n=41 oral and facial injection sites. Clinical pain outcomes showed that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58 and at 6 months had decreased to 4.3 (SD 3.28, P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed 5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student's t-test.Conclusion: This preliminary open-labeled study showed autologous administration of stem cells for neuropathic trigeminal pain

  16. Coregulation of endoplasmic reticulum stress and oxidative stress in neuropathic pain and disinhibition of the spinal nociceptive circuitry.

    Science.gov (United States)

    Ge, Yanhu; Jiao, Yingfu; Li, Peiying; Xiang, Zhenghua; Li, Zhi; Wang, Long; Li, Wenqian; Gao, Hao; Shao, Jiayun; Wen, Daxiang; Yu, Weifeng

    2018-05-01

    The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress. Other important findings in this study including the following: (1) nociceptive behavior was alleviated in SNL rat as long as tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2) inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3) blocking protein disulfide isomerase pharmacologically reduced ER stress and nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER stress were mainly neurons; and (5) whole-cell recordings made in slide preparations revealed significant inhibition of GABA-ergic interneuron activity in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together, results of the current study demonstrate that coregulation of ER stress and oxidative stress played an important role in neuropathic pain process. Inhibiting SDH ER stress could be a potential novel strategy to manage neuropathic pain.

  17. Peripheral nerve field stimulation for chronic neuropathic pain: a single institution experience.

    Science.gov (United States)

    D'Ammando, A; Messina, G; Franzini, A; Dones, I

    2016-04-01

    Peripheral nerve field stimulation (PNFS) is a novel neurosurgical procedure consisting of implantation of subcutaneous leads in specific painful areas in different types of painful, drug-resistant syndromes. The objective of this study was to evaluate the efficacy of PNFS in several patients affected by different chronic neuropathic pain syndromes, along with its risks, limits and possible correlation between the results achieved and the patients' main symptoms. Twenty-two patients affected by different types of chronic neuropathic pain were submitted to PNFS at the Department of Neurosurgery of the Istituto Neurologico "C. Besta" in Milan between July 2009 and July 2013. The visual analog scale (VAS) and variations in the use of analgesic drugs, along with complications, were considered to assess results. In 59 % of our patients, an average pain reduction of 5.50 points on the visual analog scale was observed (average pre-implant score 8.86 and average post-implant score 3.36). These patients reduced their analgesic drug use after PNFS. We observed no early or long-term complications after our last follow-up evaluation. PNFS can be considered an effective and safe option to treat carefully selected, drug-resistant and chronic neuropathic pain patients; the reversibility of the procedure and its lack, at least in our hands, of long-term complications may contribute to wider use of this procedure.

  18. Cervical Spinal Cord and Dorsal Nerve Root Stimulation for Neuropathic Upper Limb Pain.

    Science.gov (United States)

    Levine, Adrian B; Parrent, Andrew G; MacDougall, Keith W

    2017-01-01

    Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain in the lower limbs. Upper limb pain comprises a significant proportion of neuropathic pain patients, but is often difficult to target specifically and consistently with paresthesias. We hypothesized that the use of dorsal nerve root stimulation (DNRS), as an option along with SCS, would help us better relieve pain in these patients. All 35 patients trialed with spinal stimulation for upper limb pain between July 1, 2011, and October 31, 2013, were included. We performed permanent implantation in 23/35 patients based on a visual analogue scale pain score decrease of ≥50% during trial stimulation. Both the SCS and DNRS groups had significant improvements in average visual analogue scale pain scores at 12 months compared with baseline, and the majority of patients in both groups obtained ≥50% pain relief. The majority of patients in both groups were able to reduce their opioid use, and on average had improvements in Short Form-36 quality of life scores. Complication rates did not differ significantly between the two groups. Treatment with SCS or DNRS provides meaningful long-term relief of chronic neuropathic pain in the upper limbs.

  19. Ketamine for acute neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Kim, Kyongsong; Mishina, Masahiro; Kokubo, Rinko; Nakajima, Takao; Morimoto, Daijiro; Isu, Toyohiko; Kobayashi, Shiro; Teramoto, Akira

    2013-06-01

    Ketamine, an N-methyl-d-aspartic acid (NMDA) receptor antagonist, may be useful for treating neuropathic pain, which is often difficult to control. We report a prospective study of 13 patients with acute neuropathic pain due to spinal cord injury (SCI) treated with ketamine. All underwent a test challenge with 5mg ketamine. Patients with satisfactory responses were then treated intravenously and subsequently perorally with ketamine. Pre- and post-treatment pain was recorded on a visual analogue scale. All 13 patients responded positively to the ketamine test challenge and underwent continued ketamine administration. At the cessation of treatment and alter at final follow up, pain was decreased by 74.7% and 96.8%, respectively. The average administration period was 17.2 days; it was longer (59 days) in one patient treated in the subacute phase. All patients suffered allodynia-type pain and experienced 30% or less of their original pain intensity upon test challenge. Side effects were noted in five patients, although their severity did not require treatment cessation. In patients with SCI, ketamine reduced allodynia. Particularly good results were obtained in patients treated in the acute phase and these patients did not experience post-treatment symptom recurrence. Our results suggest that in patients with SCI, ketamine is useful for treating neuropathic pain in the acute phase. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis.

    Science.gov (United States)

    Russo, Margherita; Naro, Antonino; Leo, Antonino; Sessa, Edoardo; D'Aleo, Giangaetano; Bramanti, Placido; Calabrò, Rocco Salvatore

    2016-06-01

    The aim of our study was to better investigate the role of Sativex(®) in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment. Pain is a common symptom of MS, affecting up to 70% of patients. Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results. Clinical pain assessment in MS is very difficult, and more objective tools are necessary to better quantify this symptom and its potential response to the treatments. We enrolled 20 MS patients (10 with and 10 without neuropathic pain), who underwent a specific clinical (such as visual analog scale) and neurophysiological assessment (by means of laser-evoked potentials and transcranial magnetic stimulation), before and after 4 weeks of Sativex administration. One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life. Interestingly, such effects were paralleled by an increase of fronto-central γ-band oscillation and of pain-motor integration strength. Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity.

    Science.gov (United States)

    Thibault, Karine; Rivière, Sébastien; Lenkei, Zsolt; Férézou, Isabelle; Pezet, Sophie

    2016-01-01

    Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components. Our results show that chronic neuropathic orofacial pain is associated with decreased haemodynamic responsiveness to whisker stimulation in the barrel field cortex. This reduced functional activation is likely due to the increased basal neuronal activity (measured indirectly using cFos and phospho-ERK immunoreactivity) observed in several cortical areas, including the contralateral barrel field, motor and cingulate cortices. In the same animals, immunohistochemical analysis of markers for active pre- or postsynaptic elements (Piccolo and phospho-Cofilin, respectively) revealed an increased immunofluorescence in deep cortical layers of the contralateral barrel field, motor and cingulate cortices. These results suggest that long-lasting orofacial neuropathic pain is associated with exacerbated neuronal activity and synaptic plasticity at the cortical level.

  2. Antidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta-Analysis.

    Science.gov (United States)

    Mehta, Swati; Guy, Stacey; Lam, Tracey; Teasell, Robert; Loh, Eldon

    2015-01-01

    To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI). A systematic search was conducted using multiple databases for relevant articles published from 1980 to April 2014. Randomized controlled trials (RCTs) involving antidepressant treatment of neuropathic pain with ≥ 3 individuals and ≥ 50% of study population with SCI were included. Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen's d to calculate standardized mean difference, standard error, and 95% confidence interval for primary (pain) and other secondary outcomes was conducted. Four RCTs met inclusion criteria. Of these, 2 studies assessed amitriptyline, 1 trazadone, and 1 duloxetine among individuals with neuropathic SCI pain. A small effect was seen in the effectiveness of antidepressants in decreasing pain among individuals with SCI (standardized mean difference = 0.34 ± 0.15; 95% CI, 0.05-0.62; P = .02). A number needed to treat of 3.4 for 30% or more pain relief was found by pooling 2 studies. Of these, significantly higher risk of experiencing constipation (risk ratio [RR] = 1.74; 95% CI, 1.09-2.78; P = .02) and dry mouth (RR = 1.39; 95% CI, 1.04-1.85; P = .02) was found amongst individuals receiving antidepressant treatment compared to those in the control group. The current meta-analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required.

  3. Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2018-01-01

    Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.

  4. Effect the exercise program on neuropathic pain intensity in patients with paraplegia Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Sedghi Goyaghaj N

    2015-11-01

    Full Text Available Background and Objective: Patients with spinal cord injury suffer from continuous and persistent neuropathic pain that has a destructive impact on their quality of life. Exercise therapy is one of the non-pharmacological interventions that is recommended to control chronic pain, This study aimed to determine the effect of exercise program on neuropathic pain intensity in patients with paraplegia Spinal Cord Injury. Materials and Method: This study is a clinical trial.that population was the all of the patients with spinal cord injury, who referred to one of the educational hospitals in Tehran in 2014, 40 patient were selected based on purposive sampling and were randomly allocated into two groups of experimental and control. Exercise program for paraplegia spinal cord injury was implemented in experimental group during twelve 45-60minutes sessions, twice a week. Data collection was done before and one week after the intervention through using personal information form and, The International Spinal Cord Injury Pain Basic Data Set. Data were analyzed with statistical software SPSS19 and Fisher's exact test, Independent samples T-test Paired T-test and Chi square. Results: The mean score of neuropathic pain intensity before the intervention was 8.05 ± 1.51 in intervention group and 7.57 ± 1.21 in the control group. These amounts after the intervention were 5.55 ± 1.61 and 7.37 ± 1.05 respectively (p < 0.001. Conclusion: Results showed that the regular exercise program can reduce neuropathic pain severity in patients with spinal cord injuries and it can be recommended as a non-pharmacological method of pain control in these patients.

  5. Minocycline Does Not Decrease Intensity of Neuropathic Pain Intensity, But Does Improve Its Affective Dimension.

    Science.gov (United States)

    Sumitani, Masahiko; Ueda, Hiroshi; Hozumi, Jun; Inoue, Reo; Kogure, Takamichi; Yamada, Yoshitsugu; Kogure, Takamichi

    2016-01-01

    Recent understanding of the neuron-glia communication shed light on an important role of microglia to develop neuropathic pain The analgesic effect of minocycline on neuropathic pain is promising but it remains unclear in clinical settings. This study included 20 patients with neuropathic pain of varied etiologies. We administered 100 mg/day of minocycline for 1 week and then 200 mg/day for 3 weeks, as an open-label adjunct to conventional analgesics. An 11-point numerical rating scale. (NRS) and the short-form McGill Pain Questionnaire (SF-MPQ) were used to evaluate pain severity. The data were collected at baseline and after 4 weeks of therapy and analyzed using the Wilcoxon signed-rank test. All except two of the patients tolerated the full dose of minocycline. There was no significant improvement in the scoring of NRS (5.6 ± 1.2 at baseline vs. 5.3 ± 1.9 at 4 weeks; P =.60). The total score of the SF-MPQ decreased significantly (17.2 ± 7.4 vs. 13.9 ± 9.6; P =.02), particularly in the affective subscale (4.4 ± 2.7 vs. 3.3 ± 3.6; P =.007) but not so in the sensory subscale (12.8 ± 5.2 vs. 10.6 ± 6.2; P =.06). We conclude that minocycline failed to decrease pain intensity but succeeded in reducing the affective dimension associated with neuropathic pain.

  6. Orofacial neuropathic pain induced by oxaliplatin: downregulation of KCNQ2 channels in V2 trigeminal ganglion neurons and treatment by the KCNQ2 channel potentiator retigabine.

    Science.gov (United States)

    Ling, Jennifer; Erol, Ferhat; Viatchenko-Karpinski, Viacheslav; Kanda, Hirosato; Gu, Jianguo G

    2017-01-01

    Neuropathic pain induced by chemotherapy drugs such as oxaliplatin is a dose-limiting side effect in cancer treatment. The mechanisms underlying chemotherapy-induced neuropathic pain are not fully understood. KCNQ2 channels are low-threshold voltage-gated K+ channels that play a role in controlling neuronal excitability. Downregulation of KCNQ2 channels has been proposed to be an underlying mechanism of sensory hypersensitivity that leads to neuropathic pain. However, it is currently unknown whether KCNQ channels may be downregulated by chemotherapy drugs in trigeminal ganglion neurons to contribute to the pathogenesis of chemotherapy-induced orofacial neuropathic pain. In the present study, mechanical sensitivity in orofacial regions is measured using the operant behavioral test in rats treated with oxaliplatin. Operant behaviors in these animals show the gradual development of orofacial neuropathic pain that manifests with orofacial mechanical allodynia. Immunostaining shows strong KCNQ2 immunoreactivity in small-sized V2 trigeminal ganglion neurons in controls, and the numbers of KCNQ2 immunoreactivity positive V2 trigeminal ganglion neurons are significantly reduced in oxaliplatin-treated animals. Immunostaining is also performed in brainstem and shows strong KCNQ2 immunoreactivity at the trigeminal afferent central terminals innervating the caudal spinal trigeminal nucleus (Vc) in controls, but the KCNQ2 immunoreactivity intensity is significantly reduced in oxaliplatin-treated animals. We further show with the operant behavioral test that oxaliplatin-induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine. Taken together, these findings suggest that KCNQ2 downregulation may be a cause of oxaliplatin-induced orofacial neuropathic pain and KCNQ2 potentiators may be useful for alleviating the neuropathic pain.

  7. EFNS guidelines on neurostimulation therapy for neuropathic pain

    DEFF Research Database (Denmark)

    EFNS Panel on Neuropathic Pain, Vienna; Cruccu, Giorgio; Aziz, T. Z.

    2007-01-01

    and to produce relevant recommendations. We searched the literature from 1968 to 2006, looking for neurostimulation in neuropathic pain conditions, and classified the trials according to the EFNS scheme of evidence for therapeutic interventions. Spinal cord stimulation (SCS) is efficacious in failed back surgery......Pharmacological relief of neuropathic pain is often insufficient. Electrical neurostimulation is efficacious in chronic neuropathic pain and other neurological diseases. European Federation of Neurological Societies (EFNS) launched a Task Force to evaluate the evidence for these techniques......TMS) has transient efficacy in central and peripheral neuropathic pains (level B). Motor cortex stimulation (MCS) is efficacious in central post-stroke and facial pain (level C). Deep brain stimulation (DBS) should only be performed in experienced centres. Evidence for implanted peripheral stimulations...

  8. Prevalence of Neuropathic Pain and the Need for Treatment

    Directory of Open Access Journals (Sweden)

    Pat Morley-Forster

    2006-01-01

    There is an unmet need for the treatment of neuropathic pain as evidenced by reports of pain despite the use of opioids and anticonvulsants, continuing psychological difficulties, lack of access to treatments and patients seeking access to complementary therapy.

  9. The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model

    Directory of Open Access Journals (Sweden)

    Sumizono M

    2018-02-01

    neuropathic pain was accelerated through the regulation of glial activation, BDNF expression, and the endogenous opioid system. The expression of BDNF and endogenous opioid in relation to exercise-induced alleviation of neuropathic pain differed in the HFE and LFE groups. The effects of exercise-induced alleviation of mechanical hypersensitivity were reversed by the administration of naloxone. Conclusion: The LFE and HFE program reduced neuropathic pain. Our findings indicated that aerobic exercise-induced alleviated neuropathic pain through the regulation of glial cell activation, expression of BDNF in the ipsilateral spinal dorsal horn, and the endogenous opioid system. Keywords: exercise, neuropathic pain, rehabilitation, glial cells, endogenous opioid

  10. [Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain].

    Science.gov (United States)

    Mylius, V; Ayache, S S; Teepker, M; Kappus, C; Kolodziej, M; Rosenow, F; Nimsky, C; Oertel, W H; Lefaucheur, J P

    2012-12-01

    Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

  11. Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

    OpenAIRE

    Ming Liu; Kaijun Liao; Changxi Yu; Xuejun Li; Suhuan Liu; Shuyu Yang

    2014-01-01

    Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM) ...

  12. Chronic Neuropathic Pain in Spinal Cord Injury: The Patient's Perspective

    Directory of Open Access Journals (Sweden)

    Penelope Henwood

    2004-01-01

    Full Text Available BACKGROUND: Chronic neuropathic pain (CNP in spinal cord injury (SCI is recognized as severely compromising, in both adjustment after injury and quality of life. Studies indicate that chronic pain in SCI is associated with great emotional distress over and above that of the injury itself. Currently, little is known about the SCI patient's perception of the impact of living with chronic neuropathic pain.

  13. An Algorithm for Neuropathic Pain Management in Older People

    OpenAIRE

    Pickering, Gis?le; Marcoux, Margaux; Chapiro, Sylvie; David, Laurence; Rat, Patrice; Michel, Micheline; Bertrand, Isabelle; Voute, Marion; Wary, Bernard

    2016-01-01

    Neuropathic pain frequently affects older people, who generally also have several comorbidities. Elderly patients are often poly-medicated, which increases the risk of drug?drug interactions. These patients, especially those with cognitive problems, may also have restricted communication skills, making pain evaluation difficult and pain treatment challenging. Clinicians and other healthcare providers need a decisional algorithm to optimize the recognition and management of neuropathic pain. W...

  14. Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation

    Directory of Open Access Journals (Sweden)

    Kelly Barbosa Gama

    2018-01-01

    Full Text Available Neuropathic pain is a type of chronic pain caused by injury or dysfunction of the nervous system, without effective therapeutic approaches. Mesenchymal stromal cells (MSCs, through their paracrine action, have great potential in the treatment of this syndrome. In the present study, the therapeutic potential of MSC-derived conditioned medium (CM was investigated in a mouse model of neuropathic pain induced by partial sciatic nerve ligation (PSL. PSL mice were treated by endovenous route with bone marrow-derived MSCs (1 × 106, CM, or vehicle. Gabapentin was the reference drug. Twelve hours after administration, neuropathic mice treated with CM exhibited an antinociceptive effect that was maintained throughout the evaluation period. MSCs also induced nonreversed antinociception, while gabapentin induced short-lasting antinociception. The levels of IL-1β, TNF-α, and IL-6 were reduced, while IL-10 was enhanced on sciatic nerve and spinal cord by treatment with CM and MSCs. Preliminary analysis of the CM secretome revealed the presence of growth factors and cytokines likely involved in the antinociception. In conclusion, the CM, similar to injection of live cells, produces a powerful and long-lasting antinociceptive effect on neuropathic pain, which is related with modulatory properties on peripheral and central levels of cytokines involved with the maintenance of this syndrome.

  15. Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

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    Ouyang Handong

    2011-05-01

    Full Text Available Abstract Background HIV-associated sensory neuropathy (HIV-SN is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS. The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. Results Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes and Iba1 (a marker of microglia in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia. Conclusions Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.

  16. Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats.

    Science.gov (United States)

    Dos Reis, Renata C; Kopruszinski, Caroline M; Nones, Carina F M; Chichorro, Juliana G

    2016-09-01

    There is preclinical evidence that nerve growth factor (NGF) contributes toward inflammatory hyperalgesia in the orofacial region, but the mechanisms underlying its hyperalgesic effect as well as its role in trigeminal neuropathic pain require further investigation. This study investigated the ability of NGF to induce facial heat hyperalgesia and the involvement of tyrosine kinase receptor A, transient receptor potential vanilloid 1, and mast cells in NGF pronociceptive effects. In addition, the role of NGF in heat hyperalgesia in a model of trigeminal neuropathic pain was evaluated. NGF injection into the upper lip of naive rats induced long-lasting heat hyperalgesia. Pretreatment with an antibody anti-NGF, antagonists of tyrosine kinase receptor A, and transient receptor potential vanilloid 1 receptors or compound 48/80, to induce mast-cell degranulation, all attenuated NGF-induced hyperalgesia. In a rat model of trigeminal neuropathic pain, local treatment with anti-NGF significantly reduced heat hyperalgesia. In addition, increased NGF levels were detected in the ipsilateral infraorbital nerve branch at the time point that represents the peak of heat hyperalgesia. The results suggest that NGF is a prominent hyperalgesic mediator in the trigeminal system and it may represent a potential therapeutic target for the management of painful orofacial conditions, including trigeminal neuropathic pain.

  17. The α2δ-1-NMDA Receptor Complex Is Critically Involved in Neuropathic Pain Development and Gabapentin Therapeutic Actions

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    Jinjun Chen

    2018-02-01

    Full Text Available α2δ-1, commonly known as a voltage-activated Ca2+ channel subunit, is a binding site of gabapentinoids used to treat neuropathic pain and epilepsy. However, it is unclear how α2δ-1 contributes to neuropathic pain and gabapentinoid actions. Here, we show that Cacna2d1 overexpression potentiates presynaptic and postsynaptic NMDAR activity of spinal dorsal horn neurons to cause pain hypersensitivity. Conversely, Cacna2d1 knockdown or ablation normalizes synaptic NMDAR activity increased by nerve injury. α2δ-1 forms a heteromeric complex with NMDARs in rodent and human spinal cords. The α2δ-1-NMDAR interaction predominantly occurs through the C terminus of α2δ-1 and promotes surface trafficking and synaptic targeting of NMDARs. Gabapentin or an α2δ-1 C terminus-interfering peptide normalizes NMDAR synaptic targeting and activity increased by nerve injury. Thus, α2δ-1 is an NMDAR-interacting protein that increases NMDAR synaptic delivery in neuropathic pain. Gabapentinoids reduce neuropathic pain by inhibiting forward trafficking of α2δ-1-NMDAR complexes.

  18. Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ya-Qiong [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Jin, Shao-Ju [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Luohe Medical College, Luohe 462002, Henan Province (China); Liu, Ning [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Li, Yu-Xiang [College of Nursing, Ningxia Medical University, Yinchuan 750004 (China); Zheng, Jie [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Ma, Lin [Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004 (China); Du, Juan; Zhou, Ru [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Zhao, Cheng-Jun [Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750000 (China); Niu, Yang [Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004 (China); Sun, Tao [Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004 (China); Yu, Jian-Qiang, E-mail: Yujq910315@163.com [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Luohe Medical College, Luohe 462002, Henan Province (China)

    2014-09-05

    Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.

  19. Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

    International Nuclear Information System (INIS)

    Xu, Ya-Qiong; Jin, Shao-Ju; Liu, Ning; Li, Yu-Xiang; Zheng, Jie; Ma, Lin; Du, Juan; Zhou, Ru; Zhao, Cheng-Jun; Niu, Yang; Sun, Tao; Yu, Jian-Qiang

    2014-01-01

    Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway

  20. A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sakamoto Atsuhiro

    2011-01-01

    Full Text Available Abstract Background Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown. Results Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF, which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain. Conclusions Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.

  1. Surgical experience of laparoscopic retroperitoneal triple neurectomy for a patient with chronic neuropathic inguinodynia

    Directory of Open Access Journals (Sweden)

    Masato Narita

    2017-01-01

    Conclusions: Laparoscopic retroperitoneal triple neurectomy is useful for treating refractory neuropathic pain. The diagnosis of neuropathic pain via thorough preoperative assessment is vital for procedure success because the procedure would not be effective for other types of pain.

  2. Mechanisms of disease: mechanism-based classification of neuropathic pain - a critical analysis

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Jensen, Troels Staehelin

    2006-01-01

    Classification of neuropathic pain according to etiology or localization has clear limitations. The discovery of specific molecular and cellular events following experimental nerve injury has raised the possibility of classifying neuropathic pain on the basis of the underlying neurobiological...

  3. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Han, Zee-A; Song, Dae Heon; Oh, Hyun-Mi; Chung, Myung Eun

    2016-04-01

    To evaluate the analgesic effect of botulinum toxin type A (BTX-A) on patients with spinal cord injury-associated neuropathic pain. The effect of BTX-A on 40 patients with spinal cord injury-associated neuropathic pain was investigated using a randomized, double-blind, placebo-controlled design. A 1-time subcutaneous BTX-A (200U) injection was administered to the painful area. Visual analogue scale (VAS) scores (0-100mm), the Korean version of the short-form McGill Pain Questionnaire, and the World Health Organization WHOQOL-BREF quality of life assessment were evaluated prior to treatment and at 4 and 8 weeks after the injection. At 4 and 8 weeks after injection, the VAS score for pain was significantly reduced by 18.6 ± 16.8 and 21.3 ± 26.8, respectively, in the BTX-A group, whereas it was reduced by 2.6 ± 14.6 and 0.3 ± 19.5, respectively, in the placebo group. The pain relief was associated with preservation of motor or sensory function below the neurological level of injury. Among the responders in the BTX-A group, 55% and 45% reported pain relief of 20% or greater at 4 and 8 weeks, respectively, after the injection, whereas only 15% and 10% of the responders in the placebo group reported a similar level of pain relief. Improvements in the score for the physical health domain of the WHOQOL-BREF in the BTX-A group showed a marginal trend toward significance (p = 0.0521) at 4 weeks after the injection. These results indicate that BTX-A may reduce intractable chronic neuropathic pain in patients with spinal cord injury. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

  4. D-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice.

    Science.gov (United States)

    Palazzo, Enza; Luongo, Livio; Guida, Francesca; Marabese, Ida; Romano, Rosaria; Iannotta, Monica; Rossi, Francesca; D'Aniello, Antimo; Stella, Luigi; Marmo, Federica; Usiello, Alessandro; de Bartolomeis, Andrea; Maione, Sabatino; de Novellis, Vito

    2016-07-01

    D-Aspartate (D-Asp) is a free D-amino acid detected in multiple brain regions and putative precursor of endogenous N-methyl-D-aspartate (NMDA) acting as agonist at NMDA receptors. In this study, we investigated whether D-Asp (20 mM) in drinking solution for 1 month affects pain responses and pain-related emotional, and cognitive behaviour in a model of neuropathic pain induced by the spared nerve injury (SNI) of the sciatic nerve in mice. SNI mice developed mechanical allodynia and motor coordination impairment 30 days after SNI surgery. SNI mice showed cognitive impairment, anxiety and depression-like behaviour, reduced sociability in the three chamber sociability paradigm, increased expression of NR2B subunit of NMDA receptor and Homer 1a in the medial prefrontal cortex (mPFC). The expression of (post synaptic density) PSD-95 and Shank 1was instead unaffected in the mPFC of the SNI mice. Treatment with D-Asp drinking solution, started right after the SNI (day 0), alleviated mechanical allodynia, improved cognition and motor coordination and increased social interaction. D-Asp also restored the levels of extracellular D-Asp, Homer 1a and NR2B subunit of the NMDA receptor to physiological levels and reduced Shank1 and PSD-95 protein levels in the mPFC. Amitriptyline, a tricyclic antidepressant used also to alleviate neuropathic pain in humans, reverted mechanical allodynia and cognitive impairment, and unlike D-Asp, was effective in reducing depression and anxiety-like behaviour in the SNI mice and increased PSD protein level. Altogether these findings demonstrate that D-Asp improves sensorial, motor and cognitive-like symptoms related to chronic pain possibly through glutamate neurotransmission normalization in neuropathic mice.

  5. The evidence for pharmacological treatment of neuropathic pain.

    Science.gov (United States)

    Finnerup, Nanna Brix; Sindrup, Søren Hein; Jensen, Troels Staehelin

    2010-09-01

    Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids are the drug classes for which there is the best evidence for a clinical relevant effect. Despite a 66% increase in published trials only a limited improvement of neuropathic pain treatment has been obtained. A large proportion of neuropathic pain patients are left with insufficient pain relief. This fact calls for other treatment options to target chronic neuropathic pain. Large-scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism-based classification may help improve treatment of the individual patients. Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. Population pharmacokinetics of tamsulosin hydrochloride in paediatric patients with neuropathic and non-neuropathic bladder

    Science.gov (United States)

    Tsuda, Yasuhiro; Tatami, Shinji; Yamamura, Norio; Tadayasu, Yusuke; Sarashina, Akiko; Liesenfeld, Karl-Heinz; Staab, Alexander; Schäfer, Hans-Günter; Ieiri, Ichiro; Higuchi, Shun

    2010-01-01

    AIMS The main objective of this study was to characterize the population pharmacokinetics of tamsulosin hydrochloride (HCl) in paediatric patients with neuropathic and non-neuropathic bladder. A secondary objective was to compare the pharmacokinetics in paediatric patients and adults. METHODS Tamsulosin HCl plasma concentrations in 1082 plasma samples from 189 paediatric patients (age range 2–16 years) were analyzed with NONMEM, applying a one compartment model with first-order absorption. Based on the principles of allometry, body weight was incorporated in the base model, along with fixed allometric exponents. Covariate analysis was performed by means of a stepwise forward inclusion and backward elimination procedure. Simulations based on the final model were used to compare the pharmacokinetics with those in adults. RESULTS Beside the priori-implemented body weight, only α1-acid glycoprotein had an effect on both apparent clearance and apparent volume of distribution. No other investigated covariates, including gender, age, race, patient population and concomitant therapy with anti-cholinergics, significantly affected the pharmacokinetics of tamsulosin HCl (P tamsulosin HCl in paediatric patients was established and it described the data well. There was no major difference in the pharmacokinetics of tamsulosin HCl between paediatric patients (age range 2–16 years) and adults when the effect of body weight was taken into consideration. PMID:20642551

  7. Trigeminal nerve anatomy in neuropathic and non-neuropathic orofacial pain patients.

    Science.gov (United States)

    Wilcox, Sophie L; Gustin, Sylvia M; Eykman, Elizabeth N; Fowler, Gordon; Peck, Christopher C; Murray, Greg M; Henderson, Luke A

    2013-08-01

    Trigeminal neuralgia, painful trigeminal neuropathy, and painful temporomandibular disorders (TMDs) are chronic orofacial pain conditions that are thought to have fundamentally different etiologies. Trigeminal neuralgia and neuropathy are thought to arise from damage to or pressure on the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. This study sought to assess the volume and microstructure of the trigeminal nerve in these 3 conditions. In 9 neuralgia, 18 neuropathy, 20 TMD, and 26 healthy controls, the trigeminal root entry zone was selected on high-resolution T1-weighted magnetic resonance images and the volume (mm(3)) calculated. Additionally, using diffusion-tensor images (DTIs), the mean diffusivity and fractional anisotropy values of the trigeminal nerve root were calculated. Trigeminal neuralgia patients displayed a significant (47%) decrease in nerve volume but no change in DTI values. Conversely, trigeminal neuropathy subjects displayed a significant (40%) increase in nerve volume but again no change in DTI values. In contrast, TMD subjects displayed no change in volume or DTI values. The data suggest that the changes occurring within the trigeminal nerve are not uniform in all orofacial pain conditions. These structural and volume changes may have implications in diagnosis and management of different forms of chronic orofacial pain. This study reveals that neuropathic orofacial pain conditions are associated with changes in trigeminal nerve volume, whereas non-neuropathic orofacial pain is not associated with any change in nerve volume. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  8. Neuropathic Minimally Invasive Surgeries (NEMESIS):: Percutaneous Diabetic Foot Surgery and Reconstruction.

    Science.gov (United States)

    Miller, Roslyn J

    2016-09-01

    Patients with peripheral neuropathy associated with ulceration are the nemesis of the orthopedic foot and ankle surgeon. Diabetic foot syndrome is the leading cause of peripheral neuropathy, and its prevalence continues to increase at an alarming rate. Poor wound healing, nonunion, infection, and risk of amputation contribute to the understandable caution toward this patient group. Significant metalwork is required to hold these technically challenging deformities. Neuropathic Minimally Invasive Surgeries is an addition to the toolbox of management of the diabetic foot. It may potentially reduce the risk associated with large wounds and bony correction in this patient group. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats.

    Science.gov (United States)

    Mixcoatl-Zecuatl, Teresa; Quinonez-Bastidas, Geovanna N; Caram-Salas, Nadia L; Ambriz-Tututi, Monica; Araiza-Saldana, Claudia I; Rocha-Gonzalez, Hector I; Medina-Santillan, Roberto; Reyes-Garcia, Gerardo; Granados-Soto, Vinicio

    2008-01-01

    Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans.

  10. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Ombretta Caspani

    Full Text Available Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  11. Neuropathic Pain Following Poly-L-Lactic Acid (Sculptra) Injection.

    Science.gov (United States)

    Vrcek, Ivan; El-Sawy, Tarek; Chou, Eva; Allen, Theresa; Nakra, Tanuj

    Injectable fillers have become a prevalent means of facial rejuvenation and volume expansion. While typically well tolerated, serious complications have been reported. The authors present a case in which an otherwise healthy female with a history of multiple filler injections including poly-L-lactic acid, developed 3 weeks of neuropathic pain in the left temporal fossa following injection. To the best of the authors knowledge, neuropathic pain has not been reported as a complication following poly-L-lactic acid injection. The patient was treated with an injection of steroid and long-acting anesthetic with resolution of symptoms.

  12. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

    Directory of Open Access Journals (Sweden)

    Domenico Intiso

    2015-06-01

    Full Text Available Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders

  13. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

    Science.gov (United States)

    Intiso, Domenico; Basciani, Mario; Santamato, Andrea; Intiso, Marta; Di Rienzo, Filomena

    2015-01-01

    Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP) results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX) as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders including post

  14. Probiotics for preventing urinary tract infection in people with neuropathic bladder.

    Science.gov (United States)

    Toh, Swee-Ling; Boswell-Ruys, Claire L; Lee, Bon San B; Simpson, Judy M; Clezy, Kate R

    2017-09-08

    Neuropathic or neurogenic bladder describes a process of dysfunctional voiding as the result of injury in the brain, spinal cord or nerves innervating the bladder. People with neuropathic bladder, such as from spinal cord injury (SCI), are at significant risk of morbidity from urinary tract infections (UTI). Effective methods to prevent UTI in people with SCI have been sought for many years. Probiotics (micro-organisms that exert beneficial health effects in the host) have been recommended for bacterial interference of the urological tract to reduce colonisation by uropathogen and to manage the dual problems of infection and antibiotic resistance. This review looked at the benefits and harms of probiotics in preventing symptomatic UTI in people with neuropathic bladder compared with placebo, no therapy, or non-antibiotic prophylaxis (cranberry juice, methenamine hippurate, topical oestrogen). We searched the Cochrane Kidney and Transplant Specialised Register up to 10 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. All randomised controlled trials (RCTs), quasi-RCTs and cross-over RCTs looking at the use of probiotics for the prophylaxis of UTI in people with neuropathic bladders was considered for inclusion. Men, women and children of all ages with neuropathic bladders from neurological injury such as suprapontine, supra sacral and sacral aetiologies was included. All bladder management types, including reflex voiding, time voiding, indwelling and intermittent catheterization were eligible for this review.Studies comparing probiotics to placebo, no treatment or other non-antibiotic prophylaxis was included. Studies comparing probiotics with antibiotics or in combination with antibiotics were

  15. The effects of transcranial direct current stimulation in patients with neuropathic pain from spinal cord injury.

    Science.gov (United States)

    Ngernyam, Niran; Jensen, Mark P; Arayawichanon, Preeda; Auvichayapat, Narong; Tiamkao, Somsak; Janjarasjitt, Suparerk; Punjaruk, Wiyada; Amatachaya, Anuwat; Aree-uea, Benchaporn; Auvichayapat, Paradee

    2015-02-01

    Transcranial direct current stimulation (tDCS) has demonstrated efficacy for reducing neuropathic pain, but the respective mechanisms remain largely unknown. The current study tested the hypothesis that pain reduction with tDCS is associated with an increase in the peak frequency spectrum density in the theta-alpha range. Twenty patients with spinal cord injury and bilateral neuropathic pain received single sessions of both sham and anodal tDCS (2 mA) over the left primary motor area (M1) for 20 min. Treatment order was randomly assigned. Pre- to post-procedure changes in pain intensity and peak frequency of electroencephalogram spectral analysis were compared between treatment conditions. The active treatment condition (anodal tDCS over M1) but not sham treatment resulted in significant decreases in pain intensity. In addition, consistent with the study hypothesis, peak theta-alpha frequency (PTAF) assessed from an electrode placed over the site of stimulation increased more from pre- to post-session among participants in the active tDCS condition, relative to those in the sham tDCS condition. Moreover, we found a significant association between a decrease in pain intensity and an increase in PTAF at the stimulation site. The findings are consistent with the possibility that anodal tDCS over the left M1 may be effective, at least in part, because it results in an increase in M1 cortical excitability, perhaps due to a pain inhibitory effect of motor cortex stimulation that may influence the descending pain modulation system. Future research is needed to determine if there is a causal association between increased left anterior activity and pain reduction. The results provide new findings regarding the effects of tDCS on neuropathic pain and brain oscillation changes. Copyright © 2014 International Federation of Clinical Neurophysiology. All rights reserved.

  16. A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury.

    Science.gov (United States)

    Cardenas, Diana D; Nieshoff, Edward C; Suda, Kota; Goto, Shin-Ichi; Sanin, Luis; Kaneko, Takehiko; Sporn, Jonathan; Parsons, Bruce; Soulsby, Matt; Yang, Ruoyong; Whalen, Ed; Scavone, Joseph M; Suzuki, Makoto M; Knapp, Lloyd E

    2013-02-05

    To assess the efficacy and tolerability of pregabalin for the treatment of central neuropathic pain after spinal cord injury (SCI). Patients with chronic, below-level, neuropathic pain due to SCI were randomized to receive 150 to 600 mg/d pregabalin (n = 108) or matching placebo (n = 112) for 17 weeks. Pain was classified in relation to the neurologic level of injury, defined as the most caudal spinal cord segment with normal sensory and motor function, as above, at, or below level. The primary outcome measure was duration-adjusted average change in pain. Key secondary outcome measures included the change in mean pain score from baseline to end point, the percentage of patients with ≥30% reduction in mean pain score at end point, patient global impression of change scores at end point, and the change in mean pain-related sleep interference score from baseline to end point. Additional outcome measures included the medical outcomes study-sleep scale and the Hospital anxiety and depression scale. Pregabalin treatment resulted in statistically significant improvements over placebo for all primary and key secondary outcome measures. Significant pain improvement was evident as early as week 1 and was sustained throughout the treatment period. Adverse events were consistent with the known safety profile of pregabalin and were mostly mild to moderate in severity. Somnolence and dizziness were most frequently reported. This study demonstrates that pregabalin is effective and well tolerated in patients with neuropathic pain due to SCI. This study provides class I evidence that pregabalin, 150 to 600 mg/d, is effective in reducing duration-adjusted average change in pain compared with baseline in patients with SCI over a 16-week period (p = 0.003, 95% confidence interval = -0.98, -0.20).

  17. The mechanism of neurofeedback training for treatment of central neuropathic pain in paraplegia: a pilot study.

    Science.gov (United States)

    Hassan, Muhammad Abul; Fraser, Matthew; Conway, Bernard A; Allan, David B; Vuckovic, Aleksandra

    2015-10-13

    Central neuropathic pain has a prevalence of 40% in patients with spinal cord injury. Electroencephalography (EEG) studies showed that this type of pain has identifiable signatures, that could potentially be targeted by a neuromodulation therapy. The aim of the study was to investigate the putative mechanism of neurofeedback training on central neuropathic pain and its underlying brain signatures in patients with chronic paraplegia. Patients' EEG activity was modulated from the sensory-motor cortex, electrode location C3/Cz/C4/P4 in up to 40 training sessions Results. Six out of seven patients reported immediate reduction of pain during neurofeedback training. Best results were achieved with suppressing Ɵ and higher β (20-30 Hz) power and reinforcing α power at C4. Four patients reported clinically significant long-term reduction of pain (>30%) which lasted at least a month beyond the therapy. EEG during neurofeedback revealed a wide spread modulation of power in all three frequency bands accompanied with changes in the coherence most notable in the beta band. The standardized low resolution electromagnetic tomography analysis of EEG before and after neurofeedback therapy showed the statistically significant reduction of power in beta frequency band in all tested patients. Areas with reduced power included the Dorsolateral Prefrontal Cortex, the Anterior Cingulate Cortex and the Insular Cortex. Neurofeedback training produces both immediate and longer term reduction of central neuropathic pain that is accompanied with a measurable short and long term modulation of cortical activity. Controlled trials are required to confirm the efficacy of this neurofeedback protocol on treatment of pain. The study is a registered UKCRN clinical trial Nr 9824.

  18. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Elphick Maurice R

    2009-07-01

    Full Text Available Abstract Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG, and the related compound N-palmitoylethanolamine (PEA, in neuropathic spinal cord. Selective spinal nerve ligation (SNL in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P P P P P

  19. Effect of styrene maleic acid WIN55,212-2 micelles on neuropathic pain in a rat model.

    Science.gov (United States)

    Linsell, Oliver; Brownjohn, Philip W; Nehoff, Hayley; Greish, Khaled; Ashton, John C

    2015-05-01

    Cannabinoid receptor agonists are moderately effective at reducing neuropathic pain but are limited by psychoactivity. We developed a styrene maleic acid (SMA) based on the cannabinoid WIN 55,212-2 (WIN) and tested in a rat model of neuropathic pain and in the rotarod test. We hypothesized that miceller preparation can ensure prolonged plasma half-life being above the renal threshold of excretion. Furthermore, SMA-WIN could potentially reduce the central nervous system effects of encapsulated WIN by limiting its transport across the blood-brain barrier. Using the chronic constriction injury model of sciatic neuropathy, the SMA-WIN micelles were efficacious in the treatment of neuropathic pain for a prolonged period compared to control (base WIN). Attenuation of chronic constriction injury-induced mechanical allodynia occurred for up to 8 h at a dose of 11.5 mg/kg of SMA-WIN micelles. To evaluate central effects on motor function, the rotarod assessment was utilized. Results showed initial impairment caused by SMA-WIN micelles to be identical to WIN control for up to 1.5 h. Despite this, the SMA-WIN micelle formulation was able to produce prolonged analgesia over a time when there was decreased impairment in the rotarod test compared with base WIN.

  20. Minocycline Enhances the Effectiveness of Nociceptin/Orphanin FQ during Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Katarzyna Popiolek-Barczyk

    2014-01-01

    Full Text Available Nociceptin/orphanin FQ (N/OFQ antinociception, which is mediated selectively by the N/OFQ peptide receptor (NOP, was demonstrated in pain models. In this study, we determine the role of activated microglia on the analgesic effects of N/OFQ in a rat model of neuropathic pain induced by chronic constriction injury (CCI to the sciatic nerve. Repeated 7-day administration of minocycline (30 mg/kg i.p., a drug that affects microglial activation, significantly reduced pain in CCI-exposed rats and it potentiates the analgesic effects of administered N/OFQ (2.5–5 μg i.t.. Minocycline also downregulates the nerve injury-induced upregulation of NOP protein in the dorsal lumbar spinal cord. Our in vitro study showed that minocycline reduced NOP mRNA, but not protein, level in rat primary microglial cell cultures. In [35S]GTPγS binding assays we have shown that minocycline increases the spinal N/OFQ-stimulated NOP signaling. We suggest that the modulation of the N/OFQ system by minocycline is due to the potentiation of its neuronal antinociceptive activity and weakening of the microglial cell activation. This effect is beneficial for pain relief, and these results suggest new targets for the development of drugs that are effective against neuropathic pain.

  1. ARA290 : a novel treatment for neuropathic pain in sarcoidosis

    NARCIS (Netherlands)

    Heij, L.

    2016-01-01

    The general aim of this thesis is to investigate small fiber neuropathy in sarcoidosis and to asses whether ARA290 is a possible new agent to treat the neuropathic complaints in sarcoidosis population. The results of the various ARA290 trials in painful sarcoidosis are discussed. Painful neuropathy

  2. Neuropathic Pain - Current Concepts | Meyer | South African Family ...

    African Journals Online (AJOL)

    Neuropathic pain (NP) represents a common and diverse group of disorders with peripheral and/or central nervous system damage or dysfunction. Many patients report intractable and severe pain that is resistant to simple analgesics. The diagnosis of NP is primarily based on clinical evaluation rather than diagnostic tests.

  3. Neuropathic pain and spasticity: intricate consequences of spinal cord injury

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix

    2017-01-01

    of SCI, and a careful examination and characterization of the symptoms and signs, are a prerequisite for understanding the relationship between neuropathic pain and spasticity and the intricate underlying mechanisms.Spinal Cord advance online publication, 11 July 2017; doi:10.1038/sc.2017.70....

  4. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

  5. Spinal cord stimulation and modulation of neuropathic pain

    NARCIS (Netherlands)

    de Vos, Cecilia Cecilia Clementine

    2013-01-01

    This thesis reports on the opportunities of several new applications of spinal cord stimulation (SCS) for the treatment of neuropathic pain. Our pilot study and consecutively performed international randomised controlled trial on effects of SCS in patients with painful diabetic neuropathy showed

  6. Elucidation of pathophysiology and treatment of neuropathic pain

    NARCIS (Netherlands)

    Vranken, Jan H.

    2012-01-01

    Neuropathic pain, pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, is relatively common, occurring in about 1% of the population. Studies in animal models describe a number of peripheral and central pathophysiological processes after nerve injury that

  7. Mortality associated with acute Charcot foot and neuropathic foot ulceration

    NARCIS (Netherlands)

    van Baal, Juliette; Hubbard, Richard; Game, Fran; Jeffcoate, William

    2010-01-01

    To compare the mortality of patients with an acute Charcot foot with a matched population with uninfected neuropathic foot ulcers (NFUs). Data were extracted from a specialist departmental database, supplemented by hospital records. The findings were compared with the results of earlier populations

  8. Low-dose vaporized cannabis significantly improves neuropathic pain.

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-02-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

  9. Neuropathic pain in people with cancer (part 2): pharmacological and non-pharmacological management.

    Science.gov (United States)

    Taverner, Tarnia

    2015-08-01

    The aim of this paper is to provide an overview of the management of neuropathic pain associated with cancer and to provide helpful clinical advice for nurses working with patients who may have neuropathic pain. While cancer pain is a mixed-mechanism pain, this article will focus only on neuropathic pain management. The impact of neuropathic pain on patients' quality of life is great and while many patients recover from their cancer, a significant number continue to suffer from a neuropathic pain syndrome. Management of neuropathic pain is significantly different from management of nociceptive pain with respect to pharmacological and non-pharmacological strategies. Neuropathic pain is complex, and as such requires complex management using pharmacological as well as non-pharmacological approaches. Specific drugs for neuropathic pain may be effective for some patients, but not all; therefore, ongoing and comprehensive assessment and management are required. Furthermore, these patients may require trials of several drugs before they find one that works for them. It is important for nurses to understand neuropathic pain, its manifestation, impact on quality of life and management when nursing patients with neuropathic pain associated with cancer.

  10. Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

    Science.gov (United States)

    Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

    2018-07-04

    Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

  11. Does a Rehabilitation Program of Aerobic and Progressive Resisted Exercises Influence HIV-Induced Distal Neuropathic Pain?

    Science.gov (United States)

    Maharaj, Sonill S; Yakasai, Abdulsalam M

    2018-05-01

    Distal symmetrical polyneuropathy is a common neurological sequela after HIV, which leads to neuropathic pain and functional limitations. Rehabilitation programs with exercises are used to augment pharmacological therapy to relieve pain but appropriate and effective exercises are unknown. This study explored the safety and effect of moderate-intensity aerobic exercises and progressive resisted exercises for HIV-induced distal symmetrical polyneuropathy neuropathic pain. A randomized pretest, posttest of 12 wks of aerobic exercise or progressive resisted exercise compared with a control. Outcome measures were assessed using the subjective periphery neuropathy, brief peripheral neuropathy screening, and numeric pain rating scale. Pain was assessed at baseline, 6 and 12 wks. Data between groups were compared using Kruskal-Wallis, Mann-Whitney U test, and within-groups Friedman and Wilcoxon signed rank tests. There were 136 participants (mean [SD] age = 36.79 [8.23] yrs) and the exercise groups completed the protocols without any adverse effects. Pain scores within and between aerobic exercise and progressive resisted exercise groups showed significant improvement (P 0.05). This study supports a rehabilitation program of moderate-intensity aerobic exercise and progressive resisted exercise being safe and effective for reducing neuropathic pain and is beneficial with analgesics for HIV-induced distal symmetrical polyneuropathy.

  12. An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

    2016-09-01

    Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model.

    Science.gov (United States)

    Farghaly, Hanan Sm; Abd-Ellatief, Rasha B; Moftah, Marie Z; Mostafa, Mostafa G; Khedr, Eman M; Kotb, Hassan I

    2014-01-01

    Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Multidrug therapy is potentially valuable to decrease side effects. The aim of the present study was to investigate the possible antinociceptive effect of dexmedetomidine, an α2-adrenoceptor agonist, and its combination with front-line treatment of neuropathic pain, i.e., amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the sciatic nerve in rats. Controlled animal study. Following unilateral ligation of the left sciatic nerve, the effect of intraperitoneal (i.p.) dexmedetomidine (5 ug/kg), tramadol (5 mg/kg), and amitriptyline (30 mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and hyperalgesia (measured by Randall and Selitto test) was studied. The sham-operated rats and un-operated hind paw (right paw) press normally on the floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests confirmed the development of neuropathic pain after CCI. All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine, amitriptyline, tramadol, amitriptyline+dexmedetomidine, and tramadol+dexmedetomidine combination did not produce any sedation/motor impairment (P > 0.05). Although the combination of these drugs improved the CCI model of neuropathic pain in this study, an additional interpretation of the underlying mechanism(s) will be needed to confirm these findings. The combination of these drugs appears to be more effective in increasing the pain threshold after peripheral nerve injury, when compared with the administration of either of amitriptyline or tramadol alone and should be considered as a possible alternative to decrease side effects of

  14. Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.

    Science.gov (United States)

    Zhao, Xin; Li, Xin-Lin; Liu, Xin; Wang, Chuang; Zhou, Dong-Sheng; Ma, Qing; Zhou, Wen-Hua; Hu, Zhen-Yu

    2015-12-01

    Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Fisetin, a naturally occurring flavonoid, has been reported to exert antidepressant-like effect in previous studies. As antidepressant drugs are employed clinically to treat neuropathic pain, this work aimed to investigate whether fisetin possess beneficial effect on diabetic neuropathic pain and explore the mechanism(s). We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (200mg/kg), and von Frey test or Hargreaves test was used to assess mechanical allodynia or thermal hyperalgesia, respectively. Chronic treatment of diabetic mice with fisetin not only ameliorated the established symptoms of thermal hyperalgesia and mechanical allodynia, but also arrested the development of neuropathic pain when given at low doses. Although chronic fisetin administration did not impact on the symptom of hyperglycemia in diabetic mice, it reduced exacerbated oxidative stress in tissues of spinal cord, dorsal root ganglion (DRG) and sciatic verve. Furthermore, the analgesic actions of fisetin were abolished by repetitive co-treatment with the reactive oxygen species (ROS) donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the ROS scavenger phenyl-N-tert-butylnitrone (PBN). Finally, acute blockade of spinal GABAA receptors by bicuculline totally counteracted such fisetin analgesia. These findings indicate that chronic fisetin treatment can delay or correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the present fisetin analgesia may be associated with its antioxidant activity, and spinal GABAA receptors are likely rendered as downstream targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Minocycline Effects on IL-6 Concentration in Macrophage and Microglial Cells in a Rat Model of Neuropathic Pain.

    Science.gov (United States)

    Moini-Zanjani, Taraneh; Ostad, Seyed-Nasser; Labibi, Farzaneh; Ameli, Haleh; Mosaffa, Nariman; Sabetkasaei, Masoumeh

    2016-11-01

    Evidence indicates that neuropathic pain pathogenesis is not confined to changes in the activity of neuronal systems but involves interactions between neurons, inflammatory immune and immune-like glial cells. Substances released from immune cells during inflammation play an important role in development and maintenance of neuropathic pain. It has been found that minocycline suppresses the development of neuropathic pain. Here, we evaluated the analgesic effect of minocycline in a chronic constriction injury (CCI) model of neuropathic pain in rat and assessed IL-6 concentration from cultured macrophage and microglia cells. Male Wistar rat (n=6, 150-200 g) were divided into three different groups: 1) CCI+vehicle, 2) sham+vehicle, and 3) CCI+drug. Minocycline (10, 20, and 40 mg/kg) was injected one hour before surgery and continued daily to day 14 post ligation. Von Frey filaments and acetone, as pain behavioral tests, were used for mechanical allodynia and cold allodynia, respectively. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7, 10, and 14 post -injury. At day 14, rats were killed and monocyte-derived macrophage from right ventricle and microglia from lumbar part of the spinal cord were isolated and cultured in RPMI and Leibovitz's media, respectively. IL-6 concentration was evaluated in cell culture supernatant after 24 h. Minocycline (10, 20, and 40 mg/kg) attenuated pain behavior, and a decrease in IL-6 concentration was observed in immune cells compared to CCI vehicle-treated animals. Minocycline reduced pain behavior and decreased IL-6 concentration in macrophage and microglial cells.

  16. Topical patches as treatments for the management of patient musculoskeletal and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Simona Mirel

    2017-02-01

    Full Text Available The variety and multiple dimensions of pain (acute/chronic, mild/moderate/severe, nociceptive/neuropathic requires different pharmacologic and non-pharmacologic treatments in certain patients. A lot of topical formulation, from various therapeutic classes have been proposed in order to decrease systemic exposure and to reduce the risks of adverse events. Topical as well as transdermal drug delivery systems are proposed as medicated plasters with: anesthetics (lidocaine, analgesic or nonsteroidal anti-inflamatory drugs (NSAIDs, alone or co-formulated. Capsaicin, salicylates, menthol and camphor represent the counterirritant class of topical analgesics used as patch active compounds. These compounds produce their analgesic effect by activating and desensitizing epidermal nociceptors. The most used topical treatment in order to decrease pain is the application of cold and heat patches - by acting directly on the affected tissue. In many cases there is a limited number of studies providing insufficient information to clinicians in order to evaluate the benefits of these products. This paper reviews the use and efficacy of available self-adhesing occlusive medicated plaster (pain patches that might represent an alternative option for the management of patient pain, specially in the case of musculoskeletal and neuropathic disorders.

  17. Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC class II.

    Science.gov (United States)

    Hartlehnert, Maike; Derksen, Angelika; Hagenacker, Tim; Kindermann, David; Schäfers, Maria; Pawlak, Mathias; Kieseier, Bernd C; Meyer Zu Horste, Gerd

    2017-10-02

    The activation of T helper cells requires antigens to be exposed on the surface of antigen presenting cells (APCs) via MHC class II (MHC-II) molecules. Expression of MHC-II is generally limited to professional APCs, but other cell types can express MHC-II under inflammatory conditions. However, the importance of these conditional APCs is unknown. We and others have previously shown that Schwann cells are potentially conditional APCs, but the functional relevance of MHC-II expression by Schwann cells has not been studied in vivo. Here, we conditionally deleted the MHC-II β-chain from myelinating Schwann cells in mice and investigated how this influenced post-traumatic intraneural inflammation and neuropathic pain using the chronic constriction injury (CCI) model. We demonstrate that deletion of MHC-II in myelinating Schwann cells reduces thermal hyperalgesia and, to a lesser extent, also diminishes mechanical allodynia in CCI in female mice. This was accompanied by a reduction of intraneural CD4+ T cells and greater preservation of preferentially large-caliber axons. Activation of T helper cells by MHC-II on Schwann cells thus promotes post-traumatic axonal loss and neuropathic pain. Hence, we provide experimental evidence that Schwann cells gain antigen-presenting function in vivo and modulate local immune responses and diseases in the peripheral nerves.

  18. Circuitry and plasticity of the dorsal horn--toward a better understanding of neuropathic pain.

    Science.gov (United States)

    West, S J; Bannister, K; Dickenson, A H; Bennett, D L

    2015-08-06

    Maladaptive plasticity within the dorsal horn (DH) of the spinal cord is a key substrate for development of neuropathic pain following peripheral nerve injury. Advances in genetic engineering, tracing techniques and opto-genetics are leading to a much better understanding of the complex circuitry of the spinal DH and the radical changes evoked in such circuitry by nerve injury. These changes can be viewed at multiple levels including: synaptic remodeling including enhanced excitatory and reduced inhibitory drive, morphological and electrophysiological changes which are observed both to primary afferent inputs as well as DH neurons, and ultimately circuit-level rewiring which leads to altered connectivity and aberrant processing of sensory inputs in the DH. The DH should not be seen in isolation but is subject to important descending modulation from the brainstem, which is further dysregulated by nerve injury. Understanding which changes relate to specific disease-states is essential, and recent work has aimed to stratify patient populations in a mechanistic fashion. In this review we will discuss how such pathophysiological mechanisms may lead to the distressing sensory phenomena experienced by patients suffering neuropathic pain, and the relationship of such mechanisms to current and potential future treatment modalities. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice.

    Science.gov (United States)

    Zhang, Qian; Cao, De-Li; Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

    2016-07-11

    Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the trigeminal ganglion (TG) mediates orofacial pain are unknown. The partial infraorbital nerve ligation (pIONL) was used to induce trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 (-/-) mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-α and IL-1β upregulation induced by pIONL. TNF-α inhibitor (Etanercept) and IL-1β inhibitor (Diacerein) attenuated pIONL-induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-α and IL-1β in the TG of WT mice, but not in Cxcr5 (-/-) mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-α and IL-1β upregulation. CXCL13 and CXCR5 contribute to orofacial pain via ERK-mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain.

  20. Transient urinary retention and chronic neuropathic pain associated with genital herpes simplex virus infection.

    Science.gov (United States)

    Haanpää, Maija; Paavonen, Jorma

    2004-10-01

    Genital herpes (GH) causes genital ulcer disease, severe transient pain, and often paresthesias. Whether or not GH can cause urinary retention or chronic neuropathic pain is not well known. We present two immunocompetent patients with GH associated with neuropathic symptoms. We also review the literature on GH and associated neurologic problems. Patient 1 had primary herpes simplex virus (HSV)-2 infection with transient urinary retention and chronic bilateral neuropathic pain in the sacral area. Patient 2 had recurrent HSV-1 associated with unitaleral chronic neuropathic pain in the sacral area. Although transient urinary retention associated with GH is not uncommon, chronic neuropathic pain has not been reported previously. Our cases show that chronic neuropathic pain, that is "pain initiated or caused by a primary lesion or dysfunction in the nervous system," can follow genital HSV infection.

  1. Spinal CPEB-mtROS-CBP signaling pathway contributes to perineural HIV gp120 with ddC-related neuropathic pain in rats.

    Science.gov (United States)

    Iida, Takafumi; Yi, Hyun; Liu, Shue; Huang, Wan; Kanda, Hirotsugu; Lubarsky, David A; Hao, Shuanglin

    2016-07-01

    Human immunodeficiency virus (HIV) patients treated with nucleoside reverse transcriptase inhibitors (NRTIs), have been known to develop neuropathic pain. While there has been a major shift away from some neurotoxic NRTIs in current antiretroviral therapy, a large number of HIV patients alive today have previously received them, and many have developed painful peripheral neuropathy. The exact mechanisms by which HIV with NRTIs contribute to the development of neuropathic pain are not known. Previous studies suggest that cytoplasmic polyadenylation element-binding protein (CPEB), reactive oxygen species (ROS), and cAMP-response element-binding protein (CREB)-binding protein (CBP), are involved in the neuroimmunological diseases including inflammatory/neuropathic pain. In this study, we investigated the role of CPEB, mitochondrial ROS (mtROS), or CBP in neuropathic pain induced by HIV envelope protein gp120 combined with antiretroviral drug. The application of recombinant gp120 into the sciatic nerve plus systemic ddC (one of NRTIs) induced mechanical allodynia. Knockdown of CPEB or CBP using intrathecal antisense oligodeoxynucleotide (AS-ODN) reduced mechanical allodynia. Intrathecal mitochondrial superoxide scavenger mito-tempol (Mito-T) increased mechanical withdrawal threshold. Knockdown of CPEB using intrathecal AS-ODN, reduced the up-regulated mitochondrial superoxide in the spinal dorsal horn in rats with gp120 combined with ddC. Intrathecal Mito-T lowered the increased expression of CBP in the spinal dorsal horn. Immunostaining studies showed that neuronal CPEB positive cells were co-localized with MitoSox positive profiles, and that MitoSox positive profiles were co-localized with neuronal CBP. Our studies suggest that neuronal CPEB-mtROS-CBP pathway in the spinal dorsal horn, plays an important role in the gp120/ddC-induced neuropathic pain in rats. Copyright © 2016. Published by Elsevier Inc.

  2. Macrophage-to-sensory neuron crosstalk mediated by Angiotensin II type-2 receptor elicits neuropathic pain

    OpenAIRE

    Krause, Eric; Shepherd, Andrew; Mickle, Aaron; Copits, Bryan; Karlsson, Pall; Kadunganattil, Suraj; Golden, Judith; Tadinada, Satya; Mack, Madison; Haroutounian, Simon; De Kloet, Annette; Samineni, Vijay; Valtcheva, Manouela; Mcilvried, Lisa; Sheahan, Tayler

    2017-01-01

    Peripheral nerve damage initiates a complex series of cellular and structural processes that culminate in chronic neuropathic pain. Our study defines local angiotensin signaling via activation of the Angiotensin II (Ang II) type-2 receptor (AT2R) on macrophages as the critical trigger of neuropathic pain. An AT2R-selective antagonist attenuates neuropathic, but not inflammatory pain hypersensitivity in mice, and requires the cell damage-sensing ion channel transient receptor potential family-...

  3. Effects of fisetin on oxaliplatin-induced neuropathic pain in mice

    OpenAIRE

    Hong Liu; Chaohua Wang; Hua Yang; Fengjie Wang

    2015-01-01

    Common chemotherapeutic agents such as oxaliplatin often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is difficult to treat and responds poorly to common analgesics, which represents a challenging clinical issue. Fisetin is a naturally occurring flavonoid and this study tested the potential anti-hyperalgesic effects of fisetin in a mice model of oxaliplatin-induced neuropathic pain. Fisetin (1-4 mg/kg, i.p.) did not significantly alter the mechanical hyper...

  4. The evidence for pharmacological treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Sindrup, Søren Hein; Jensen, Troels Staehelin

    2010-01-01

    to compare the efficacy and safety of different treatments for a number of neuropathic pain conditions. One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes......Randomized, double-blind, placebo-controlled trials on neuropathic pain treatment are accumulating, so an updated review of the available evidence is needed. Studies were identified using MEDLINE and EMBASE searches. Numbers needed to treat (NNT) and numbers needed to harm (NNH) values were used......) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids...

  5. Emg Signal Analysis of Healthy and Neuropathic Individuals

    Science.gov (United States)

    Gupta, Ashutosh; Sayed, Tabassum; Garg, Ridhi; Shreyam, Richa

    2017-08-01

    Electromyography is a method to evaluate levels of muscle activity. When a muscle contracts, an action potential is generated and this circulates along the muscular fibers. In electromyography, electrodes are connected to the skin and the electrical activity of muscles is measured and graph is plotted. The surface EMG signals picked up during the muscular activity are interfaced with a system. The EMG signals from individual suffering from Neuropathy and healthy individual, so obtained, are processed and analyzed using signal processing techniques. This project includes the investigation and interpretation of EMG signals of healthy and Neuropathic individuals using MATLAB. The prospective use of this study is in developing the prosthetic device for the people with Neuropathic disability.

  6. Complex Regional Pain Syndrome (CRPS/RSD and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

    Directory of Open Access Journals (Sweden)

    Jennifer Yanow

    2008-01-01

    Full Text Available Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.

  7. ANALGESIC EFFECT OF INTRATHECAL BACLOFEN BOLUS ON NEUROPATHIC PAIN IN SPINAL CORD INJURY PATIENTS.

    Science.gov (United States)

    Kumru, Hatice; Benito-Penalva, Jesus; Kofler, Markus; Vidal, Joan

    2018-05-18

    GABA-ergic neurons are widely distributed throughout the central nervous system, including the spinal cord which is important for the transmission of pain impulses to the brain. Here we hypothesized that intrathecal baclofen (ITB) which is a GABA analogue might exert analgesic effects on neuropathic pain, which could be related to subtypes of pain in spinal cord injury (SCI). SCI patients with a cervical or thoracic lesion and neuropathic pain were randomized to receive either a single ITB bolus or placebo. Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory (NPSI), and Brief Pain Inventory (BPI) were obtained for assessment of neuropathic pain. Spasticity was assessed using Modified Ashworth Scale and visual analogue scale. Evaluations were performed at baseline, and 4, 8, and 24 hours after application of ITB or placebo. Eight patients received ITB, 5 placebo. Neuropathic pain improved significantly in the ITB group based on NRS, BPI, and NPSI, which revealed an effect on all subtypes of pain. Spasticity declined significantly. In the placebo group, there was neither significant change in pain nor in spasticity. An ITB bolus exerted a significant analgesic effect on all subtypes of neuropathic pain in SCI patients. ITB has analgesic effects on all subtypes of neuropathic pain and can improve interference of neuropathic pain with activities of daily living. ITB might be a promising analgesic treatment to control neuropathic pain. Copyright © 2018. Published by Elsevier Inc.

  8. Irrational drug use in neuropathic pain treatment: a twoyear data ...

    African Journals Online (AJOL)

    Irrational drug use in neuropathic pain treatment: a twoyear data analysis. E Tan, A Akıncı, G Ayvaz, T Erbaş, M Ertaş, O Güç, S Hepgüler, S Kiraz, SZ Oşar, S Öztürk, NS Özyalçın, S Palaoğlu, M Uyar, S Ünal, S Yalçın ...

  9. Spinal SIRT1 activation attenuates neuropathic pain in mice.

    Directory of Open Access Journals (Sweden)

    Haijun Shao

    Full Text Available Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1, a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM and nicotinamide adenine dinucleotide (NAD in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.

  10. Activated microglia in the spinal cord underlies diabetic neuropathic pain.

    Science.gov (United States)

    Wang, Dongmei; Couture, Réjean; Hong, Yanguo

    2014-04-05

    Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Spinal interleukin-10 therapy to treat peripheral neuropathic pain.

    Science.gov (United States)

    Milligan, Erin D; Penzkover, Kathryn R; Soderquist, Ryan G; Mahoney, Melissa J

    2012-01-01

      Current research indicates that chronic peripheral neuropathic pain includes a role for glia and the actions of proinflammatory factors. This review briefly discusses the glial and cytokine responses that occur following peripheral nerve damage in support of utilizing anti-inflammatory cytokine interleukin-10 (IL-10) therapy to suppress chronic peripheral neuropathic pain. SPINAL NONVIRAL INTERLEUKIN-10 GENE THERAPY:  IL-10 is one of the most powerful endogenous counter-regulators of proinflammatory cytokine function that acts in the nervous system. Subarachnoid (intrathecal) spinal injection of the gene encoding IL-10 delivered by nonviral vectors has several advantages over virally mediated gene transfer methods and leads to profound pain relief in several animal models. NONVIRAL GENE DELIVERY:  Lastly, data are reviewed that nonviral deoxyribonucleic acid (DNA) encapsulated by a biologically safe copolymer, poly(lactic-co-glycolic) acid (PLGA), thought to protect DNA, leads to significantly improved therapeutic gene transfer in animal models, which additionally and significantly extends pain relief.   The impact of these early studies exploring anti-inflammatory genes emphasizes the exceptional therapeutic potential of new biocompatible intrathecal nonviral gene delivery approaches such as PLGA microparticles. Ultimately, ongoing expression of therapeutic genes is a viable option to treat chronic neuropathic pain in the clinic. © 2012 International Neuromodulation Society.

  12. Neuropathic Pain Following Spinal Cord Injury: Mechanism, Assessment and Treatment

    Directory of Open Access Journals (Sweden)

    Gul Mete Civelek

    2016-04-01

    Full Text Available Spinal cord injury (SCI is a devastating disease which may cause physical, psychological and social dysfunction. Neuropathic pain (NP after SCI is common, can be seen in varying degrees and is one of the most difficultly treated problems developing after SCI. With the addition of the NP to loss of function after SCI, sleep patterns, moods and daily activities of patients are adversely affected. In order to treat pain effectively, classification of pain after SCI must be done carefully and correctly. According to classification of International Pain Study Group, pain after SCI is divided into two main groups as nociceptive and neuropathic pain. Neuropathic pain is defined as %u201Cpain occuring as a direct result of a disease or lesion directly affecting somato-sensorial system%u201D. NP after SCI can be classified according to anatomical region (above the level of lesion, at the level of lesion, below the level of lesion. Treatment of NP after SCI is often challenging and receiving response to treatment may take long time. Therefore, treatment of NP after SCI should be multifactorial. Treatment options include pharmochologic treatment, application of transcutanous electrical nerve stimulation, psychiatric treatment approaches, and surgical approaches in selected cases. In pharmachologic treatment, first line agents are tricyclic antidepresants, pregabalin and gabapentin. In this review, mechanisms and assessment and treatment of NP after SCI is discussed with the guide of current literature.

  13. Assessment of economic effectiveness in treatment of neuropathic pain and refractory angina pectoris using spinal cord stimulation.

    Science.gov (United States)

    Harat, Aleksandra; Sokal, Paweł; Zieliński, Piotr; Harat, Marek; Rusicka, Teresa; Herbowski, Leszek

    2012-01-01

    pectoris and neuropathic pain are lower when using spinal cord stimulation. In the case of refractory angina pectoris, savings reached 46% whereas in the case of neuropathic pain, 13.2%. The costs of the purchase of the device returned in three years for angina pectoris and seven years for neuropathic pain. SCS in both cases brought a reduction of the level of pain and an improvement to quality of life. SCS in both neuropathic pain and refractory angina pectoris is a procedure that brings benefits in the form of savings. After using SCS in both cases, the quality of life improved and the level of pain was reduced.

  14. Suppression of Pax2 attenuates allodynia and hyperalgesia through ET-1-ETAR-NFAT5 signaling in a rat model of neuropathic pain.

    Science.gov (United States)

    Tai, Lydia Wai; Pan, Zhiqiang; Sun, Liting; Li, Haobo; Gu, Pan; Wong, Stanley Sau Ching; Chung, Sookja K; Cheung, Chi Wai

    2018-05-27

    Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, may regulate ET-1. Therefore, we hypothesized that ET-1 axis may be regulated by Pax2 or NFAT5 in the development of neuropathic pain. After partial sciatic nerve ligation (pSNL), rats displayed allodynia and hyperalgesia, which was associated with increased mRNA and protein expressions of spinal Pax2, NFAT5, and mRNA levels of ET-1 and ETAR, but not ETBR. Knockdown of Pax2 or NFAT5 with siRNA, or inhibition of ETAR with BQ-123 attenuated pSNL-induced pain-like behaviors. At molecular level, Pax2 siRNA, but not NFAT5 siRNA, downregulated ET-1 and ETAR, while ETAR inhibitor reduced NFAT5, indicating Pax2 in the upstream of ET-1 axis with NFAT5 in the downstream. Further, suppression of Pax2 (inhibiting ET-1) or impairment of ET-1 signaling (inhibition of ETAR and/or decrease of NFAT5) deactivated mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, supporting the significance of functional regulation of ET-1 axis in neuropathic pain signaling. These findings demonstrate that Pax2 targeting ET-1-ETAR-NFAT5 is a novel regulatory mechanism underlying neuropathic pain. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

    Directory of Open Access Journals (Sweden)

    Jenkins TM

    2012-07-01

    Full Text Available Tim M Jenkins, Trevor S Smart, Frances Hackman, Carol Cooke, Keith KC TanClinical Research, Pfizer Worldwide Research and Development, Sandwich, Kent, UKBackground: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population.Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study.Results: Twenty-five adults (20–70 years of age with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1 pregabalin followed by placebo or (2 placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15. In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015.Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.Keywords: pregabalin, post-traumatic peripheral neuropathic pain, randomized

  16. Allergic Inflammation Leads to Neuropathic Pain via Glial Cell Activation.

    Science.gov (United States)

    Yamasaki, Ryo; Fujii, Takayuki; Wang, Bing; Masaki, Katsuhisa; Kido, Mizuho A; Yoshida, Mari; Matsushita, Takuya; Kira, Jun-Ichi

    2016-11-23

    Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system. We found that mice with asthma, atopic dermatitis, or atopic diathesis had widespread and significantly more activated microglia and astroglia in the spinal cord than those without atopy, and displayed tactile allodynia. Microarray analysis of isolated microglia revealed a dysregulated phenotype showing upregulation of M1 macrophage markers and downregulation of M2 markers in atopic mice. Among the cell surface protein genes, endothelin receptor type B (EDNRB) was most upregulated. Immunohistochemical analysis revealed that EDNRB expression was enhanced in microglia and astroglia, whereas endothelin-1, an EDNRB ligand, was increased in serum, lungs, and epidermis of atopic mice. No EDNRA expression was found in the spinal cord. Expression of FBJ murine osteosarcoma viral oncogene homolog B was significantly higher in the dorsal horn neurons of asthma mice than nonatopic mice. The EDNRB antagonist BQ788 abolished glial and neural activation and allodynia. We found increased serum endothelin-1 in atopic patients with myelitis and neuropathic pain, and activation of spinal microglia and astroglia with EDNRB upregulation in an autopsied case. These results suggest that allergic inflammation induces diffuse glial activation, influencing the nociceptive system via the EDNRB pathway. The prevalence of allergic disorders has markedly increased over the past few decades. Allergic disorders are associated with neuropsychiatric conditions; however, the relationship between allergic inflammation

  17. Diagnosis and medical treatment of neuropathic pain in leprosy.

    Science.gov (United States)

    Arco, Rogerio Del; Nardi, Susilene Maria Tonelli; Bassi, Thiago Gasperini; Paschoal, Vania Del Arco

    2016-08-08

    to identify the difficulties in diagnosing and treating neuropathic pain caused by leprosy and to understand the main characteristics of this situation. 85 patients were treated in outpatient units with reference to leprosy and the accompanying pain. We used a questionnaire known as the Douleur Neuropathic 4 test and we conducted detailed neurological exams. As a result, 42 patients were excluded from the study for not having proved their pain. Out of the 37 patients that experienced pain, 22 (59.5%) had neuropathic pain (or a mixture of this pain and their existing pain) and of these 90.8% considered this pain to be moderate or severe. 81.8% of the sample suffered with this pain for more than 6 months. Only 12 (54.5%) of the patients had been diagnosed with neuropathic pain and in almost half of these cases, this pain had not been diagnosed. With reference to medical treatment (n=12) for neuropathic pain, 5 (41.6%) responded that they became better. For the other 7 (58.4%) there were no changes in relation to the pain or in some cases the pain worsened in comparison to their previous state. Statistical analysis comparing improvements in relation to the pain amongst the patients that were treated (n=12) and those that were not, showed significant differences (value p=0.020). we noted difficulties in diagnosing neuropathic pain for leprosy in that almost half of the patients that were studied had not had their pain diagnosed. We attributed this to some factors such as the non-adoption of the appropriate protocols which led to inadequate diagnosis and treatment that overlooked the true picture. identificar as dificuldades em diagnosticar e tratar a dor neuropática causada pela hanseníase, bem como determinar as características principais dessa situação. examinaram-se 85 pacientes tratados no ambulatório de referência para hanseníase e referiam dor. Aplicou-se questionário, o teste Douleur Neuropathic 4, e criterioso exame neurológico pelo qual exclu

  18. Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models.

    Science.gov (United States)

    Teodoro, Fernanda C; Tronco Júnior, Marcos F; Zampronio, Aleksander R; Martini, Alessandra C; Rae, Giles A; Chichorro, Juliana G

    2013-06-01

    There is accumulating evidence that substance P released from peripheral sensory neurons participates in inflammatory and neuropathic pain. In this study it was investigated the ability of substance P to induce orofacial nociception and thermal and mechanical hyperalgesia, as well as the role of NK1 receptors on models of orofacial inflammatory and neuropathic pain. Substance P injected into the upper lip at 1, 10 and 100 μg/50 μL failed to induce nociceptive behavior. Also, substance P (0.1-10 μg/50 μL) injected into the upper lip did not evoke orofacial cold hyperalgesia and when injected at 1 μg/50 μL did not induce mechanical hyperalgesia. However, substance P at this latter dose induced orofacial heat hyperalgesia, which was reduced by the pre-treatment of rats with a non-peptide NK1 receptor antagonist (SR140333B, 3mg/kg). Systemic treatment with SR140333B (3 mg/kg) also reduced carrageenan-induced heat hyperalgesia, but did not exert any influence on carrageenan-induced cold hyperalgesia. Blockade of NK1 receptors with SR140333B also reduced by about 50% both phases of the formalin response evaluated in the orofacial region. Moreover, heat, but not cold or mechanical, hyperalgesia induced by constriction of the infraorbital nerve, a model of trigeminal neuropathic pain, was abolished by pretreatment with SR140333B. Considering that substance P was peripherally injected (i.e. upper lip) and the NK1 antagonist used lacks the ability to cross the blood-brain-barrier, our results demonstrate that the peripheral SP/NK1 system participates in the heat hyperalgesia associated with inflammation or nerve injury and in the persistent pain evoked by formalin in the orofacial region. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Specific brain morphometric changes in spinal cord injury with and without neuropathic pain

    Directory of Open Access Journals (Sweden)

    Tom B. Mole

    2014-01-01

    Full Text Available Why only certain patients develop debilitating pain after spinal chord injury and whether structural brain changes are implicated remain unknown. The aim of this study was to determine if patients with chronic, neuropathic below-level pain have specific cerebral changes compared to those who remain pain-free. Voxel-based morphometry of high resolution, T1-weighted images was performed on three subject groups comprising patients with pain (SCI-P, n = 18, patients without pain (SCI-N, n = 12 and age- and sex-matched controls (n = 18. The SCI-P group was first compared directly with the SCI-N group and then subsequently with controls. Overall, grey and white matter changes dependent on the presence of pain were revealed. Significant changes were found within the somatosensory cortex and also in corticospinal tracts and visual-processing areas. When the SCI-P group was directly compared with the SCI-N group, reduced grey matter volume was found in the deafferented leg area of the somatosensory cortex bilaterally. This region negatively correlated with pain intensity. Relative to controls, grey matter in this paracentral primary sensory cortex was decreased in SCI-P but conversely increased in SCI-N. When compared with controls, discrepant corticospinal tract white matter reductions were found in SCI-P and in SCI-N. In the visual cortex, SCI-N showed increased grey matter, whilst the SCI-N showed reduced white matter. In conclusion, structural changes in SCI are related to the presence and degree of below-level pain and involve but are not limited to the sensorimotor cortices. Pain-related structural plasticity may hold clinical implications for the prevention and management of refractory neuropathic pain.

  20. Specific brain morphometric changes in spinal cord injury with and without neuropathic pain.

    Science.gov (United States)

    Mole, Tom B; MacIver, Kate; Sluming, Vanessa; Ridgway, Gerard R; Nurmikko, Turo J

    2014-01-01

    Why only certain patients develop debilitating pain after spinal chord injury and whether structural brain changes are implicated remain unknown. The aim of this study was to determine if patients with chronic, neuropathic below-level pain have specific cerebral changes compared to those who remain pain-free. Voxel-based morphometry of high resolution, T1-weighted images was performed on three subject groups comprising patients with pain (SCI-P, n = 18), patients without pain (SCI-N, n = 12) and age- and sex-matched controls (n = 18). The SCI-P group was first compared directly with the SCI-N group and then subsequently with controls. Overall, grey and white matter changes dependent on the presence of pain were revealed. Significant changes were found within the somatosensory cortex and also in corticospinal tracts and visual-processing areas. When the SCI-P group was directly compared with the SCI-N group, reduced grey matter volume was found in the deafferented leg area of the somatosensory cortex bilaterally. This region negatively correlated with pain intensity. Relative to controls, grey matter in this paracentral primary sensory cortex was decreased in SCI-P but conversely increased in SCI-N. When compared with controls, discrepant corticospinal tract white matter reductions were found in SCI-P and in SCI-N. In the visual cortex, SCI-N showed increased grey matter, whilst the SCI-N showed reduced white matter. In conclusion, structural changes in SCI are related to the presence and degree of below-level pain and involve but are not limited to the sensorimotor cortices. Pain-related structural plasticity may hold clinical implications for the prevention and management of refractory neuropathic pain.

  1. Diagnosis of Neuropathic Components in Patients with Back Pain Before and After Surgery.

    Science.gov (United States)

    Lee, Y-J; Koch, E M W; Breidebach, J B; Bornemann, R; Wirtz, D C; Pflugmacher, R

    2016-12-01

    was not excluded. In contrast, in group 2 it was presumed (> 90 %) in 43 % of patients and in 30 % of patients it could not be excluded. Patients with vertebral compression fracture had greater pain intensity (VAS 71) than patients from group 2 (VAS 53). There was no difference in the total score of the Oswestry questionnaire between the two groups (56 % vs. 58 %). Pain intensity was significantly reduced in both groups after the operations. Six months postoperatively, pain intensity (median ordinal scale 0 to 10; acute, maximum, average) was 2, 5, 3 in group 1 and 2, 4, 2 in group 2. Moreover, the final scores of the painDetect questionnaires were significantly lower in both groups after the operations (4 in both groups). The median score of the ODI was reduced in both groups, with an effect size of 0.6. 98 % of the patients in group 1 and 94 % in group 2 were satisfied with the outcome of the operation. Conclusion: The preoperative pain characteristics of patients with vertebral compression fracture is different from those of patients with herniated disc or with spinal cord compression. 43 % of patients in group 2 exhibited a neuropathic pain component and in 30 % this could not be excluded. In contrast, in group 1 only 3 % of the patients exhibited a neuropathic pain component. Postoperatively, pain symptoms were significant reduced in both groups, so that the risk of chronic pain was considerably less. Georg Thieme Verlag KG Stuttgart · New York.

  2. The inhibition of nitric oxide-activated poly(ADP-ribose) synthetase attenuates transsynaptic alteration of spinal cord dorsal horn neurons and neuropathic pain in the rat.

    Science.gov (United States)

    Mao, J; Price, D D; Zhu, J; Lu, J; Mayer, D J

    1997-09-01

    Transsynaptic alteration of spinal cord dorsal horn neurons characterized by hyperchromatosis of cytoplasm and nucleoplasm (so-called 'dark' neurons) occurs in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the common sciatic nerve. The incidence of dark neurons in CCI rats has been proposed to be mediated by glutamate-induced neurotoxicity. In the present study, we examined whether the inhibition of the nitric oxide (NO)-activated poly(ADP-ribose) synthetase (PARS), a nuclear enzyme critical to glutamate-induced neurotoxicity, would both reduce the incidence of dark neurons and attenuate behavioral manifestations of neuropathic pain in CCI rats. Dark neurons were observed bilaterally (with ipsilateral predominance) within the spinal cord dorsal horn, particularly in laminae I-II, of rats 8 days after unilateral sciatic nerve ligation as compared to sham operated rats. The number of dark neurons in the dorsal horn was dose-dependently reduced in CCI rats receiving once daily intrathecal (i.t.) treatment with the PARS inhibitor benzamide (200 or 400 nmol, but not 100 nmol benzamide or saline) for 7 days. Consistent with the histological improvement, thermal hyperalgesia, mechanical hyperalgesia, and low threshold mechano-allodynia also were reliably reduced in CCI rats treated with either 200 or 400 nmol benzamide. Neither dark neurons nor neuropathic pain behaviors were reliably affected by i.t. administration of either 800 nmol novobiocin (a mono(ADP-ribose) synthetase) or 800 nmol benzoic acid (the backbone structure of benzamide), indicating a selective effect of benzamide. Intrathecal treatment with an NO synthase inhibitor NG-nitro-L-arginine methyl ester (40 nmol, but not its inactive D-isomer) utilizing the same benzamide treatment regimen resulted in similar reductions of both dark neurons and neuropathic pain behaviors in CCI rats. These results provide, for the first time, in vivo evidence indicating that benzamide is

  3. Ethanolic extract of Aloe vera ameliorates sciatic nerve ligation induced neuropathic pain

    Directory of Open Access Journals (Sweden)

    Swetha Kanyadhara

    2014-01-01

    Conclusion: The results of the present study validate the use of EEAV to treat neuropathic pain. This effect may be attributed to the decreased migration of neutrophils and due to the anti-oxidant properties of A. vera. Further studies to confirm the mechanism of action will help develop suitable A. vera formulations for neuropathic pain therapy .

  4. Citalopram, venlafaxine and mirtazapine judged on their merits. Treatment of neuropathic pain

    NARCIS (Netherlands)

    Jurg, R.; Van Roon, E.; Koning, H.; Bruinen, T.

    2002-01-01

    The response of neuropathic pain on treatment with elassie analgesics is limited. As primary or adjuvant therapy treatment with tricyclic antidepressants and anti-epileptics can be iniated. Reports on the efficacy of newer antidepressant for neuropathic pain led to evaluation of the study results

  5. Treatment of Chronic Refractory Neuropathic Pelvic Pain with High-Frequency 10-kilohertz Spinal Cord Stimulation.

    Science.gov (United States)

    Simopoulos, Thomas; Yong, Robert J; Gill, Jatinder S

    2017-11-06

    Chronic neuropathic pelvic pain remains a recalcitrant problem in the field of pain management. Case series on application of 10 kHz spinal cord stimulation is presented. High frequency stimulation can improve chronic neuropathic pain states that are known to be mediated at the conus medullaris and offers another avenue for the treatment of these patients. © 2017 World Institute of Pain.

  6. Percutaneous Nerve Stimulation in Chronic Neuropathic Pain Patients due to Spinal Cord Injury: A Pilot Study

    NARCIS (Netherlands)

    Kopsky, D.J.; Ettema, F.W.L.; van der Leeden, M.; Dekker, J.; Stolwijk-Swuste, J.M.

    2014-01-01

    Background: The long-term prognosis for neuropathic pain resolution following spinal cord injury (SCI) is often poor. In many SCI patients, neuropathic pain continues or even worsens over time. Thus, new treatment approaches are needed. We conducted a pilot study to evaluate the feasibility and

  7. Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain.

    Science.gov (United States)

    Lim, Eun Yeong; Kim, Yun Tai

    2016-01-01

    Neuropathic pain, defined as pain caused by a lesion or disease of the somatosensory nervous system, is characterized by dysesthesia, hyperalgesia, and allodynia. The number of patients with this type of pain has increased rapidly in recent years. Yet, available neuropathic pain medicines have undesired side effects, such as tolerance and physical dependence, and do not fully alleviate the pain. The mechanisms of neuropathic pain are still not fully understood. Injury causes inflammation and immune responses and changed expression and activity of receptors and ion channels in peripheral nerve terminals. Additionally, neuroinflammation is a known factor in the development and maintenance of neuropathic pain. During neuropathic pain development, the C-C motif chemokine receptor 2 (CCR2) acts as an important signaling mediator. Traditional plant treatments have been used throughout the world for treating diseases. We and others have identified food-derived compounds that alleviate neuropathic pain. Here, we review the natural compounds for neuropathic pain relief, their mechanisms of action, and the potential benefits of natural compounds with antagonistic effects on GPCRs, especially those containing CCR2, for neuropathic pain treatment.

  8. Effect of Xylopic Acid on Paclitaxel-induced Neuropathic pain in rats ...

    African Journals Online (AJOL)

    Xylopic acid, a diterpenoid isolated from the fruits of Xylopia aethiopica has demonstrated analge-sic properties in acute pain models. It was therefore evaluated for its analgesic properties in paclitaxel-induced neuropathic pain, a type of pain difficult to treat clinically. Neuropathic pain was induced in rats by injecting 2 mg ...

  9. Gabapentin for chronic neuropathic pain and fibromyalgia in adults.

    Science.gov (United States)

    Moore, R Andrew; Wiffen, Philip J; Derry, Sheena; Toelle, Thomas; Rice, Andrew S C

    2014-04-27

    This review is an update of a review published in 2011, itself a major update of previous reviews published in 2005 and 2000, investigating the effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage chronic neuropathic pain and fibromyalgia. To assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain and fibromyalgia. We identified randomised trials of gabapentin for chronic neuropathic pain or fibromyalgia by searching the databases MEDLINE (1966 to March 2014), EMBASE (1980 to 2014 week 10), and CENTRAL in The Cochrane Library (Issue 3 of 12, 2014). We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources, and searched Clinicaltrials.gov. Searches were run originally in 2011 and the date of the most recent search was 17 March 2014. Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain or fibromyalgia with assessment of pain intensity, pain relief, or both, using validated scales. Participants were adults. Three review authors independently extracted efficacy and adverse event data, examined issues of study quality, and assessed risk of bias. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.For efficacy, we calculated the number needed

  10. Neuropathic pain, depressive symptoms, and C-reactive protein in sciatica patients.

    Science.gov (United States)

    Uher, Tomas; Bob, Petr

    2013-03-01

    There is evidence that neuropathic pain component in low back pain (LBP) patients is associated with higher ratings of comorbidities such as depression and anxiety disorders. In line with current findings, the purpose of this clinical study is to examine a hypothesis regarding a relationship of neuropathic pain component, depression, and other psychopathological symptoms in a specific group of LBP patients with sciatica pain. With respect to findings that depression is related to inflammatory changes, and inflammatory mediators may play a role in neuropathic pain generation, we have assessed also serum C-reactive protein (CRP). Results of the present study show that increased neuropathic pain component in sciatica patients is associated with elevated levels of depression, anxiety, alexithymia, and serum CRP levels. In conclusion, results of this study indicate that CRP levels in sciatica patients are closely associated with neuropathic pain.

  11. Slack channels expressed in sensory neurons control neuropathic pain in mice.

    Science.gov (United States)

    Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

    2015-01-21

    Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

  12. Neuropathic diabetic foot ulcers – evidence-to-practice

    Directory of Open Access Journals (Sweden)

    Ndip A

    2012-02-01

    Full Text Available Agbor Ndip1–3, Leonard Ebah3,4, Aloysius Mbako51Department of Diabetes and Medicine, Manchester Royal Infirmary, Central Manchester Foundation Trust, UK; 2Department of Medicine, Royal Bolton Hospital, Bolton, UK; 3Cardiovascular Research Group, School of Biomedicine, University of Manchester, UK; 4Department of Renal Medicine, Manchester Royal Infirmary, Central Manchester Foundation Trust, UK; 5Department of Orthopaedic Surgery, Wrexham Maelor Hospital, Wales, UKAbstract: Foot ulcers and their attendant complications are disquietingly high in people with diabetes, a majority of whom have underlying neuropathy. This review examines the evidence base underpinning the prevention and management of neuropathic diabetic foot ulcers in order to inform best clinical practice. Since it may be impractical to ask patients not to weight-bear at all, relief of pressure through the use of offloading casting devices remains the mainstay for management of neuropathic ulcers, whilst provision of appropriate footwear is essential in ulcer prevention. Simple non-surgical debridement and application of hydrogels are both effective in preparing the wound bed for healthy granulation and therefore enhancing healing. Initial empirical antibiotic therapy for infected ulcers should cover the most common bacterial flora. There is limited evidence supporting the use of adjunctive therapies such as hyperbaric oxygen and cytokines or growth factors. In selected cases, recombinant human platelet-derived growth factor has been shown to enhance healing; however, its widespread use cannot be advised due to the availability of more cost-effective approaches. While patient education may be beneficial, the evidence base remains thin and conflicting. In conclusion, best management of foot ulcers is achieved by what is taken out of the foot (pressure, callus, infection, and slough rather than what is put on the foot (adjuvant treatment.Keywords: diabetic foot ulcers, neuropathic

  13. Pharmacological evaluation of tacrolimus (FK-506 on ischemia reperfusion induced vasculatic neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    Sood Shailja

    2010-06-01

    Full Text Available Abstract Background Ischemia reperfusion (I/R is common in various pathological conditions like diabetic complication, rheumatic arthritis, necrotizing vascular occlusive disease and trauma. Methods We have evaluated the effect of tacrolimus (1, 2 and 3 mg/kg, p.o. for 10 consecutive days on femoral arterial ischemic reperfusion (I/R induced neuropathic pain in rats. Behavioral parameters (i.e. hot plate, radiant heat, acetone drop, tail heat hyperalgesia, tail flick and tail cold allodynia tests were assessed at different time intervals (i.e. 0, 1, 4, 7, 10, 13 and 16th day and biochemical analysis in serum and tissue samples were also performed along with histopathological studies. Results Behavioral pain assessment revealed increase in the paw and tail withdrawal threshold in tacrolimus treated groups against hyperalgesic and allodynic stimuli as compared to the sham control group. We observed a decrease in the serum nitrate and thiobarbituric acid reactive substance (TBARS levels along with reduction in tissue myeloperoxidase (MPO and total calcium levels, whereas, rise in tissue reduced glutathione levels in tacrolimus treated groups. However, significant results were obtained in medium and high dose treated group as compared to sham control group. Histopathological study had revealed the increase in the neuronal edema and axonal degeneration in the I/R group whereas, tacrolimus ameliorate these effects. Conclusion Our results indicate the anti-oxidative, anti-inflammatory and calcium modulatory actions of tacrolimus. Therefore, it can be used as a therapeutic agent for the treatment of vascular inflammatory related neuropathic pain.

  14. Stratifying patients with peripheral neuropathic pain based on sensory profiles

    DEFF Research Database (Denmark)

    Vollert, Jan; Maier, Christoph; Attal, Nadine

    2017-01-01

    In a recent cluster analysis, it has been shown that patients with peripheral neuropathic pain can be grouped into 3 sensory phenotypes based on quantitative sensory testing profiles, which are mainly characterized by either sensory loss, intact sensory function and mild thermal hyperalgesia and...... populations that need to be screened to reach a subpopulation large enough to conduct a phenotype-stratified study. The most common phenotype in diabetic polyneuropathy was sensory loss (83%), followed by mechanical hyperalgesia (75%) and thermal hyperalgesia (34%, note that percentages are overlapping...

  15. Ketamine Does Not Produce Relief of Neuropathic Pain in Mice Lacking the β-Common Receptor (CD131)

    Science.gov (United States)

    Swartjes, Maarten; Niesters, Marieke; Heij, Lara; Dunne, Ann; Aarts, Leon; Hand, Carla Cerami; Kim, Hyung-Suk; Brines, Michael; Cerami, Anthony; Dahan, Albert

    2013-01-01

    Neuropathic pain (NP) is a debilitating condition associated with traumatic, metabolic, autoimmune and neurological etiologies. Although the triggers for NP are diverse, there are common underlying pathways, including activation of immune cells in the spinal cord and up-regulation of the N-methyl-D-aspartate receptor (NMDAR). Ketamine, a well-known NDMAR antagonist, reduces neuropathic pain in a sustained manner. Recent study has shown that the novel 11-amino acid peptide erythropoietin derivative ARA290 produces a similar, long-lasting relief of NP. Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP. Although the effects of ketamine and ARA 290 on NP and its molecular mediators suggest a common mechanism of action, ARA 290 has no affinity for the NMDAR and acts specifically via the innate repair receptor (IRR) involved in tissue protection. We speculated therefore, that the IRR might be critically involved in the action of ketamine on neuropathic pain. To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR. Ketamine (50 mg/kg) and ARA 290 (30 µg/kg) produced divergent effects on acute pain: ketamine produced profound antinociception accompanied with psychomotor side effects, but ARA290 did not, in both normal and knock out mice. In contrast, while both drugs were antiallodynic in WT mice, they had no effect on NP in mice lacking the βcR. Together, these results show that an intact IRR is required for the effective treatment of NP with either ketamine or ARA 290, but is not involved in ketamine’s analgesic and side effects. PMID:23936499

  16. Altering Conventional to High Density Spinal Cord Stimulation: An Energy Dose-Response Relationship in Neuropathic Pain Therapy.

    Science.gov (United States)

    Wille, Frank; Breel, Jennifer S; Bakker, Eric W P; Hollmann, Markus W

    2017-01-01

    To examine whether converting from conventional Spinal Cord Stimulation (SCS) to High Density (HD) SCS reduces neuropathic pain over a period of 12 months in patients with failed SCS therapy. Retrospective, open label, single center, consecutive case series of 30 neuropathic pain patients (Failed Back Surgery Syndrome [FBSS], Complex Regional Pain Syndrome [CRPS], and polyneuropathy [NP]). Patients with an initial adequate response to conventional SCS, but in whom pain increased over time, were included (Numeric Rating Scales [NRS] >6). These patients were stimulated with HD-SCS parameters and followed-up for 12 months. We report pain intensity, measured with NRS, before SCS implantation, 1 and 3 months after starting SCS with conventional stimulation, and after 1, 6, and 12 months of HD SCS. Pain reduction with conventional stimulation was initially adequate (NRS mean 8.6 to 5.3 at three months postimplant) but increased over time to a mean NRS of 7.7 at the time of reprogramming. NRS scores decreased significantly to 4.3 (p = 0.015) after reprogramming from conventional SCS (30 Hz, 300 µsec, 3.0 V) to HD SCS (409 Hz, range 130-1000 Hz, 409 µsec, 2.4V) in the patients still using HD-SCS at 12 months. In the nonresponders (patients who stopped HD-SCS for any reason), 76% had a diagnosis of FBSS. Almost half of the patients aborting HD-SCS preferred to feel paresthesias despite better pain relief. There was a significant difference between nonresponders and responders regarding the amount of electrical energy delivered to the spinal cord. Neuropathic pain suppression is significantly enhanced after converting from failed conventional SCS to HD SCS in patients with FBSS, CRPS, and NP over a measured period of 12 months. There appears to be a dose-related response between the amount of energy delivered to the spinal cord and clinical effect. © 2016 International Neuromodulation Society.

  17. Effect of a polyherbal formulation cream on diabetic neuropathic pain among patients with type 2 diabetes – A pilot study

    Science.gov (United States)

    Viswanathan, Vijay; Rajsekar, Seena; Selvaraj, Bamila; Kumpatla, Satyavani

    2016-01-01

    Background & objectives: Painful diabetic neuropathy is a common complication of diabetes and can severely limit patients’ daily functions. The aim of this pilot study was to evaluate the safety and effect of using a polyherbal formulation in reducing the symptoms of diabetic neuropathic pain in comparison with placebo among patients with type 2 diabetes. Methods: A total of 50 (M:F = 33:17) consecutive type 2 diabetes patients with painful diabetic neuropathy were enrolled in this study. All these patients had either two or more symptoms of diabetic neuropathy such as pain, burning and pricking sensations and numbness in their feet. They were randomly assigned to two groups: group 1 (n = 26) patients were treated with polyherbal formulation cream and group 2 (n = 24) patients were administered placebo. The patients were followed up for six months. Changes in the symptoms of painful diabetic neuropathy of each patient were recorded at baseline, third and sixth month using the Diabetic Neuropathic Score. Results: The mean age of the patients, duration of diabetes and glycated haemoglobin (HbA1c) were similar in both groups at baseline. During follow up visits, there was a decrease in the HbA1c levels in the study and control groups. The symptoms of painful diabetic neuropathy were also similar in both groups at baseline. A significant decrease in symptoms of neuropathic pain was observed among the group of patients treated with polyherbal formulation cream (76.9 per cent) compared to the placebo-treated group (12.5 per cent) (P<0.001), at the end of the final follow up. Interpretation & conclusions: In this pilot study polyherbal formulation cream was found to be effective as well as safe to treat painful diabetic neuropathy. However, its long term use needs to be evaluated for any further effectiveness and side effects. PMID:27934800

  18. Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.

    Science.gov (United States)

    Wu, Shao-Wei; Wang, Yi-Chia; Hsieh, Paul-Chen; Tseng, Ming-Tsung; Chiang, Ming-Chang; Chu, Chih-Pang; Feng, Fang-Ping; Lin, Yea-Huey; Hsieh, Sung-Tsang; Chao, Chi-Chao

    2017-03-01

    Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.

  19. Implications and mechanism of action of gabapentin in neuropathic pain.

    Science.gov (United States)

    Kukkar, Ankesh; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2013-03-01

    Gabapentin is an anti-epileptic agent but now it is also recommended as first line agent in neuropathic pain, particularly in diabetic neuropathy and post herpetic neuralgia. α2δ-1, an auxillary subunit of voltage gated calcium channels, has been documented as its main target and its specific binding to this subunit is described to produce different actions responsible for pain attenuation. The binding to α2δ-1 subunits inhibits nerve injury-induced trafficking of α1 pore forming units of calcium channels (particularly N-type) from cytoplasm to plasma membrane (membrane trafficking) of pre-synaptic terminals of dorsal root ganglion (DRG) neurons and dorsal horn neurons. Furthermore, the axoplasmic transport of α2δ-1 subunits from DRG to dorsal horns neurons in the form of anterograde trafficking is also inhibited in response to gabapentin administration. Gabapentin has also been shown to induce modulate other targets including transient receptor potential channels, NMDA receptors, protein kinase C and inflammatory cytokines. It may also act on supra-spinal region to stimulate noradrenaline mediated descending inhibition, which contributes to its anti-hypersensitivity action in neuropathic pain.

  20. Acute neuropathic joint in diabetic foot: Plain radiographic findings

    International Nuclear Information System (INIS)

    Yoon, Dae Young; Kang, Heung Sik; Sim, Jung Suk; Yoon, Yong Kyu; Kim, Chu Wan

    1994-01-01

    To determine the plain film findings of acute neuropathic joint in diabetic foot. Acute neuropathic joint in diabetic foot was considered when fragmentation of the articular ends of bone and subluxation of the affected joint developed within eight weeks after clinical onset of diabetic gangrene. Eight toes of six diabetics were satisfactory to our criteria. We analyzed plain radiographic findings of the affected joint and soft tissue, interval changes in followed-up radiographs, and deformities after healing. The time interval between clinical onset of gangrene and bone destruction ranges from 2 weeks to 4 weeks(mean 2.6 weeks). Plane radiographs showed fragmentation of the articular ends, subluxation, and soft tissue swelling of the metatarsophalangeal joint or interphalangeal joint. The significant feature of these patients was rapid progression of the lesions. Clinically, all patients had diabetic gangrene in affected toes, however, there was no evidence of osteomyelitis in our series. Amputation was done in 2 cases, and lesions in 3 of the remaining 4 cases were repaired spontaneously with regression of gangrene, leaving radiological residua such as pointed-end, tapered-end, and ball and socket deformity. Rapid disorganisation of the joint with associated evidence of soft tissue gangrene in plain radiograph is believed to be valuable for the diagnosis of diabetic osteoarthropathy

  1. Chronic Orofacial Pain: Burning Mouth Syndrome and Other Neuropathic Disorders

    Science.gov (United States)

    Tait, Raymond C; Ferguson, McKenzie; Herndon, Christopher M

    2017-01-01

    Chronic orofacial pain is a symptom associated with a wide range of neuropathic, neurovascular, idiopathic, and myofascial conditions that affect a significant proportion of the population. While the collective impact of the subset of the orofacial pain disorders involving neurogenic and idiopathic mechanisms is substantial, some of these are relatively uncommon. Hence, patients with these disorders can be vulnerable to misdiagnosis, sometimes for years, increasing the symptom burden and delaying effective treatment. This manuscript first reviews the decision tree to be followed in diagnosing any neuropathic pain condition, as well as the levels of evidence needed to make a diagnosis with each of several levels of confidence: definite, probable, or possible. It then examines the clinical literature related to the idiopathic and neurogenic conditions that can occasion chronic orofacial pain, including burning mouth syndrome, trigeminal neuralgia, glossopharyngeal neuralgia, post-herpetic neuralgia, and atypical odontalgia. Temporomandibular disorders also are examined as are other headache conditions, even though they are not neurologic conditions, because they are common and can mimic symptoms of the latter disorders. For each of these conditions, the paper reviews literature regarding incidence and prevalence, physiologic and other contributing factors, diagnostic signs and symptoms, and empirical evidence regarding treatments. Finally, in order to improve the quality and accuracy of clinical diagnosis, as well as the efficiency with which effective treatment is initiated and delivered, criteria are offered that can be instrumental in making a differential diagnosis. PMID:28638895

  2. Interventional management of neuropathic pain: NeuPSIG recommendations

    Science.gov (United States)

    Dworkin, Robert H.; O’Connor, Alec B.; Kent, Joel; Mackey, Sean C.; Raja, Srinivasa N.; Stacey, Brett R.; Levy, Robert M.; Backonja, Miroslav; Baron, Ralf; Harke, Henning; Loeser, John D.; Treede, Rolf-Detlef; Turk, Dennis C.; Wells, Christopher D.

    2015-01-01

    Neuropathic pain (NP) is often refractory to pharmacologic and non-interventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group (NeuPSIG), the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central post-stroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: (1) epidural injections for herpes zoster; (2) steroid injections for radiculopathy; (3) SCS for FBSS; and (4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor RF lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available of data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials; long-term studies; and head-to-head comparisons among different interventional and non-interventional treatments. PMID:23748119

  3. Chronic Orofacial Pain: Burning Mouth Syndrome and Other Neuropathic Disorders.

    Science.gov (United States)

    Tait, Raymond C; Ferguson, McKenzie; Herndon, Christopher M

    2017-03-01

    Chronic orofacial pain is a symptom associated with a wide range of neuropathic, neurovascular, idiopathic, and myofascial conditions that affect a significant proportion of the population. While the collective impact of the subset of the orofacial pain disorders involving neurogenic and idiopathic mechanisms is substantial, some of these are relatively uncommon. Hence, patients with these disorders can be vulnerable to misdiagnosis, sometimes for years, increasing the symptom burden and delaying effective treatment. This manuscript first reviews the decision tree to be followed in diagnosing any neuropathic pain condition, as well as the levels of evidence needed to make a diagnosis with each of several levels of confidence: definite, probable, or possible. It then examines the clinical literature related to the idiopathic and neurogenic conditions that can occasion chronic orofacial pain, including burning mouth syndrome, trigeminal neuralgia, glossopharyngeal neuralgia, post-herpetic neuralgia, and atypical odontalgia. Temporomandibular disorders also are examined as are other headache conditions, even though they are not neurologic conditions, because they are common and can mimic symptoms of the latter disorders. For each of these conditions, the paper reviews literature regarding incidence and prevalence, physiologic and other contributing factors, diagnostic signs and symptoms, and empirical evidence regarding treatments. Finally, in order to improve the quality and accuracy of clinical diagnosis, as well as the efficiency with which effective treatment is initiated and delivered, criteria are offered that can be instrumental in making a differential diagnosis.

  4. Acute neuropathic joint in diabetic foot: Plain radiographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Dae Young; Kang, Heung Sik; Sim, Jung Suk; Yoon, Yong Kyu; Kim, Chu Wan [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1994-05-15

    To determine the plain film findings of acute neuropathic joint in diabetic foot. Acute neuropathic joint in diabetic foot was considered when fragmentation of the articular ends of bone and subluxation of the affected joint developed within eight weeks after clinical onset of diabetic gangrene. Eight toes of six diabetics were satisfactory to our criteria. We analyzed plain radiographic findings of the affected joint and soft tissue, interval changes in followed-up radiographs, and deformities after healing. The time interval between clinical onset of gangrene and bone destruction ranges from 2 weeks to 4 weeks(mean 2.6 weeks). Plane radiographs showed fragmentation of the articular ends, subluxation, and soft tissue swelling of the metatarsophalangeal joint or interphalangeal joint. The significant feature of these patients was rapid progression of the lesions. Clinically, all patients had diabetic gangrene in affected toes, however, there was no evidence of osteomyelitis in our series. Amputation was done in 2 cases, and lesions in 3 of the remaining 4 cases were repaired spontaneously with regression of gangrene, leaving radiological residua such as pointed-end, tapered-end, and ball and socket deformity. Rapid disorganisation of the joint with associated evidence of soft tissue gangrene in plain radiograph is believed to be valuable for the diagnosis of diabetic osteoarthropathy.

  5. Walking with Neuropathic Pain: Paradoxical Shift from Burden to Support?

    Directory of Open Access Journals (Sweden)

    David J. Kopsky

    2015-01-01

    Full Text Available Baclofen 5% cream can be used for the treatment of neuropathic pain. We describe an unusual case of a neuropathic pain patient with spinal cord injury. A 71-year-old woman with a partial spinal cord injury lesion at L4 complained of tingling, pins and needles, and burning in her legs. She scored her pain as 6 before adding baclofen 5% cream to her pain medication (pregabalin 450 mg, acetaminophen 3000 mg, and diclofenac 150 mg daily. One month later she experienced complete pain relief, though experienced increased difficulties in walking, leading to frequent falls. Her steadier walking without stumbling and falling was more important to her than pain reduction. Thus she decided to stop using baclofen. This unusual case report discusses two important issues that relate to pain medicine and rehabilitation in patients with painful spinal cord lesions: (1 the presence of wide areas of sensory loss “covered” by the presence of painful sensations and (2 pathological sensations that can be used and integrated in the body schema to create an improved spatiovisual orientation and thus mobility. Both these aspects have to be taken into account when treating pain and design rehabilitation programs.

  6. Successful spinal cord stimulation for neuropathic below-level spinal cord injury pain following complete paraplegia: a case report.

    Science.gov (United States)

    Reck, Tim A; Landmann, Gunther

    2017-01-01

    Neuropathic pain is common in patients with spinal cord injury (SCI) and often difficult to treat. We report a case where epidural spinal cord stimulation (SCS) below the level of injury has been successfully applied in a patient with a complete spinal cord lesion. A 53-year-old female presented with neuropathic below-level SCI pain of both lower legs and feet due to complete SCI below T5. Time and pain duration since injury was 2 years. Pain intensity was reported on numeric rating scale with an average of 7/10 (0 meaning no pain, 10 meaning the worst imaginable pain), but also with about 8-10 pain attacks during the day with an intensity of 9/10, which lasted between some minutes and half an hour. SCS was applied below the level of injury at-level T11-L1. After a successful 2 weeks testing period the pulse generator has been implanted permanently with a burst-stimulation pattern. The average pain was reduced to a bearable intensity of 4/10, in addition attacks could be reduced both in frequency and in intensity. This effects lasted for at least three months of follow-up. Even in case of complete SCI, SCS might be effective. Mechanisms of pain relief remain unclear. A modulation of suggested residual spinothalamic tract function may play a role. Further investigation has to be carried out to support this theory.

  7. Combined approaches for the relief of spinal cord injury-induced neuropathic pain.

    Science.gov (United States)

    Gwak, Young S; Kim, Hee Young; Lee, Bong Hyo; Yang, Chae Ha

    2016-04-01

    The adequate treatment of spinal cord injury (SCI)-induced neuropathic pain still remains an unresolved problem. The current medications predominantly used in the SCI-induced neuropathic pain therapy are morphine, anticonvulsants, antidepressants, and antiepileptics, which suggests that psychiatric aspects might be important factors in the treatment of neuropathic pain. It is well documented that the modulation of the sensory events is not a unique way for achieving pain relief. In addition, pain patients still express dissatisfaction and complain of unwanted effects of the medications, suggesting that alternative approaches for the treatment of neuropathic pain are essential. In psychiatry, pain relief represents relaxation and a feeling of comfort and satisfaction, which suggests that cognitive and emotional motivations are important factors in the treatment of neuropathic pain. The comorbidity of chronic pain and psychiatric disorders, which is well recognized, suggests that the effective therapeutic relief for neuropathic pain induced by SCI can be achieved in conjunction with the management of the sensory and psychiatric aspects of patient. In this review, we address the feasibility of a combined acupuncture and pharmacotherapy treatment for the relief of neuropathic pain behavior following SCI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Neuropathic Pain and Psychological Morbidity in Patients with Treated Leprosy: A Cross-Sectional Prevalence Study in Mumbai

    Science.gov (United States)

    Lasry-Levy, Estrella; Hietaharju, Aki; Pai, Vivek; Ganapati, Ramaswamy; Rice, Andrew S. C.; Haanpää, Maija; Lockwood, Diana N. J.

    2011-01-01

    Background Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated. Methodology/Principal Findings Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity. Conclusions/Significance One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity. PMID:21408111

  9. Anticonvulsants or Antidepressants in Combination Pharmacotherapy for Treatment of Neuropathic Pain in Cancer Patients: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Guan, Jia; Tanaka, Shiro; Kawakami, Koji

    2016-08-01

    To investigate the efficacy of anticonvulsants or antidepressants in combination pharmacotherapy for treatment of neuropathic pain in cancer patients. We systematically searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the metaRegister of Controlled Trials for randomized controlled trials that compared anticonvulsants or antidepressants in combination pharmacotherapy (experimental group) with treatments without anticonvulsants or antidepressants (control group) for neuropathic pain in cancer patients. Risk of bias was evaluated in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was a mean difference (MD) in change in global pain analyzed by a random-effects model. Eight trials met the inclusion criteria with a total of 1359 participants of whom 698 received an experimental intervention. The MD in change in global pain suggested a favorable association with anticonvulsants or antidepressants in combination pharmacotherapy compared with control groups (MD, -0.41; 95% confidence interval, -0.70 to -0.12) with no heterogeneity across trials (I=0%). The MD in change estimated in all sensitivity analyses ranged from -0.36 to -0.47, suggesting that these effects were consistent across different study designs and statistical assumptions. Anticonvulsants or antidepressants in combination pharmacotherapy reduce neuropathic pain in cancer patients compared with treatments without anticonvulsants or antidepressants. Limited evidence precludes a recommendation on specific adjuvants in combination pharmacotherapy.

  10. Effects of Danggui Sini decoction on neuropathic pain: experimental studies and clinical pharmacological significance of inhibiting glial activation and proinflammatory cytokines in the spinal cord
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    Science.gov (United States)

    Liu, Ming; Qiang, Qiu Hong; Ling, Qian; Yu, Chang Xi; Li, Xuejun; Liu, Suhuan; Yang, Shuyu

    2017-05-01

    Neuropathic pain responds poorly to drug treatments. Partial relief is achieved in only about half of the patients. Danggui Sini decoction (DSD), an aqueous extract of Angelica sinensis, Ramulus Cinnamomi, and Radix Puerariae, has been used extensively in China to treat inflammatory and ischemic diseases. The current study examined the putative effects of DSD on neuropathic pain. We used two commonly-used animal models: chronic constriction injury (CCI) and diabetic neuropathy for the study. And we examined effects of DSD on pain response, activation of microglia and astroglia in spinal dorsal horn, and expression of proinflammatory cytokines in the spinal cord. Consecutive intragastric administration of DSD (25 - 100 mg/kg) for 10 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models, DSD inhibited the over-expression of specific markers for microglia (Iba-1) and astroglia (GFAP) activation in the spinal dorsal horn. DSD also reduced the elevated nuclear NF-κB level and inhibited the up-regulation of proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. DSD can alleviate CCI and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of DSD may be related to the suppression of spinal NF-κB activation and/or cytokines expression.
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  11. Perineural pretreatment of bee venom attenuated the development of allodynia in the spinal nerve ligation injured neuropathic pain model; an experimental study.

    Science.gov (United States)

    Koh, Won Uk; Choi, Seong Soo; Lee, Jong Hyuk; Lee, So Hee; Lee, Sun Kyung; Lee, Yoon Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

    2014-11-04

    Diluted bee venom (BV) is known to have anti-nociceptive and anti-inflammatory effects. We therefore assessed whether perineural bee venom pretreatment could attenuate the development of neuropathic pain in the spinal nerve ligation injured animal model. Neuropathic pain was surgically induced in 30 male Sprague Dawley rats by ligation of the L5 and L6 spinal nerves, with 10 rats each treated with saline and 0.05 and 0.1 mg BV. Behavioral testing for mechanical, cold, and thermal allodynia was conducted on postoperative days 3 to 29. Three rats in each group and 9 sham operated rats were sacrificed on day 9, and the expression of transient receptor potential vanilloid type 1 (TRPV1), ankyrin type 1 (TRPA1), and melastatin type 8 (TRPM8) receptors in the ipsilateral L5 dorsal root ganglion was analyzed. The perineural administration of BV to the spinal nerves attenuated the development of mechanical, thermal, and cold allodynia, and the BV pretreatment reduced the expression of TRPV1, TRPA1, TRPM8 and c - Fos in the ipsilateral dorsal root ganglion. The current study demonstrates that the perineural pretreatment with diluted bee venom before the induction of spinal nerve ligation significantly suppresses the development of neuropathic pain. Furthermore, this bee venom induced suppression was strongly related with the involvement of transient receptor potential family members.

  12. A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients.

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    Anne-Li Lind

    Full Text Available The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF. We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS and neuropathic pain, where patients were treated with spinal cord stimulation (SCS. Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.

  13. GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury.

    Science.gov (United States)

    Falnikar, Aditi; Hala, Tamara J; Poulsen, David J; Lepore, Angelo C

    2016-03-01

    Development of neuropathic pain occurs in a major portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. Following SCI, chronic dysregulation of extracellular glutamate homeostasis has been shown to play a key role in persistent central hyperexcitability of superficial dorsal horn neurons that mediate pain neurotransmission, leading to various forms of neuropathic pain. Astrocytes express the major CNS glutamate transporter, GLT1, which is responsible for the vast majority of functional glutamate uptake, particularly in the spinal cord. In our unilateral cervical contusion model of mouse SCI that is associated with ipsilateral forepaw heat hypersensitivity (a form of chronic at-level neuropathic pain-related behavior), we previously reported significant and long-lasting reductions in GLT1 expression and functional GLT1-mediated glutamate uptake in cervical spinal cord dorsal horn. To therapeutically address GLT1 dysfunction following cervical contusion SCI, we injected an adeno-associated virus type 8 (AAV8)-Gfa2 vector into the superficial dorsal horn to increase GLT1 expression selectively in astrocytes. Compared to both contusion-only animals and injured mice that received AAV8-eGFP control injection, AAV8-GLT1 delivery increased GLT1 protein expression in astrocytes of the injured cervical spinal cord dorsal horn, resulting in a significant and persistent reversal of already-established heat hypersensitivity. Furthermore, AAV8-GLT1 injection significantly reduced expression of the transcription factor and marker of persistently increased neuronal activation, ΔFosB, in superficial dorsal horn neurons. These results demonstrate that focal restoration of GLT1 expression in the superficial dorsal horn is a promising target for treating chronic neuropathic pain following SCI. © 2015 Wiley Periodicals, Inc.

  14. Dexmedetomidine attenuates neuropathic pain in chronic constriction injury by suppressing NR2B, NF-κB, and iNOS activation

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    Feng Liang

    2017-05-01

    Full Text Available The effective treatment of patients suffering from neuropathic pain remains challenging. Dexmedetomidine (DEX possesses anti-inflammatory activity. However, the role of DEX in neuropathic pain is still unclear. The aim of the present study was to examine DEX an α2-adrenoceptor agonist could improve pain hypersensitivity and reduce inflammatory in a chronic constriction injury (CCI model of the sciatic nerve in Sprague-Dawley rats. Dex was intrathecally administrated 1-h after operation. The paw mechanical withdrawal threshold (MWT and paw withdrawal thermal latency (PWTL were measured on day 1 before operation and on days 1, 7, 14 and 21 after operation, respectively. On day 21, all the rats were decapitated to collect the L4-6 segments of the spinal cord to examine IL-1, TNF-α, IL-6, NR2B, NF-κB, and iNOS mRNA levels using RT-PCR. The postoperative MWT and PWTL were significantly decreased in CCI, and DEX groups as compared to those before surgery and Sham group (P < 0.05. And DEX reversed this trend (P < 0.05. Interleukin 1 (IL-1, tumor necrosis factor α (TNF-α, IL-6 mRNA expression significantly increased postsurgery in CCI group as compared to that of Sham group (P < 0.05; DEX blocked increased IL-1, TNF-α, IL-6, N-methyl-D-aspartate (NMDA receptor 2B (NR2B, nuclear factor κB (NF-κB, and inducible isoform of nitric oxide synthase (iNOS mRNA levels (P < 0.05. DEX may alleviate neuropathic hypersensitivity and inflammation partially by inhibiting NR2B, NF-κB, and iNOS expression in the spinal cord of rats with neuropathic pain resulting from CCI of the sciatic nerve.

  15. An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

    2016-01-01

    Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. PMID:27286745

  16. Botulinum Toxin Type A—A Modulator of Spinal Neuron–Glia Interactions under Neuropathic Pain Conditions

    Directory of Open Access Journals (Sweden)

    Ewelina Rojewska

    2018-04-01

    Full Text Available Neuropathic pain represents a significant clinical problem because it is a chronic condition often refractory to available therapy. Therefore, there is still a strong need for new analgesics. Botulinum neurotoxin A (BoNT/A is used to treat a variety of clinical diseases associated with pain. Glia are in continuous bi-directional communication with neurons to direct the formation and refinement of synaptic connectivity. This review addresses the effects of BoNT/A on the relationship between glia and neurons under neuropathic pain. The inhibitory action of BoNT/A on synaptic vesicle fusion that blocks the release of miscellaneous pain-related neurotransmitters is known. However, increasing evidence suggests that the analgesic effect of BoNT/A is mediated through neurons and glial cells, especially microglia. In vitro studies provide evidence that BoNT/A exerts its anti-inflammatory effect by diminishing NF-κB, p38 and ERK1/2 phosphorylation in microglia and directly interacts with Toll-like receptor 2 (TLR2. Furthermore, BoNT/A appears to have no more than a slight effect on astroglia. The full activation of TLR2 in astroglia appears to require the presence of functional TLR4 in microglia, emphasizing the significant interaction between those cell types. In this review, we discuss whether and how BoNT/A affects the spinal neuron–glia interaction and reduces the development of neuropathy.

  17. Chinese Medicinal Formula (MHGWT for Relieving Diabetic Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

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    Chia-I Tsai

    2013-01-01

    Full Text Available Objective. To investigate the effects of modified Hungqi Guizhi Wuwu Tang (MHGWT, a formula that comprises Chinese medicinal herbs, in relieving neuropathic pain in diabetics. Method. Between March 2008 and April 2009, 112 participants were randomly assigned to either the MHGWT group, whose members received MHGWT (n=56, or the control group, whose members received a placebo (n=56. Diabetic neuropathic pain (DNP was rated using the 15-item Short-Form Brief Pain Inventory (SF-BPI, the 17-item Short-Form McGill Pain Questionnaire (SF-MPQ, the 13-item Modified Michigan Neuropathy Screening Instrument (MMNSI, and the 36-item “SF-36.” Nerve conduction studies (NCSs were performed before and after treatment. Results. After 12 weeks of treatment, the SF-MPQ and SF-BPI scores of the MHGWT group were significantly (P0.05 reduced, and no significant difference in NCS level was observed between the groups (P>0.05. Conclusions. MHGWT shows promise in relieving DNP and deserves further investigation.

  18. Neuron–Glia Crosstalk and Neuropathic Pain: Involvement in the Modulation of Motor Activity in the Orofacial Region

    Science.gov (United States)

    Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Kitagawa, Junichi

    2017-01-01

    Neuropathic orofacial pain (NOP) is a debilitating condition. Although the pathophysiology remains unclear, accumulating evidence suggests the involvement of multiple mechanisms in the development of neuropathic pain. Recently, glial cells have been shown to play a key pathogenetic role. Nerve injury leads to an immune response near the site of injury. Satellite glial cells are activated in the peripheral ganglia. Various neural and immune mediators, released at the central terminals of primary afferents, lead to the sensitization of postsynaptic neurons and the activation of glia. The activated glia, in turn, release pro-inflammatory factors, further sensitizing the neurons, and resulting in central sensitization. Recently, we observed the involvement of glia in the alteration of orofacial motor activity in NOP. Microglia and astroglia were activated in the trigeminal sensory and motor nuclei, in parallel with altered motor functions and a decreased pain threshold. A microglial blocker attenuated the reduction in pain threshold, reduced the number of activated microglia, and restored motor activity. We also found an involvement of the astroglial glutamate–glutamine shuttle in the trigeminal motor nucleus in the alteration of the jaw reflex. Neuron–glia crosstalk thus plays an important role in the development of pain and altered motor activity in NOP. PMID:28954391

  19. Neuron-Glia Crosstalk and Neuropathic Pain: Involvement in the Modulation of Motor Activity in the Orofacial Region.

    Science.gov (United States)

    Hossain, Mohammad Zakir; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Kitagawa, Junichi

    2017-09-26

    Neuropathic orofacial pain (NOP) is a debilitating condition. Although the pathophysiology remains unclear, accumulating evidence suggests the involvement of multiple mechanisms in the development of neuropathic pain. Recently, glial cells have been shown to play a key pathogenetic role. Nerve injury leads to an immune response near the site of injury. Satellite glial cells are activated in the peripheral ganglia. Various neural and immune mediators, released at the central terminals of primary afferents, lead to the sensitization of postsynaptic neurons and the activation of glia. The activated glia, in turn, release pro-inflammatory factors, further sensitizing the neurons, and resulting in central sensitization. Recently, we observed the involvement of glia in the alteration of orofacial motor activity in NOP. Microglia and astroglia were activated in the trigeminal sensory and motor nuclei, in parallel with altered motor functions and a decreased pain threshold. A microglial blocker attenuated the reduction in pain threshold, reduced the number of activated microglia, and restored motor activity. We also found an involvement of the astroglial glutamate-glutamine shuttle in the trigeminal motor nucleus in the alteration of the jaw reflex. Neuron-glia crosstalk thus plays an important role in the development of pain and altered motor activity in NOP.

  20. An improved behavioural assay demonstrates that ultrasound vocalizations constitute a reliable indicator of chronic cancer pain and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Selvaraj Deepitha

    2010-03-01

    Full Text Available Abstract Background On-going pain is one of the most debilitating symptoms associated with a variety of chronic pain disorders. An understanding of mechanisms underlying on-going pain, i.e. stimulus-independent pain has been hampered so far by a lack of behavioural parameters which enable studying it in experimental animals. Ultrasound vocalizations (USVs have been proposed to correlate with pain evoked by an acute activation of nociceptors. However, literature on the utility of USVs as an indicator of chronic pain is very controversial. A majority of these inconsistencies arise from parameters confounding behavioural experiments, which include novelty, fear and stress due to restrain, amongst others. Results We have developed an improved assay which overcomes these confounding factors and enables studying USVs in freely moving mice repetitively over several weeks. Using this improved assay, we report here that USVs increase significantly in mice with bone metastases-induced cancer pain or neuropathic pain for several weeks, in comparison to sham-treated mice. Importantly, analgesic drugs which are known to alleviate tumour pain or neuropathic pain in human patients significantly reduce USVs as well as mechanical allodynia in corresponding mouse models. Conclusions We show that studying USVs and mechanical allodynia in the same cohort of mice enables comparing the temporal progression of on-going pain (i.e. stimulus-independent pain and stimulus-evoked pain in these clinically highly-relevant forms of chronic pain.

  1. Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

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    VENKATA R.K. THIAGARAJAN

    2014-09-01

    Full Text Available The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS, reduced glutathione (GSH and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

  2. Synthesis and Analgesic Effects of μ-TRTX-Hhn1b on Models of Inflammatory and Neuropathic Pain

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    Yu Liu

    2014-08-01

    Full Text Available μ-TRTX-Hhn1b (HNTX-IV is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. μ-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of μ-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of μ-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that μ-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.

  3. Reduction of painful area as new possible therapeutic target in post-herpetic neuropathic pain treated with 5% lidocaine medicated plaster: a case series

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    Casale R

    2014-06-01

    Full Text Available Roberto Casale,1,2 Maria Di Matteo,3,7 Cristina E Minella,4,7 Guido Fanelli,5,7 Massimo Allegri4,6,71Department of Clinical Neurophysiology and Pain Rehabilitation Unit, Foundation Salvatore Maugeri, IRCCS, Pavia, 2EFIC Montescano School, Montescano, 3Anesthesia and Intensive Care I, 4Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, 5Department of Anesthesia, Intensive Care and Pain Therapy, Azienda Ospedaliera Universitaria Parma, University of Parma, Parma, 6Department of Clinical, Surgical, Diagnostic and Pediatric Science, University of Pavia, Pavia, 7Study In Multidisciplinary Pain Research Group, Parma, ItalyAbstract: Post-herpetic neuralgia (PHN is neuropathic pain persisting after an acute episode of herpes zoster, and is associated with severe pain and sensory abnormalities that adversely affect the patient's quality of life and increase health care costs. Up to 83% of patients with PHN describe localized neuropathic pain, defined as “a type of neuropathic pain characterized by consistent and circumscribed area(s of maximum pain”. Topical treatments have been suggested as a first-line treatment for localized neuropathic pain. Use of 5% lidocaine medicated plaster could reduce abnormal nervous peripheral discharge and via the plaster could have a “protective” function in the affected area. It has been suggested that use of this plaster could reduce pain as well as the size of the painful area. To evaluate this possible outcome, we retrospectively reviewed eight patients with PHN, treated using 5% lidocaine medicated plaster. During a follow-up period of 3 months, we observed good pain relief, which was associated with a 46% reduction in size of the painful area after one month (from 236.38±140.34 cm2 to 128.80±95.7 cm2 and a 66% reduction after 3 months (81.38±59.19 cm2. Our study cohort was composed mainly of elderly patients taking multiple drugs to treat comorbidities, who have a high risk of drug

  4. Treatment of neuropathic cancer pain with continuous intrathecal administration of S (+)-ketamine

    NARCIS (Netherlands)

    Vranken, J. H.; van der Vegt, M. H.; Kal, J. E.; Kruis, M. R.

    2004-01-01

    The effective treatment of patients suffering from neuropathic cancer pain remains a clinical challenge. When patients experience either insufficient analgesia or problematic side-effects after opioid administration, intrathecal administration of morphine and other medications such as bupivacaine

  5. TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States

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    Laura Batti

    2016-06-01

    Full Text Available Neuropathic pain is a widespread chronic pain state that results from injury to the nervous system. Spinal microglia play a causative role in the pathogenesis of neuropathic pain through secretion of growth factors and cytokines. Here, we investigated the contribution of TMEM16F, a protein that functions as a Ca2+-dependent ion channel and a phospholipid scramblase, to microglial activity during neuropathic pain. We demonstrate that mice with a conditional ablation of TMEM16F in microglia do not develop mechanical hypersensitivity upon nerve injury. In the absence of TMEM16F, microglia display deficits in process motility and phagocytosis. Moreover, loss of GABA immunoreactivity upon injury is spared in TMEM16F conditional knockout mice. Collectively, these data indicate that TMEM16F is an essential component of the microglial response to injury and suggest the importance of microglial phagocytosis in the pathogenesis of neuropathic pain.

  6. Pharmacologic management of neuropathic pain: Evidence-based recommendations

    DEFF Research Database (Denmark)

    Dworkin, Robert H.; O'Connor, Alec B.; Backonja, Miroslav

    2007-01-01

    Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered...... and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second......, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs...

  7. Management of diabetic neuropathic foot and ankle malunions and nonunions

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    John J. Stapleton

    2011-05-01

    Full Text Available The management of diabetic neuropathic foot and ankle malunions and/or nonunions is often complicated by the presence of broken or loosened hardware, Charcot joints, infection, osteomyelitis, avascular bone necrosis, unstable deformities, bone loss, disuse and pathologic osteopenia, and ulcerations. The author discusses a rational approach to functional limb salvage with various surgical techniques that are aimed at achieving anatomic alignment, long-term osseous stability, and adequate soft tissue coverage. Emphasis is placed on techniques to overcome the inherent challenges that are encountered when surgically managing a diabetic nonunion and/or malunion. Particular attention is directed to the management of deep infection and Charcot neuroarthropathy in the majority of the cases presented.

  8. [Preoperative, neuropathic component in patients with back pain].

    Science.gov (United States)

    Lee, Y-J; Koch, E M W; Breidebach, J B; Bornemann, R; Wirtz, D C; Pflugmacher, R

    2017-04-01

    The objectification of pain is essential for evaluation, treatment plan and follow-up; therefore, it is necessary to find reliable clinical parameters. The goal of the study was the preoperative screening of a neuropathic component in patients with vertebral compression fracture (WKF), herniated disc (NPP) or spinal cord compression (SKS). Depending on the preoperative condition on admittance, patients were classified into three groups: group 1 WKF, group 2 NPP and group 3 SKS. To characterize the pain we used the painDETECT questionnaire, the Oswestry questionnaire and further questionnaires. All patients were surgically treated according to the diagnosis, e.g. radiofrequency kyphoplasty, nucleotomy or spondylodesis. We evaluated the data from 139 patients (45% WKF, 34% NPP and 21% SKS). There were no differences in preoperative pain intensity (median ordinal scale 0-10) with a mean preoperative score of 7 for all groups. The total score of the painDETECT questionnaire showed significantly higher results in group 2 (median 18) and in group 3 (median 14) than in group 1 (median 9). There was even a significant difference between groups 2 and 3 (p = 0.03). The highest pain intensity was detected in group 1 with a median visual analog scale (VAS) of 71 mm. The total scores in the painDETECT questionnaire and the scores in the Oswestry questionnaire correlated in groups 2 and 3. The painDETECT questionnaire was shown to be a very suitable instrument for evaluating the neuropathic pain component in patients with dorsalgia. This could be very useful in planning further therapy.

  9. Biopsychosocial characteristics of patients with neuropathic pain following spinal cord trauma injury. Case reports

    OpenAIRE

    Silva,Viviana Gonçalves; Jesus,Cristine Alves Costa de

    2015-01-01

    ABSTRACTBACKGROUND AND OBJECTIVES:Spinal cord injury is a change in spinal canal structures and may induce motor, sensory, autonomic and psychoaffective changes. Trauma injury is the most prevalent. Neuropathic pain is more frequent in people with spinal cord injury and may be disabling. Pain development mechanism is poorly known being its management difficult for both patients and health professionals. This study aimed at identifying biopsychosocial characteristics associated to neuropathic ...

  10. Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain.

    Science.gov (United States)

    Zhang, Jin; Wu, Dan; Xie, Cheng; Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

    2013-01-01

    Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.

  11. Neuropathic arthropathy of the shoulder interpreted as neoplasic lesion (reports of two cases)

    International Nuclear Information System (INIS)

    Galvis Ramirez, Javier Fernando; Soto, Camilo; Escandon, Santiago

    2006-01-01

    The neuropathic arthropathy is an illness that destroys the articulation, associated to loss of the propiocepcion. Inside the main causes they are the syringomyelia, tertiary syphilis and diabetes mellitus. In the superior member the frequently affected articulation is the glen humeral. In this report two patients are presented with neuropathic arthropathy from the shoulder secondary to syringomyelia and remitted to orthopedic oncology with diagnosis of condrosarcoma. The clinical radiological presentation and the differential diagnosis are analyzed

  12. Diagnosis and management of neuropathic pain: a balanced approach to treatment.

    Science.gov (United States)

    Nicholson, Bruce D

    2003-12-01

    To provide nurse practitioners with a conceptual framework from which to diagnose and manage chronic neuropathic pain, specifically postherpetic neuralgia (PHN). A current review of the available treatment options for the management of neuropathic pain and PHN is provided. A comprehensive literature review was conducted. Clinical articles, meta-analyses, and reviews were selected for their relevance to the diagnosis and management of chronic neuropathic pain and PHN. Managing patients with chronic neuropathic pain is a common clinical challenge due to variability in individual symptoms, mechanisms, and treatment responses. In patients with PHN, a balanced treatment approach focusing on efficacy, safety, and tolerability is recommended. With appropriate treatment, most patients are able to achieve clinically significant relief from neuropathic pain. Diagnosis and management of neuropathic pain syndromes is challenging. Because of the complexity of chronic pain, successful long-term treatment can be especially difficult (Nicholson, 2003b). While most acute pain is nociceptive (i.e., a response to noxious stimuli), chronic pain can be nociceptive, neuropathic, or of mixed origin. PHN is a chronic pain syndrome that can last for years, causing physical and social disability and psychological distress (Kanazi, 2000). Despite major recent advances in the treatment of PHN, many patients remain refractory to current therapy (Dworkin, 2003). For practicing clinicians, including nurse practitioners, viewing pain as a disease rather than a symptom is the first step towards its successful management. Understanding the pathophysiology of chronic pain and emerging treatment paradigms for the management of neuropathic pain and PHN is critical to optimal care.

  13. Nerve Regenerative Effects of GABA-B Ligands in a Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Valerio Magnaghi

    2014-01-01

    Full Text Available Neuropathic pain arises as a direct consequence of a lesion or disease affecting the peripheral somatosensory system. It may be associated with allodynia and increased pain sensitivity. Few studies correlated neuropathic pain with nerve morphology and myelin proteins expression. Our aim was to test if neuropathic pain is related to nerve degeneration, speculating whether the modulation of peripheral GABA-B receptors may promote nerve regeneration and decrease neuropathic pain. We used the partial sciatic ligation- (PSL- induced neuropathic model. The biochemical, morphological, and behavioural outcomes of sciatic nerve were analysed following GABA-B ligands treatments. Simultaneous 7-days coadministration of baclofen (10 mg/kg and CGP56433 (3 mg/kg alters tactile hypersensitivity. Concomitantly, specific changes of peripheral nerve morphology, nerve structure, and myelin proteins (P0 and PMP22 expression were observed. Nerve macrophage recruitment decreased and step coordination was improved. The PSL-induced changes in nociception correlate with altered nerve morphology and myelin protein expression. Peripheral synergic effects, via GABA-B receptor activation, promote nerve regeneration and likely ameliorate neuropathic pain.

  14. Tanshinone IIA attenuates neuropathic pain via inhibiting glial activation and immune response.

    Science.gov (United States)

    Cao, Fa-Le; Xu, Min; Wang, Yan; Gong, Ke-Rui; Zhang, Jin-Tao

    2015-01-01

    Neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia, is a devastating neurological disease that seriously affects patients' quality of life. We have previously shown that tanshinone IIA (TIIA), an important lipophilic component of Danshen, had significant anti-nociceptive effect in somatic and visceral pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA on neuropathic pain and the underlying mechanisms. Therefore, in the present study, by using spinal nerve ligation (SNL) pain model, the antinociceptive and antihyperalgesic effects of TIIA on neuropathic pain were evaluated by intraperitoneal administration in rats. The results indicated that TIIA dose-dependently inhibited SNL-induced mechanical hyperalgesia. As revealed by OX42 levels, TIIA effectively repressed the activation of spinal microglial activation in SNL-induced neuropathic pain. Meanwhile, TIIA also decreased the expressions of inflammatory cytokines TNF-α and IL-1β in the spinal cord. Furthermore, TIIA inhibited oxidative stress by significantly rescuing the superoxide dismutase (SOD) activity and decreasing the malondialdehyde (MDA). Moreover, TIIA depressed SNL-induced MAPKs activation in spinal cord. Taken together, our study provides evidence that TIIA inhibited SNL-induced neuropathic pain through depressing microglial activation and immune response by the inhibition of mitogen-activated protein kinases (MAPKs) pathways. Our findings suggest that TIIA might be a promising agent in the treatment of neuropathic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Effects of fisetin on oxaliplatin-induced neuropathic pain in mice

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    Hong Liu

    2015-03-01

    Full Text Available Common chemotherapeutic agents such as oxaliplatin often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is difficult to treat and responds poorly to common analgesics, which represents a challenging clinical issue. Fisetin is a naturally occurring flavonoid and this study tested the potential anti-hyperalgesic effects of fisetin in a mice model of oxaliplatin-induced neuropathic pain. Fisetin (1-4 mg/kg, i.p. did not significantly alter the mechanical hypersensitivity in oxaliplatin-treated mice but produced a dose-dependent anti-hyperalgesic effect during repeated treatment. Repeated treatment with fisetin also prevented chronic neuropathic pain-induced depressive-like behavior in a forced swimming test. Both the antihyperalgesic and the antidepressant-like effects of fisetin can be blocked by a selective 5-HT1A receptor antagonist WAY100635 (1 mg/kg. Together, these results demonstrate that fisetin has significant analgesic efficacy against chronic neuropathic pain, which could be a useful analgesic in the management of neuropathic pain.

  16. A tactile stimulus applied to the leg improves postural stability in young, old and neuropathic subjects.

    Science.gov (United States)

    Menz, Hylton B; Lord, Stephen R; Fitzpatrick, Richard C

    2006-10-02

    The purpose of this study was to determine whether the application of passive tactile cues to the lower limb could improve postural stability in healthy young controls, older people and people with diabetic peripheral neuropathy. Antero-posterior sway was measured with eyes open and closed in 10 healthy young subjects (mean age 27 years, 5 male, 5 female), 10 older subjects without diabetic peripheral neuropathy (mean age 88 years, 2 male, 8 female) and 10 subjects with diabetic peripheral neuropathy (mean age 65 years, 6 male, 4 female) while a small piece of Velcro attached to a flexible mount was applied to three different sites on the leg (ankle, calf, and knee). Across all conditions, the mean sway of the neuropathic subjects was 93% greater than for the young subjects and 11% more than the older subjects. On average, subjects swayed 10% more with the eyes closed than with the eyes open. Each stimulus reduced sway, but the effect increased approximately in proportion to the height of the stimulus above the ankles (ankle 7.6%, calf 13.5%, knee 20.1% reduction compared to the no stimulus condition). This experiment demonstrates that a passive stimulus applied to the skin of the leg, which provides sensory information about body movement, significantly reduces body sway during standing. This applies to older subjects and subjects with peripheral neuropathy as well as healthy young subjects. These results have implications for novel approaches for improving stability in people with peripheral sensory loss.

  17. Studies of experimental hosiery in diabetic neuropathic patients with high foot pressures.

    Science.gov (United States)

    Veves, A; Masson, E A; Fernando, D J; Boulton, A J

    1990-05-01

    High plantar pressures and painless trauma are associated with the development of foot ulcers in diabetic patients. Padded hosiery has been reported to reduce plantar pressures in patients at risk of ulceration. Using the optical pedobarograph we have studied 10 patients who regularly wore experimental padded hosiery for 6 months. The hosiery continued to provide substantial and significant reduction in peak forefoot pressures at 3 months (mean reduction 15.5%, p less than 0.01) and 6 months (17.6%, p less than 0.01), although the level of reduction was less than that seen at baseline (31.3%, p less than 0.05). In addition, commercially available hosiery designed as sportswear has been tested, and compared with experimental hosiery. Although these socks (with high or medium density padding) provided significant pressure reduction versus barefoot (mean 17.4% and 10.4%, p less than 0.01), this was not as great as that seen with experimental hosiery (27%, p less than 0.05). Thus the use of socks designed to reduce pressure stress on diabetic neuropathic feet is effective, and continues to be so for a considerable period of time. Commercially available sports socks may also have a place in the management of the diabetic insensitive foot.

  18. Analgesic Effect of Indian Gooseberry (Emblica officinalis Fruit Extracts on Postoperative and Neuropathic Pain in Rats

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    Dong Wook Lim

    2016-11-01

    Full Text Available Indian gooseberry (Emblica officinalis fruit, also known as “Amla” is one of the oldest edible fruits known in India. It has also traditionally been used to treat inflammation, and as an analgesic to treat wounds. However, experimental evidence for the analgesic effects of E. officinalis has been lacking. The present study investigated whether E. officinalis extracts exhibit analgesic effects in the plantar incision (PI and spared nerve injury (SNI pain-model rats. We evaluated the mechanical withdrawal threshold (MWT using von Frey filaments, and pain-related behavior was determined after surgery based on ultrasonic vocalization (USV. The group treated with E. officinalis extracts at 300 mg/kg had significantly increased MWT values at 6 h and 24 h after the PI, and had a significantly reduced number of 22–27-kHz USVs at 6 h and 24 h after PI. Moreover, after 15 days of continuous treatment with E. officinalis extracts, the treated group showed significantly alleviated SNI-induced hypersensitivity and reduced pro-inflammatory cytokine levels. Thus, E. officinalis extracts have potential analgesic effects in both postoperative and neuropathic pain models in vivo.

  19. Effects of Sex and Stress on Trigeminal Neuropathic Pain-Like Behavior in Rats.

    Science.gov (United States)

    Korczeniewska, Olga Anna; Khan, Junad; Tao, Yuanxiang; Eliav, Eli; Benoliel, Rafael

    2017-01-01

    To investigate the effects and interactions of sex and stress (provoked by chronic restraint [RS]) on pain-like behavior in a rat model of trigeminal neuropathic pain. The effects of sex and RS (carried out for 14 days as a model for stress) on somatosensory measures (reaction to pinprick, von Frey threshold) in a rat model of trigeminal neuropathic pain were examined. The study design was 2 × 4, with surgery (pain) and sham surgery (no pain) interacting with male restrained (RS) and unrestrained (nRS) rats and female RS and nRS rats. A total of 64 Sprague Dawley rats (32 males and 32 females) were used. Half of the animals in each sex group underwent RS, and the remaining half were left unstressed. Following the RS period, trigeminal neuropathic pain was induced by unilateral infraorbital nerve chronic constriction injury (IOCCI). Half of the animals in the RS group and half in the nRS group (both males and females) were exposed to IOCCI, and the remaining halves to sham surgery. Elevated plus maze (EPM) assessment and plasma interferon gamma (IFN-γ) levels were used to measure the effects of RS. Analysis of variance (ANOVA) was used to assess the effects of stress, sex, and their interactions on plasma IFN-γ levels, changes in body weight, EPM parameters, tactile allodynia, and mechanohyperalgesia. Pairwise comparisons were performed by using Tukey post hoc test corrected for multiple comparisons. Both male and female RS rats showed significantly altered exploratory behavior (as measured by EPM) and had significantly lower plasma IFN-γ levels than nRS rats. Rats exposed to RS gained weight significantly slower than the nRS rats, irrespective of sex. Following RS but before surgery, RS rats showed significant bilateral reductions in von Frey thresholds and significantly increased pinprick response difference scores compared to nRS rats, irrespective of sex. From 17 days postsurgery, RSIOCCI rats showed significantly reduced von Frey thresholds and

  20. Chemotherapy-related neuropathic symptom management: a randomized trial of an automated symptom-monitoring system paired with nurse practitioner follow-up.

    Science.gov (United States)

    Kolb, Noah Allan; Smith, Albert Gordon; Singleton, John Robinson; Beck, Susan L; Howard, Diantha; Dittus, Kim; Karafiath, Summer; Mooney, Kathi

    2018-05-01

    The purpose of this study was to evaluate a new care model to reduce chemotherapy-induced neuropathic symptoms. Neuropathic symptom usual care was prospectively compared to an automated symptom-monitoring and coaching system, SymptomCare@Home (SCH), which included nurse practitioner follow-up triggered by moderate to severe symptoms. Patients beginning chemotherapy were randomized to usual care (UC) or to the SCH intervention. This sub-analysis included only taxane/platin therapies. Participants called the automated telephone symptom-monitoring system daily to report numbness and tingling. The monitoring system recorded patient-reported neuropathic symptom severity, distress, and activity interference on a 0-10 scale. UC participants were instructed to call their oncologist for symptom management. SCH participants with symptom severity of ≥ 4 received automated self-care strategies, and a nurse practitioner (NP) provided guideline-based care. There were 252 participants, 78.6% of which were female. Mean age was 55.1 years. Mean follow-up was 90.2 ± 39.9 days (81.1 ± 40.3 calls). SCH participants had fewer days of moderate (1.8 ± 4.0 vs. 8.6 ± 17.3, p < 0.001) and severe chemotherapy-induced peripheral neuropathy symptoms (0.3 ± 1.0 vs. 1.1 ± 5.2, p = 0.006). SCH participants had fewer days with moderate and severe symptom-related distress (1.4 ± 3.7 vs. 6.9 ± 15.0, p < 0.001; 0.2 ± 0.9 vs. 1.5 ± 6.1, p = 0.001) and trended towards less activity interference (3.3 ± 1.9 vs. 3.8 ± 2.1, p = 0.08). Other neuropathic symptoms were addressed in 5.8-15.4% of SCH follow-up calls. The SCH system effectively identified neuropathic symptoms and their severity and, paired with NP follow-up, reduced symptom prevalence, severity, and distress compared to usual care.

  1. Long non-coding RNA CCAT1 modulates neuropathic pain progression through sponging miR-155

    OpenAIRE

    Dou, Lidong; Lin, Hongqi; Wang, Kaiwei; Zhu, Guosong; Zou, Xuli; Chang, Enqiang; Zhu, Yongfeng

    2017-01-01

    Neuropathic pain is caused by dysfunction or primary injury of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) play important roles in the development of neuropathic pain. However, the effects of lncRNA colon cancer associated transcript-1 (CCAT1) in neuropathic pain have not been reported. The model of bilateral sciatic nerve chronic constriction injuries (bCCI) is regarded as long-lasting mechanical hypersensitivity and cold allodynia, which is the representative symptom in ...

  2. Spinal neuropeptide expression and neuropathic behavior in the acute and chronic phases after spinal cord injury: Effects of progesterone administration.

    Science.gov (United States)

    Coronel, María F; Villar, Marcelo J; Brumovsky, Pablo R; González, Susana L

    2017-02-01

    Patients with spinal cord injury (SCI) develop chronic pain that severely compromises their quality of life. We have previously reported that progesterone (PG), a neuroprotective steroid, could offer a promising therapeutic strategy for neuropathic pain. In the present study, we explored temporal changes in the expression of the neuropeptides galanin and tyrosine (NPY) and their receptors (GalR1 and GalR2; Y1R and Y2R, respectively) in the injured spinal cord and evaluated the impact of PG administration on both neuropeptide systems and neuropathic behavior. Male rats were subjected to spinal cord hemisection at T13 level, received daily subcutaneous injections of PG or vehicle, and were evaluated for signs of mechanical and thermal allodynia. Real time PCR was used to determine relative mRNA levels of neuropeptides and receptors, both in the acute (1day) and chronic (28days) phases after injury. A significant increase in Y1R and Y2R expression, as well as a significant downregulation in GalR2 mRNA levels, was observed 1day after SCI. Interestingly, PG early treatment prevented Y1R upregulation and resulted in lower NPY, Y2R and GalR1 mRNA levels. In the chronic phase, injured rats showed well-established mechanical and cold allodynia and significant increases in galanin, NPY, GalR1 and Y1R mRNAs, while maintaining reduced GalR2 expression. Animals receiving PG treatment showed basal expression levels of galanin, NPY, GalR1 and Y1R, and reduced Y2R mRNA levels. Also, and in line with previously published observations, PG-treated animals did not develop mechanical allodynia and showed reduced sensitivity to cold stimulation. Altogether, we show that SCI leads to considerable changes in the spinal expression of galanin, NPY and their associated receptors, and that early and sustained PG administration prevents them. Moreover, our data suggest the participation of galaninergic and NPYergic systems in the plastic changes associated with SCI-induced neuropathic pain

  3. The characteristics of chronic pain after non-traumatic, non-compressive myelopathy: Focus on neuropathic pain.

    Science.gov (United States)

    Eom, Young In; Kim, Min; Joo, In Soo

    2017-05-01

    The aim of this study was to assess the characteristics of neuropathic pain after non-traumatic, non-compressive (NTNC) myelopathy and find potential predictors for neuropathic pain. We analyzed 54 patients with NTNC myelopathy. The Short Form McGill Pain Questionnaire (SF-MPQ) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were used to assess pain. Health-related QOL was evaluated by the Short Form 36-item (SF-36) health survey. Out of 48 patients with pain, 16 (33.3%) patients experienced neuropathic pain. Mean age was significantly lower in patients with neuropathic pain than in patients with non-neuropathic pain (39.1 ± 12.5 vs. 49.8 ± 9.3, P = 0.002). There were no statistically significant differences in the other variables including sex, etiology of myelopathy, pain and QOL scores between the two groups. A binary logistic regression revealed that onset age under 40, and non-idiopathic etiology were independent predictors of the occurrence of neuropathic pain. Both SF-MPQ and LANSS scores were significantly correlated with SF-36 scores, adjusted by age, sex, presence of diabetes mellitus, and current EDSS scores (r = -0.624, P Neuropathic pain must be one of serious complications in patients with NTNC myelopathy and also affects their quality of life. Onset age and etiology of myelopathy are important factors in the development of neuropathic pain in NTNC myelopathy.

  4. Ameliorative effect of ethyl pyruvate in neuropathic pain induced by chronic constriction injury of sciatic nerve

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    Varsha J. Bansode

    2014-01-01

    Full Text Available Objective: The present study was designed to investigate the ameliorative effects of ethyl pyruvate (EP in chronic constriction injury (CCI-induced painful neuropathy in rats. Materials and Methods: EP 50 and 100 mg/kg was administered for 21 consecutive days starting from the day of surgery. The effects of EP in the paw pressure, acetone drop, and tail heat immersion tests were assessed, reflecting the degree of mechanical hyperalgesia, cold allodynia, and spinal thermal sensation, respectively. Axonal degeneration of the sciatic nerve was assessed histopathologically. The levels of thiobarbituric acid reactive species, reduced glutathione (GSH, catalase (CAT, and superoxide dismutase (SOD were determined to assess oxidative stress. Key Findings: Administration of 50 and 100 mg/kg EP attenuated the reduction of nociceptive threshold in the paw pressure, acetone drop, and tail heat immersion tests. EP 100 mg/kg significantly attenuated reactive changes in histopathology and increase in oxidative stress. Conclusion: EP 100 mg/kg showed beneficial activity against nerve trauma-induced neuropathy. Hence, it can be used as a better treatment option in neuropathic pain (NP. The observed antinociceptive effects of EP may possibly be attributed to its antioxidant and anti-inflammatory activity.

  5. An Intensive Locomotor Training Paradigm Improves Neuropathic Pain following Spinal Cord Compression Injury in Rats.

    Science.gov (United States)

    Dugan, Elizabeth A; Sagen, Jacqueline

    2015-05-01

    Spinal cord injury (SCI) is often associated with both locomotor deficits and sensory dysfunction, including debilitating neuropathic pain. Unfortunately, current conventional pharmacological, physiological, or psychological treatments provide only marginal relief for more than two-thirds of patients, highlighting the need for improved treatment options. Locomotor training is often prescribed as an adjunct therapy for peripheral neuropathic pain but is rarely used to treat central neuropathic pain. The goal of this study was to evaluate the potential anti-nociceptive benefits of intensive locomotor training (ILT) on neuropathic pain consequent to traumatic SCI. Using a rodent SCI model for central neuropathic pain, ILT was initiated either 5 d after injury prior to development of neuropathic pain symptoms (the "prevention" group) or delayed until pain symptoms fully developed (∼3 weeks post-injury, the "reversal" group). The training protocol consisted of 5 d/week of a ramping protocol that started with 11 m/min for 5 min and increased in speed (+1 m/min/week) and time (1-4 minutes/week) to a maximum of two 20-min sessions/d at 15 m/min by the fourth week of training. ILT prevented and reversed the development of heat hyperalgesia and cold allodynia, as well as reversed developed tactile allodynia, suggesting analgesic benefits not seen with moderate levels of locomotor training. Further, the analgesic benefits of ILT persisted for several weeks once training had been stopped. The unique ability of an ILT protocol to produce robust and sustained anti-nociceptive effects, as assessed by three distinct outcome measures for below-level SCI neuropathic pain, suggests that this adjunct therapeutic approach has great promise in a comprehensive treatment strategy for SCI pain.

  6. The clinical characteristics of neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Celik, E C; Erhan, B; Lakse, E

    2012-08-01

    The aim of the study was to evaluate the characteristics of neuropathic pain and observe intensity alterations in pain with regard to time during the day in spinal cord injury (SCI) patients. A total of 50 SCI patients (M/F, 40/10; mean age, 35±12 years) with at-level and below-level neuropathic pain were included in the study. All patients were examined and classified according to the ASIA/ISCoS 2002 International Neurologic Examination and Classification Standards. The history, duration, localization and characteristics of the pain were recorded. Neuropathic pain of patients was evaluated with the McGill-Melzack Pain Questionnaire and LANSS (Leeds Assessment of Neuropathic Symptoms and Signs) Pain Scale. Visual analog scale (VAS) was used to measure the severity of pain four times during the day. Quality of life was analyzed with Short Form 36. Out of 50 patients, 10 were tetraplegic and 40 were paraplegic. In all, 28 patients had motor and sensory complete injuries (AIS A), whereas 22 patients had sensory incomplete (AIS B, C and D) injuries. The most frequently used words to describe neuropathic pain were throbbing, tiring, hot and tingling. Pain intensity was significantly higher in the night than in the evening, noon and morning (PNeuropathic pain is a serious complaint in SCI patients and affects their quality of life. Neuropathic pain intensity was higher in the night hours than other times of day. This situation reinforces the need for a continued research and education on neuropathic pain in SCI.

  7. Neuropathic pain in the orofacial region: The role of pain history. A retrospective study.

    Science.gov (United States)

    Dieb, W; Moreau, N; Chemla, I; Descroix, V; Boucher, Y

    2017-06-01

    Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. The study was performed in the dental department of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n=2) did not report any prior pain and 23% (n=13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n=36) received surgical treatment; 61%, (n=25) endodontic treatment and 22%, (n=9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Chronic pain in Gaucher disease: skeletal or neuropathic origin?

    Science.gov (United States)

    Devigili, Grazia; De Filippo, Michele; Ciana, Giovanni; Dardis, Andrea; Lettieri, Christian; Rinaldo, Sara; Macor, Daniela; Moro, Alessandro; Eleopra, Roberto; Bembi, Bruno

    2017-08-31

    Pain is one of the most disabling symptoms of Gaucher disease. It is referred by the majority of Gaucher patients and often persists despite long-term enzyme replacement treatment. It has been mainly considered as nociceptive pain secondary to skeletal involvement but it is described even in the absence of bone disease without a clear explanation. In the last years an increasing number of reports have described the presence of neurological manifestation in Gaucher type 1 patients, including subclinical large fibre neuropathy. In our Gaucher clinic we have observed the recurrence of painful symptoms in a group of type 1 Gaucher patients even after a long-term enzyme replacement therapy. A cross-sectional study was designed to investigate the pathophysiology of pain in a cohort of 25 Gaucher patients (13 females, 12 males). Twenty-two patients received enzyme replacement therapy for a period of time ranging from 10 to >20 years, while three were new diagnosis. Pain was classified as bone or neurologic related on the basis of anamnestic data, clinical and electrophysilogical examinations. Intensity and quality of pain were recorded by Douleur Neuropathique en 4 questionnaire and Neuropathic Pain Symptom Inventory. Neuroalgological evaluation, quantitative sensory testing, nerve conduction studies and evaluation of epidermal nerve fibres density were performed. Comorbidities for peripheral neuropathy were excluded. Thirteen patients complained of pain suggestive of neuropathic origin with proximal patchy distribution, six manifested severe pain paroxysmal, nine pinprick hypoesthesia and 17 thermal hypoesthesia. At quantitative sensory testing, all of them showed high cold thresholds with errata sensation (burning instead of cold), paradoxical heat sensation and mechanic hypoesthesia; three patients showed pressure pain hyperalgesia. Epidermal denervation was present in 19 patients, 12 of them with non-length dependent pattern. These results confirm the role of

  9. Pain in chemotherapy-induced neuropathy--more than neuropathic?

    Science.gov (United States)

    Geber, Christian; Breimhorst, Markus; Burbach, Berenike; Egenolf, Christina; Baier, Bernhard; Fechir, Marcel; Koerber, Juergen; Treede, Rolf-Detlef; Vogt, Thomas; Birklein, Frank

    2013-12-01

    Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. Patients were characterized clinically through nerve conduction studies (NCS) and quantitative sensory testing (QST). Questionnaires for pain (McGill) and anxiety/depression (Hospital Anxiety and Depression Scale) were supplied. Patients were followed-up after 17 days. Large- (61%) and mixed- (35%) fibre neuropathies were more frequent than small-fibre neuropathy (1.4%). The 5 major chemotherapeutic regimens impacted differently on large- but not on small-fibre function and did not predict painfulness. Chronic pain associated with CIN was reported in 41.7%. Painless and painful CIN did not differ in QST profiles or electrophysiological findings, but different somatosensory patterns were found in CIN subgroups (pain at rest [RestP], n = 25; movement-associated pain [MovP], n = 15; both pain characteristics [MovP+RestP], n = 21; or no pain [NonP], n = 85): small-fibre function (cold-detection threshold, CDT: z score: -1.46 ± 0.21, P < 0.01) was most impaired in RestP; mechanical hyperalgesia was exclusively found in MovP (z score: +0.81 ± 0.30, P < 0.05). "Anxiety" discriminated between painful and painless CIN; "CDT" and "anxiety" discriminated between patients with ongoing (RestP) and movement-associated pain (MovP) or pain components (MovP+RestP). The detrimental effect of chemotherapy on large fibres failed to differentiate painful from painless CIN. Patients stratified for musculoskeletal or neuropathic pain, however, differed in psychological and somatosensory parameters. This stratification might allow for the application of a more specific therapy. Copyright © 2013

  10. Characterizing neuropathic pain profiles: enriching interpretation of painDETECT

    Directory of Open Access Journals (Sweden)

    Cappelleri JC

    2016-07-01

    Full Text Available Joseph C Cappelleri,1 Vijaya Koduru,2 E Jay Bienen,3 Alesia Sadosky4 1Pfizer Inc, Groton, CT, USA; 2Eliassen Group, New London, CT, USA; 3Outcomes Research Consultant, New York, NY, USA; 4Pfizer Inc, New York, NY, USA Purpose: To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropathic pain (NeP, for discriminating among sensory pain symptoms (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure. Methods: The seven-item version of painDETECT provides an overall score that targets only sensory symptoms, while the nine-item version adds responses on two items to the overall score, covering pain course pattern and pain radiation. Both versions have relevance in terms of characterizing broad NeP. The nine- and seven-item versions of painDETECT were administered to subjects with confirmed NeP across six conditions identified during office visits to US community-based physicians. Responses on the sensory symptom items were dichotomized into “at least moderate” (ie, moderate, strongly, very strongly relative to the combined other responses (never, hardly noticed, slightly. Logistic regression of dichotomized variables on the total painDETECT score provided probabilities of experiencing each symptom across the range of painDETECT scores. Results: Both painDETECT versions discriminated among the symptoms with similar probabilities across the score ranges. Using these data, the probability of moderately experiencing each pain sensory item was estimated for a particular score, providing a pain profile. Additionally, the likelihood of experiencing each sensation was determined for a discrete increase in score, ie, the odds of at least a moderate sensation of burning (versus less than a moderate sensation was 1.29 for a 1-point increase, 3.52 for a 5-point increase, and 12.42 for every 10-point increase in the nine-item painDETECT score

  11. A COMBINED EFFECT OF DEXTROMETHORPHAN AND MELATONIN ON NEUROPATHIC PAIN BEHAVIOR IN RATS

    Science.gov (United States)

    Wang, Shuxing; Zhang, Lin; Lim, Grewo; Sung, Backil; Tian, Yinghong; Chou, Chiu-Wen; Hernstadt, Hayley; Rusanescu, Gabriel; Ma, Yuxin; Mao, Jianren

    2009-01-01

    Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-D-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain. PMID:19595681

  12. Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients.

    Directory of Open Access Journals (Sweden)

    Andreas Binder

    Full Text Available Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K was associated with the presence of paradoxical heat sensation (p = 0.03, and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V with cold hypoalgesia (p = 0.0035. Two main subgroups characterized by preserved (1 and impaired (2 sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and pG (rs222747, M315I to cold hypaesthesia (p = 0.002, but there was absence of associations in subgroup 2. In this study we found no evidence that genetic

  13. Neuropathic Pain Experiences of Spinal Cord Injury Patients.

    Science.gov (United States)

    Li, Chin-Ching; Lin, Hung-Ru; Tsai, Ming-Dar; Tsay, Shiow-Luan

    2017-11-09

    Neuropathic pain (NP) is a common, severe problem that affects spinal cord injury (SCI) patients. Only SCI patients truly understand the impact and extent of this type of pain. The aim of this study was to understand the NP experienced by SCI patients and the influence of this type of pain on their daily life. A qualitative design was used. An interview guide including a semistructured questionnaire and in-depth interviews was conducted with SCI patients with NP in a neurorehabilitation department at a medical center in northern Taiwan. The data were collected using a purposive sampling method. Content analysis was performed on the interview data, which were obtained from 13 SCI patients with NP. Three themes and eight subthemes were identified that described the NP experience of the participants and the influence of NP on their daily life. The three themes included elusive pain (changing and individual pain sensations, erratically haunting threat, and phantom limb sensations), complicated feelings about pain (converting depression into an active attitude toward life, having feelings of anticipation and anxiety about future pain relief, and facing and experiencing pain), and renewed hope (bravely fighting pain and seeking pain relief methods). This study revealed three important themes of NP experienced by SCI patients, including elusive pain, complicated feelings about pain, and renewed hope. Nurses should understand the nature of NP, provide a thorough pain assessment, and design a proper pain management plan to care effectively for patients with NP.

  14. Herpes zoster induced neuropathic bladder--a case report.

    Science.gov (United States)

    Tsai, Hsiu-Nan; Wu, Wen-Jeng; Huang, Shu-Pin; Su, Chin-Ming; Chen, Chung-Chin; Wang, Chii-Jye; Chou, Yii-Her; Huang, Chun-Hsiung

    2002-01-01

    Herpes zoster infection involving the sacral dermatomes has been associated with bladder dysfunction and, although rarely, with acute urinary retention. Less than 150 cases have been reported in the literature. After reviewing our institute's chart records covering a period of time dating from 1991 to 2001, we found that three of our patients had developed acute urinary retention following herpes zoster skin lesions of the S2-4 dermatomes. Herein we report our findings. These three patients had previously been found to have normal voiding status. However, at the time of complaint urodynamic studies revealed detrusor areflexia or detrusor hyporeflexia with decreased sensation of bladder filling. After micturation recovery, repeat urodynamic studies revealed detrusor pressure and bladder sensation recovery. After one to six weeks of treatment, all three patients could void spontaneously without catheterization. We found that, when treated with antiviral medication, supportive analgesics, and temporary urinary drainage, which included urethral catheterization and suprapubic cystostomy, acute urinary retention associated with herpes zoster has a generally favorable prognosis. In other words, we found that in spite of its rarity, herpes zoster induced neuropathic bladder dysfunction is reversible when treated appropriately.

  15. Intravenous Ketamine Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization.

    Science.gov (United States)

    Maher, Dermot P; Chen, Lucy; Mao, Jianren

    2017-02-01

    Intravenous ketamine infusions have been used extensively to treat often-intractable neuropathic pain conditions. Because there are many widely divergent ketamine infusion protocols described in the literature, the variation in these protocols presents a challenge for direct comparison of one protocol with another and in discerning an optimal protocol. Careful examination of the published literature suggests that ketamine infusions can be useful to treat neuropathic pain and that certain characteristics of ketamine infusions may be associated with better clinical outcomes. Increased duration of relief from neuropathic pain is associated with (1) higher total infused doses of ketamine; (2) prolonged infusion durations, although the rate of infusion does not appear to be a factor; and (3) coadministration of adjunct medications such as midazolam and/or clonidine that mitigate some of the unpleasant psychomimetic side effects. However, there are few studies designed to optimize ketamine infusion protocols by defining what an effective infusion protocol entails with regard to a respective neuropathic pain condition. Therefore, despite common clinical practice, the current state of the literature leaves the use of ketamine infusions without meaningful guidance from high-quality comparative evidence. The objectives of this topical review are to (1) analyze the available clinical evidence related to ketamine infusion protocols and (2) call for clinical studies to identify optimal ketamine infusion protocols tailored for individual neuropathic pain conditions. The Oxford Center for Evidence-Based Medicine classification for levels of evidence was used to stratify the grades of clinical recommendation for each infusion variable studied.

  16. TNF α is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats

    Science.gov (United States)

    Zheng, Xuexing; Ouyang, Handong; Liu, Shue; Mata, Marina; Fink, David J.; Hao, Shuanglin

    2011-01-01

    In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTI). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current studies, we tested the role of TNFα in antiretroviral drug-induced neuropathic pain. We administered 2′,3′-dideoxycytidine (ddC, one of the NRTIs) systemically to induce mechanical allodynia. We found that ddC induced overexpression of both mRNA and proteins of GFAP and TNFα in the spinal dorsal horn. TNFα was colocalized with GFAP in the spinal dorsal horn and with NeuN in the DRG. Knockdown of TNFα with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNFα is involved in NRTI-induced neuropathic pain. PMID:21741472

  17. MiR-155 modulates the progression of neuropathic pain through targeting SGK3.

    Science.gov (United States)

    Liu, Shaoxing; Zhu, Bo; Sun, Yan; Xie, Xianfeng

    2015-01-01

    This study aimed to illustrate the potential effects of miR-155 in neuropathic pain and its potential mechanism. Spragure-Dawley (SD) rats were used for neuropathic pain model of bilateral chronic constriction injury (bCCI) construction. Effects of miR-155 expression on pain threshold of mechanical stimuli (MWT), paw withdrawal threshold latency (PMTL) and cold threshold were analyzed. Target for miR-155 was analyzed using bioinformatics methods. Moreover, effects of miR-155 target gene expression on pain thresholds were also assessed. Compared with the controls and sham group, miR-155 was overexpressed in neuropathic pain rats (P<0.05), but miR-155 slicing could significantly decreased the pain thresholds (P<0.05). Serum and glucocorticoid regulated protein kinase 3 (SGK3) was predicted as the target gene for miR-155, and miR-155 expression was negatively correlated to SGK3 expression. Furthermore, SGK3 overexpression could significantly decreased the pain thresholds which was the same as miR-155 (P<0.05). Moreover, miR-155 slicing and SGK3 overexpression could significantly decrease the painthreshold. The data presented in this study suggested that miR-155 slicing could excellently alleviate neuropathic pain in rats through targeting SGK3 expression. miR-155 may be a potential therapeutic target for neuropathic pain treatment.

  18. Neural markers of neuropathic pain associated with maladaptive plasticity in spinal cord injury.

    Science.gov (United States)

    Pascoal-Faria, Paula; Yalcin, Nilufer; Fregni, Felipe

    2015-04-01

    Given the potential use of neural markers for the development of novel treatments in spinal cord pain, we aimed to characterize the most effective neural markers of neuropathic pain following spinal cord injury (SCI). A systematic PubMed review was conducted, compiling studies that were published prior to April, 2014 that examined neural markers associated with neuropathic pain after SCI using electrophysiological and neuroimaging techniques. We identified 6 studies: Four using electroencephalogram (EEG); 1 using magnetic resonance imaging (MRI) and FDG-PET (positron emission tomography); and 1 using MR spectroscopy. The EEG recordings suggested a reduction in alpha EEG peak frequency activity in the frontal regions of SCI patients with neuropathic pain. The MRI scans showed volume loss, primarily in the gray matter of the left dorsolateral prefrontal cortex, and by FDG-PET, hypometabolism in the medial prefrontal cortex was observed in SCI patients with neuropathic pain compared with healthy subjects. In the MR spectroscopy findings, the presence of pain was associated with changes in the prefrontal cortex and anterior cingulate cortex. When analyzed together, the results of these studies seem to point out to a common marker of pain in SCI characterized by decreased cortical activity in frontal areas and possibly increased subcortical activity. These results may contribute to planning further mechanistic studies as to better understand the mechanisms by which neuropathic pain is modulated in patients with SCI as well as clinical studies investigating best responders of treatment. © 2014 World Institute of Pain.

  19. Blocking proteinase-activated receptor 2 alleviated neuropathic pain evoked by spinal cord injury.

    Science.gov (United States)

    Wei, H; Wei, Y; Tian, F; Niu, T; Yi, G

    2016-01-01

    Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Especially, neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effectively therapeutic agents and treatment strategies. Proteinase-activated receptors (PARs) are a family member of G-protein-coupled receptors and are activated by a proteolytic mechanism. One of its subtypes PAR2 has been reported to be engaged in mechanical and thermal hyperalgesia. Thus, in this study we specifically examined the underlying mechanisms responsible for SCI evoked-neuropathic pain in a rat model. Overall, we demonstrated that SCI increases PAR2 and its downstream pathways TRPV1 and TRPA1 expression in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal PAR2 by intrathecal injection of FSLLRY-NH2 significantly inhibits neuropathic pain responses induced by mechanical and thermal stimulation whereas FSLLRY-NH2 decreases the protein expression of TRPV1 and TRPA1 as well as the levels of substance P and calcitonin gene-related peptide. Results of this study have important implications, i.e. targeting one or more of these signaling molecules involved in activation of PAR2 and TRPV1/TRPA1 evoked by SCI may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

  20. Neuropathic pain screening questionnaires have limited measurement properties. A systematic review.

    Science.gov (United States)

    Mathieson, Stephanie; Maher, Christopher G; Terwee, Caroline B; Folly de Campos, Tarcisio; Lin, Chung-Wei Christine

    2015-08-01

    The Douleur Neuropathique 4 (DN4), ID Pain, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), PainDETECT, and Neuropathic Pain Questionnaire have been recommended as screening questionnaires for neuropathic pain. This systematic review aimed to evaluate the measurement properties (eg, criterion validity and reliability) of these questionnaires. Online database searches were conducted and two independent reviewers screened studies and extracted data. Methodological quality of included studies and the measurement properties were assessed against established criteria. A modified Grading of Recommendations Assessment, Development and Evaluation approach was used to summarize the level of evidence. Thirty-seven studies were included. Most studies recruited participants from pain clinics. The original version of the DN4 (French) and Neuropathic Pain Questionnaire (English) had the most number of satisfactory measurement properties. The ID Pain (English) demonstrated satisfactory hypothesis testing and reliability, but all other properties tested were unsatisfactory. The LANSS (English) was unsatisfactory for all properties, except specificity. The PainDETECT (English) demonstrated satisfactory hypothesis testing and criterion validity. In general, the cross-cultural adaptations had less evidence than the original versions. Overall, the DN4 and Neuropathic Pain Questionnaire were most suitable for clinical use. These screening questionnaires should not replace a thorough clinical assessment. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  1. Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

    Science.gov (United States)

    Kim, Jinhyung; Ryu, Sang Baek; Lee, Sung Eun; Shin, Jaewoo; Jung, Hyun Ho; Kim, Sung June; Kim, Kyung Hwan; Chang, Jin Woo

    2016-03-01

    Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

  2. Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo-controlled, double-blind clinical trial with amitriptyline as a comparator

    NARCIS (Netherlands)

    Vanelderen, P.; Zundert, J. Van; Kozicz, L.T.; Puylaert, M.; Vooght, P. De; Mestrum, R.; Heylen, R.; Roubos, E.W.; Vissers, K.C.P.

    2015-01-01

    BACKGROUND: Less than 50% of patients experience sufficient pain relief with current drug therapy for neuropathic pain. Minocycline shows promising results in rodent models of neuropathic pain but was not studied in humans with regard to the treatment of neuropathic pain. METHODS: In this

  3. Plantar fat-pad displacement in neuropathic diabetic patients with toe deformity: a magnetic resonance imaging study

    NARCIS (Netherlands)

    Bus, Sicco A.; Maas, Mario; Cavanagh, Peter R.; Michels, Robert P. J.; Levi, Marcel

    2004-01-01

    OBJECTIVE: The aim of this study was to quantify the association between claw/hammer toe deformity and changes in submetatarsal head (sub-MTH) fat-pad geometry in diabetic neuropathic feet. RESEARCH DESIGN AND METHODS: Thirteen neuropathic diabetic subjects (mean age 56.2 years) with toe deformity,

  4. Alternative treatment strategies for neuropathic pain: Role of Indian medicinal plants and compounds of plant origin-A review.

    Science.gov (United States)

    Singh, Hasandeep; Bhushan, Sakshi; Arora, Rohit; Singh Buttar, Harpal; Arora, Saroj; Singh, Balbir

    2017-08-01

    Neuropathic pain is a complex, chronic pain state accompanied by tissue injury and nerve damage. This important health issue constitutes a challenge for the modern medicine worldwide. The management of neuropathic pain remains a major clinical challenge, pertaining to an inadequate understanding of pathophysiological mechanisms of neuropathic pain. Various classes of drugs have been reported effective for the management of neuropathic pain viz. opiates, tricyclic antidepressants, and antiepileptic agents. However, association of adverse effects with these drugs hinders their confident prescription in people with neuropathic pain. Recently, various medicinal plants have been reported effective for the management of neuropathic pain. So, it may be prudent to look beyond synthetic drugs pertaining to their unprecedented pharmacotherapeutic effects with lesser adverse effects. The extensive literature review has been carried out from databases such as Science direct, Scifinder, Wiley online library, PubMed, Research gate, Google scholar and Chemical Abstracts. The list of Traditional Indian Medicinal plants (TIMPs) and isolated compounds have been compiled which have been reported effective as an alternative therapy for the management of neuropathic pain. This helps the researchers to discover some novel therapeutic agents against neuropathic pain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Pharmacological correlation between the formalin test and the neuropathic pain behavior in different species with chronic constriction injury.

    NARCIS (Netherlands)

    Vissers, K.C.P.; Geenen, F.; Biermans, R.; Meert, T.F.

    2006-01-01

    Research on mechanisms of drug action, and preclinical screening of molecules with a potential activity on neuropathic pain requires extensive animal work. The chronic constriction injury model is one of the best-characterized models of neuropathic pain behavior in rats, but requires extensive time

  6. Combination of Tramadol with Minocycline Exerted Synergistic Effects on a Rat Model of Nerve Injury-Induced Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Xiao-Peng Mei

    2012-09-01

    Full Text Available Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.

  7. Costs and health resources utilization following switching to pregabalin in individuals with gabapentin-refractory neuropathic pain: a post hoc analysis.

    Science.gov (United States)

    Navarro, Ana; Saldaña, María T; Pérez, Concepción; Masramón, Xavier; Rejas, Javier

    2012-06-01

    To analyze the changes in pain severity and associated costs resulting from resource utilization and reduced productivity in patients with gabapentin-refractory peripheral neuropathic pain who switched to pregabalin therapy in primary care settings in Spain. This is a post hoc analysis of a 12-week, multicentre, noninterventional cost-of-illness study. Patients were included in the study if they were over 18 years of age and had a diagnosis of chronic, treatment-refractory peripheral neuropathic pain. The analysis included all pregabalin-naïve patients who had previously shown an inadequate response to gabapentin and switched to pregabalin. Severity of pain before and after treatment with pregabalin, alone or as an add-on therapy, was assessed using the Short-Form McGill Pain Questionnaire (SF-MPQ) and its related visual analogue scale (VA). Healthcare resource utilization, productivity (including lost-workday equivalents [LWDE]), and related costs were assessed at baseline and after pregabalin treatment. A total of 174 patients switched to pregabalin had significant and clinically relevant reductions in pain severity (mean [SD] change on SF-MPQ VA scale, -31.9 [22.1]; P use [in pregabalin add-on group], ancillary tests, and unscheduled medical visits) were observed at the end of trial. Additionally, there were substantial improvements in productivity, including a reduction in the number of LWDE following pregabalin treatment (-18.9 [26.0]; P < 0.0001). These changes correlated with substantial reductions in both direct (-652.9 ± 1622.4 €; P < 0.0001) and indirect healthcare costs (-851.6 [1259.6] €; P < 0.0001). The cost of care in patients with gabapentin-refractory peripheral neuropathic pain appeared to be significantly reduced after switching to pregabalin treatment, alone or in combination with other analgesic drugs, in a real-life setting. © 2011 The Authors. Pain Practice © 2011 World Institute of Pain.

  8. Revised definition of neuropathic pain and its grading system: an open case series illustrating its use in clinical practice.

    Science.gov (United States)

    Geber, Christian; Baumgärtner, Ulf; Schwab, Rainer; Müller, Harald; Stoeter, Peter; Dieterich, Marianne; Sommer, Clemens; Birklein, Frank; Treede, Rolf-Detlef

    2009-10-01

    The definition of neuropathic pain has recently been revised by an expert committee of the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) as "pain arising as direct consequence of a lesion or disease affecting the somatosensory system," and a grading system of "definite," "probable," and "possible" neuropathic pain has been introduced. This open case series of 5 outpatients (3 men, 2 women; mean age 48 +/- 12 years) demonstrates how the grading system can be applied, in combination with appropriate confirmatory testing, to diagnosis neuropathic conditions in clinical practice. The proposed grading system includes a dynamic algorithm that enhances the physician's ability to determine with a greater level of certainty whether a pain condition is neuropathic. Its clinical use should be further validated in prospective studies.

  9. Conditioned pain modulation: a predictor for development and treatment of neuropathic pain.

    Science.gov (United States)

    Granovsky, Yelena

    2013-09-01

    Psychophysical evaluation of endogenous pain inhibition via conditioned pain modulation (CPM) represents a new generation of laboratory tests for pain assessment. In this review we discuss recent findings on CPM in neuropathic pain and refer to psychophysical, neurophysiological, and methodological aspects of its clinical implications. Typically, chronic neuropathic pain patients express less efficient CPM, to the extent that incidence of acquiring neuropathic pain (e.g. post-surgery) and its intensity can be predicted by a pre-surgery CPM assessment. Moreover, pre-treatment CPM evaluation may assist in the correct choice of serotonin-noradrenalin reuptake inhibitor analgesic agents for individual patients. Evaluation of pain modulation capabilities can serve as a step forward in individualizing pain medicine.

  10. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    Science.gov (United States)

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  11. Long term clinical outcome of peripheral nerve stimulation in patients with chronic peripheral neuropathic pain

    DEFF Research Database (Denmark)

    Calenbergh, F. Van; Gybels, J.; Laere, K. Van

    2009-01-01

    BACKGROUND: Chronic neuropathic pain after injury to a peripheral nerve is known to be resistant to treatment. Peripheral nerve stimulation is one of the possible treatment options, which is, however, not performed frequently. In recent years we have witnessed a renewed interest for PNS. The aim...... of the present study was to evaluate the long-term clinical efficacy of PNS in a group of patients with peripheral neuropathic pain treated with PNS since the 1980s. METHODS: Of an original series of 11 patients, 5 patients could be invited for clinical examination, detailed assessment of clinical pain and QST...... functioning) also showed positive effects. Quantitative Sensory Testing results did not show significant differences in cold pain and heat pain thresholds between the "ON" and "OFF" conditions. CONCLUSION: In selected patients with peripheral neuropathic pain PNS remains effective even after more than 20...

  12. A Mangifera indica L. extract could be used to treat neuropathic pain and implication of mangiferin.

    Science.gov (United States)

    Garrido-Suárez, Bárbara B; Garrido, Gabino; Delgado, Rene; Bosch, Fe; del C Rabí, María

    2010-12-09

    It has been accepted that neuroinflammation, oxidative stress and glial activation are involved in the central sensitization underlying neuropathic pain. Vimang is an aqueous extract of Mangifera indica L. traditionally used in Cuba for its analgesic, anti-inflammatory, antioxidant and immunomodulatory properties. Several formulations are available, and also for mangiferin, its major component. Preclinical studies demonstrated that these products prevented tumor necrosis factor α -induced IκB degradation and the binding of nuclear factor κB to DNA, which induces the transcription of genes implicated in the expression of some mediators and enzymes involved in inflammation, pain, oxidative stress and synaptic plasticity. In this paper we propose its potential utility in the neuropathic pain treatment. This hypothesis is supported in the cumulus of preclinical and clinical evidence around the extract and mangiferin, its major component, and speculates about the possible mechanism of action according to recent advances in the physiopathology of neuropathic pain.

  13. A Mangifera indica L. Extract Could Be Used to Treat Neuropathic Pain and Implication of Mangiferin

    Directory of Open Access Journals (Sweden)

    María del C. Rabí

    2010-12-01

    Full Text Available It has been accepted that neuroinflammation, oxidative stress and glial activation are involved in the central sensitization underlying neuropathic pain. Vimang is an aqueous extract of Mangifera indica L. traditionally used in Cuba for its analgesic, anti-inflammatory, antioxidant and immunomodulatory properties. Several formulations are available, and also for mangiferin, its major component. Preclinical studies demonstrated that these products prevented tumor necrosis factor α -induced IκB degradation and the binding of nuclear factor κB to DNA, which induces the transcription of genes implicated in the expression of some mediators and enzymes involved in inflammation, pain, oxidative stress and synaptic plasticity. In this paper we propose its potential utility in the neuropathic pain treatment. This hypothesis is supported in the cumulus of preclinical and clinical evidence around the extract and mangiferin, its major component, and speculates about the possible mechanism of action according to recent advances in the physiopathology of neuropathic pain.

  14. Neuropathic pain in patients with spinal cord injury: report of 213 patients.

    Science.gov (United States)

    Teixeira, Manoel Jacobsen; Paiva, Wellingson Silva; Assis, Maruska Salles; Fonoff, Erich Talamoni; Bor-Seng-Shu, Edson; Cecon, Angelo Daros

    2013-09-01

    Management of neuropathic pain following spinal cord injury (SCI) can be a frustrating experience for patients since it poses a therapeutic challenge. In this article the authors describe the clinical characteristics of a group of patients with pain after spinal cord injury. In this retrospective study, 213 patients with SCI and neuropathic pain were assessed. We analyzed clinical characteristics, treatment options, and pain intensity for these patients. The main cause of SCI was spine trauma, which occurred in 169 patients, followed by tumors and infection. Complete lesions were verified in 144 patients. In our study, patients with traumatic SCI and partial lesions seem to be presented with more intense pain; however, this was not statistically significant. Neuropathic pain is a common complaint in patients with SCI and presents a treatment challenge. Knowledge of the clinical characteristics of this group of patients may help determine the best approach to intervention.

  15. Neuropathic pain in patients with spinal cord injury: report of 213 patients

    Directory of Open Access Journals (Sweden)

    Manoel Jacobsen Teixeira

    2013-09-01

    Full Text Available Objective Management of neuropathic pain following spinal cord injury (SCI can be a frustrating experience for patients since it poses a therapeutic challenge. In this article the authors describe the clinical characteristics of a group of patients with pain after spinal cord injury. Methods In this retrospective study, 213 patients with SCI and neuropathic pain were assessed. We analyzed clinical characteristics, treatment options, and pain intensity for these patients. Results The main cause of SCI was spine trauma, which occurred in 169 patients, followed by tumors and infection. Complete lesions were verified in 144 patients. In our study, patients with traumatic SCI and partial lesions seem to be presented with more intense pain; however, this was not statistically significant. Conclusions Neuropathic pain is a common complaint in patients with SCI and presents a treatment challenge. Knowledge of the clinical characteristics of this group of patients may help determine the best approach to intervention.

  16. The effect of Normast (PEA) on neuropathic pain in spinal cord injury

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Bing, Jette; Hansen, Rikke Bod Middelhede

    2015-01-01

    status: Presently, 66 patients (74% male) are included of which 55 have completed the trial. Of those included, 5% have complete tetraplegia, 39% incomplete tetraplegia, 29% complete paraplegia and 27% incomplete paraplegia. Average age at inclusion is 55.3 (±9.5) years and average time since injury is 8......Introduction: Neuropathic pain and spasticity after spinal cord injury (SCI) represent still a significant, unresolved problem causing suffering and re¬duced quality of life in patients with SCI. Treatment of neuropathic pain is a complex and difficult task, and many patients have incom......) on neuropathic pain, and sec¬ondary to study the effect of Normast on spas¬ticity and psychological functioning in patients with spinal cord injury. Population characteristics: Gender, male/female, n 43/15 Age since inclusion, years, mean (SD) 55.3 (9.5) Time since injury, years, mean (SD) 8.8 (8.9) Present...

  17. Neuropathic pain. Redefinition and a grading system for clinical and research purposes

    DEFF Research Database (Denmark)

    Treede, R.-D.; Jensen, Troels Staehelin; Campbell, J.N.

    2008-01-01

    potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pai...... evidence from a neurologic examination. This grading system is proposed for clinical and research purposes....... initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate...... activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease...

  18. Frequency, character, intensity and impact of neuropathic pain in a cohort of spinal cord injury patients

    International Nuclear Information System (INIS)

    Ullah, H.; Akhtar, N.; Matee, S.; Butt, A.W.

    2015-01-01

    The purpose of this study was to determine frequency, character, approximate location and intensity of neuropathic pain in spinal cord injury and its impact on the quality of life. Study Design: A cross-sectional survey Place and Duration of Study: Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi from Feb 2009 to Feb 2010. Material and Methods: Through non-probability convenience sampling 87 patients of both genders diagnosed with spinal cord injury based on American Spinal Injury Association criteria and admitted within a year of injury were included. Those in spinal shock, having poor cognition, inability to communicate, concurrent brain injury and history of chronic pain before injury were excluded. The history, localization and characteristics of the pain and interference with life activities were recorded. Neuropathic pain of patients was evaluated with Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale. Visual analogue scale was used to measure the severity of pain. Results: Out of 87 patients (mean age 36.9 years) seventy four were male and 13 were female. Seventy patients (80%) were AIS-A, 6 (7%) were AIS-B and 11 (13%) were AIS-C. Neuropathic pain was present in 57.5% (n=50). Most of the patients localized their pain below the neurological level of injury (78%) and rated pain intensity as moderate pain (54%). Majority (48%) described the pain as burning followed by electric shock like (42%), stabbing (8%) and pricking (2%). 48% patients reported that their quality of life was affected due to pain. 52% required two analgesics of different groups to relieve pain followed by 40% requiring three analgesics and 8% requiring one analgesic. Conclusion: Neuropathic pain is prevalent in people with spinal cord injury and adversely affects life quality. Neuropathic pain is primarily described as a burning sensation of moderate intensity mostly referred to below the neurological level of injury. (author)

  19. Learning and memory in mice with neuropathic pain: impact of old age and progranulin deficiency

    Directory of Open Access Journals (Sweden)

    Boris eAlbuquerque

    2013-11-01

    Full Text Available Persistent neuropathic pain is a frequent consequence of peripheral nerve injuries, particularly in the elderly. Using the IntelliCage we studied if a sciatic nerve injury obstructed learning and memory in young and aged mice, each in wild type and progranulin deficient mice, which develop premature signs of brain aging and are more susceptible to nerve injury evoked nociceptive hypersensitivity and hence allow to assess a potential mutual aggravation of pain and old age. Both young and aged mice developed long-term nerve injury-evoked hyperalgesia and allodynia but, in both genotypes, only aged mice with neuropathic pain showed high error rates in place avoidance acquisition tasks. Once learnt however, aged mice with neuropathic pain maintained the aversive memory longer, i.e. the extinction was significantly slowed. In addition, nerve injury in progranulin deficient mice impaired the learning of spatial sequences of awarded places, particularly in aged mice, whereas easy place preference learning was not affected by nerve injury or progranulin deficiency. The sequencing task required a discrimination of clockwise and anti-clockwise sequences and spatial flexibility to re-learn a novel sequence. The loss of spatial flexibility did not occur in sham operated mice, i.e. was a consequence of nerve injury and suggests that neuropathic pain accelerates manifestations of old age and progranulin deficiency. Neuropathic pain at old age, irrespective of the genotype, resulted in a long maintenance of aversive memory suggesting a negative alliance and possibly mutual aggravation of chronic neuropathic pain and aversive memory at old age.

  20. Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury.

    Science.gov (United States)

    Wang, Xiaoping; Li, Xiaojia; Huang, Bin; Ma, Shuai

    2016-01-01

    Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

  1. Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury.

    Science.gov (United States)

    Gaudet, Andrew D; Ayala, Monica T; Schleicher, Wolfgang E; Smith, Elana J; Bateman, Emily M; Maier, Steven F; Watkins, Linda R

    2017-09-01

    Spinal cord injury (SCI) causes chronic pain in 65% of individuals. Unfortunately, current pain management is inadequate for many SCI patients. Rodent models could help identify how SCI pain develops, explore new treatment strategies, and reveal whether acute post-SCI morphine worsens chronic pain. However, few studies explore or compare SCI-elicited neuropathic pain in rats. Here, we sought to determine how different clinically relevant contusion SCIs in male and female rats affect neuropathic pain, and whether acute morphine worsens later chronic SCI pain. First, female rats received sham surgery, or 150kDyn or 200kDyn midline T9 contusion SCI. These rats displayed modest mechanical allodynia and long-lasting thermal hyperalgesia. Next, a 150kDyn (1s dwell) midline contusion SCI was performed in male and female rats. Interestingly, males, but not females showed SCI-elicited mechanical allodynia; rats of both sexes had thermal hyperalgesia. In this model, acute morphine treatment had no significant effect on chronic neuropathic pain symptoms. Unilateral SCIs can also elicit neuropathic pain that could be exacerbated by morphine, so male rats received unilateral T13 contusion SCI (100kDyn). These rats exhibited significant, transient mechanical allodynia, but not thermal hyperalgesia. Acute morphine did not exacerbate chronic pain. Our data show that specific rat contusion SCI models cause neuropathic pain. Further, chronic neuropathic pain elicited by these contusion SCIs was not amplified by our course of early post-trauma morphine. Using clinically relevant rat models of SCI could help identify novel pain management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief

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    Tozaki-Saitoh Hidetoshi

    2009-04-01

    Full Text Available Abstract Background Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain. Results Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 μM and 1.87 μM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine. Conclusion These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part

  3. [Prevalence and characteristics of chronic pain with neuropathic component at Parakou in northern Benin in 2012].

    Science.gov (United States)

    Adoukonou, T; Gnonlonfoun, D; Kpozehouen, A; Adjien, C; Tchaou, B; Tognon-Tchegnonsi, F; Adechina, H; Covi, R; Houinato, D

    2014-11-01

    The burden of chronic and neuropathic pain is high making it an important public health problem. The epidemiology is not well known in the general population in sub-Saharan Africa. We aimed to determine the prevalence of chronic pain with a neuropathic component at Tititou in Parakou in northeastern Benin. A cross-sectional study was conducted from 1st April to 31 May 2012 and included 2314 people in a door-to-door survey. Chronic pain was defined as pain occurring for more than three months. Neuropathic pain was assessed with the DN4 score. A neurological exam was performed by a young physician for all people with chronic pain. During the interview, sociodemographic data, past medical history, weight and height were recorded. Multivariate logistic regression was performed to analyze the main associated factors. Among the 2314 people included in this survey, 49.7% were male. The mean age was 32.3 ± 13.1 years. Nine hundred seven reported pain occurring for more than 3 months. The prevalence of chronic pain was 39.2% (CI95%: 29.3-34.7). It was more frequent in females, older people, among diabetics, people with a history of any surgery, stroke, brain trauma, and alcoholism. The prevalence of chronic pain with a neuropathic component was 6.3% (CI95%: 5.0-7.9). The main associated factors were age, matrimonial status, professional occupation, body mass index, diabetes, history of zoster, history of any surgery, brain trauma. People with neuropathic pain often reported pain with burning (87.6%), prickling (82.8%), numbness (66.9%), tingling (63.4%), and lightning pain (48.3%). The main locations were the lower limbs and low back pain. This study suggested the high frequency of chronic neuropathic pain in the general population in Parakou compared with rates reported in western countries. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Dopaminergic tone does not influence pain levels during placebo interventions in patients with chronic neuropathic pain.

    Science.gov (United States)

    Skyt, Ina; Moslemi, Kurosh; Baastrup, Cathrine; Grosen, Kasper; Benedetti, Fabrizio; Petersen, Gitte L; Price, Donald D; Hall, Kathryn T; Kaptchuk, Ted J; Svensson, Peter; Jensen, Troels S; Vase, Lene

    2017-10-23

    Placebo effects have been reported in patients with chronic neuropathic pain. Expected pain levels and positive emotions are involved in the observed pain relief, but the underlying neurobiology is largely unknown. Patients with neuropathic pain are highly motivated for pain relief, and as motivational factors such as expectations of reward, as well as pain processing in itself, are related to the dopaminergic system, it can be speculated that dopamine release contributes to placebo effects in neuropathic pain. Nineteen patients with neuropathic pain after thoracic surgery were tested during a placebo intervention consisting of open and hidden applications of the pain-relieving agent lidocaine (2 mL) and no treatment. The dopamine antagonist haloperidol (2 mg) and the agonist levodopa/carbidopa (100/25 mg) were administered to test the involvement of dopamine. Expected pain levels, desire for pain relief, and ongoing and evoked pain were assessed on mechanical visual analog scales (0-10). Significant placebo effects on ongoing (P ≤ 0.003) and evoked (P ≤ 0.002) pain were observed. Expectancy and desire accounted for up to 41.2% and 71.5% of the variance in ongoing and evoked pain, respectively, after the open application of lidocaine. We found no evidence for an effect of haloperidol and levodopa/carbidopa on neuropathic pain levels (P = 0.071-0.963). Dopamine seemed to influence the levels of expectancy and desire, yet there was no evidence for indirect or interaction effects on the placebo effect. This is the first study to suggest that dopamine does not contribute to placebo effects in chronic neuropathic pain.

  5. Dynamic oscillatory signatures of central neuropathic pain in spinal cord injury.

    Science.gov (United States)

    Vuckovic, Aleksandra; Hasan, Muhammad A; Fraser, Matthew; Conway, Bernard A; Nasseroleslami, Bahman; Allan, David B

    2014-06-01

    Central neuropathic pain (CNP) is believed to be accompanied by increased activation of the sensorimotor cortex. Our knowledge of this interaction is based mainly on functional magnetic resonance imaging studies, but there is little direct evidence on how these changes manifest in terms of dynamic neuronal activity. This study reports on the presence of transient electroencephalography (EEG)-based measures of brain activity during motor imagery in spinal cord-injured patients with CNP. We analyzed dynamic EEG responses during imaginary movements of arms and legs in 3 groups of 10 volunteers each, comprising able-bodied people, paraplegic patients with CNP (lower abdomen and legs), and paraplegic patients without CNP. Paraplegic patients with CNP had increased event-related desynchronization in the theta, alpha, and beta bands (16-24 Hz) during imagination of movement of both nonpainful (arms) and painful limbs (legs). Compared to patients with CNP, paraplegics with no pain showed a much reduced power in relaxed state and reduced event-related desynchronization during imagination of movement. Understanding these complex dynamic, frequency-specific activations in CNP in the absence of nociceptive stimuli could inform the design of interventional therapies for patients with CNP and possibly further understanding of the mechanisms involved. This study compares the EEG activity of spinal cord-injured patients with CNP to that of spinal cord-injured patients with no pain and also to that of able-bodied people. The study shows that the presence of CNP itself leads to frequency-specific EEG signatures that could be used to monitor CNP and inform neuromodulatory treatments of this type of pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.

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    Matthew Thakur

    Full Text Available Joint degeneration observed in the rat monoiodoacetate (MIA model of osteoarthritis shares many histological features with the clinical condition. The accompanying pain phenotype has seen the model widely used to investigate the pathophysiology of osteoarthritis pain, and for preclinical screening of analgesic compounds. We have investigated the pathophysiological sequellae of MIA used at low (1 mg or high (2 mg dose. Intra-articular 2 mg MIA induced expression of ATF-3, a sensitive marker for peripheral neuron stress/injury, in small and large diameter DRG cell profiles principally at levels L4 and 5 (levels predominated by neurones innervating the hindpaw rather than L3. At the 7 day timepoint, ATF-3 signal was significantly smaller in 1 mg MIA treated animals than in the 2 mg treated group. 2 mg, but not 1 mg, intra-articular MIA was also associated with a significant reduction in intra-epidermal nerve fibre density in plantar hindpaw skin, and produced spinal cord dorsal and ventral horn microgliosis. The 2 mg treatment evoked mechanical pain-related hypersensitivity of the hindpaw that was significantly greater than the 1 mg treatment. MIA treatment produced weight bearing asymmetry and cold hypersensitivity which was similar at both doses. Additionally, while pregabalin significantly reduced deep dorsal horn evoked neuronal responses in animals treated with 2 mg MIA, this effect was much reduced or absent in the 1 mg or sham treated groups. These data demonstrate that intra-articular 2 mg MIA not only produces joint degeneration, but also evokes significant axonal injury to DRG cells including those innervating targets outside of the knee joint such as hindpaw skin. This significant neuropathic component needs to be taken into account when interpreting studies using this model, particularly at doses greater than 1 mg MIA.

  7. Patients' Experience of therapeutic footwear whilst living at risk of neuropathic diabetic foot ulceration: an interpretative phenomenological analysis (IPA).

    Science.gov (United States)

    Paton, Joanne S; Roberts, Anne; Bruce, Graham K; Marsden, Jonathan

    2014-02-22

    Previous work has found that people with diabetes do not wear their therapeutic footwear as directed, but the thinking behind this behaviour is unclear. Adherence to therapeutic footwear advice must improve in order to reduce foot ulceration and amputation risk in people with diabetes and neuropathy. Therefore this study aimed to explore the psychological influences and personal experiences behind the daily footwear selection of individuals with diabetes and neuropathy. An interpretative phenomenological analysis (IPA) approach was used to explore the understanding and experience of therapeutic footwear use in people living at risk of diabetic neuropathic foot ulceration. This study benefited from the purposive selection of a small sample of four people and used in-depth semi structured interviews because it facilitated the deep and detailed examination of personal thoughts and feelings behind footwear selection. Four overlapping themes that interact to regulate footwear choice emerged from the analyses: a) Self-perception dilemma; resolving the balance of risk experienced by people with diabetes and neuropathy day to day, between choosing to wear footwear to look and feel normal and choosing footwear to protect their feet from foot ulceration; b) Reflective adaption; The modification and individualisation of a set of values about footwear usage created in the minds of people with diabetes and neuropathy; c) Adherence response; The realignment of footwear choice with personal values, to reinforce the decision not to change behaviour or bring about increased footwear adherence, with or without appearance management; d) Reality appraisal; A here and now appraisal of the personal benefit of footwear choice on emotional and physical wellbeing, with additional consideration to the preservation of therapeutic footwear. For some people living at risk of diabetic neuropathic foot ulceration, the decision whether or not to wear therapeutic footwear is driven by the

  8. Bortezomib induces neuropathic pain through protein kinase C-mediated activation of presynaptic NMDA receptors in the spinal cord.

    Science.gov (United States)

    Xie, Jing-Dun; Chen, Shao-Rui; Chen, Hong; Pan, Hui-Lin

    2017-09-01

    Chemotherapeutic drugs, including bortezomib, often cause painful peripheral neuropathy, which is a severe dose-limiting adverse effect experienced by many cancer patients. The glutamate N-methyl-d-aspartate receptors (NMDARs) at the spinal cord level are critically involved in the synaptic plasticity associated with neuropathic pain. In this study, we determined whether treatment with bortezomib, a proteasome inhibitor, affects the NMDAR activity of spinal dorsal horn neurons. Systemic treatment with bortezomib in rats did not significantly affect postsynaptic NMDAR currents elicited by puff application of NMDA directly to dorsal horn neurons. Bortezomib treatment markedly increased the baseline frequency of miniature excitatory postsynaptic currents (EPSCs), which was completely normalized by the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5). AP5 also reduced the amplitude of monosynaptic EPSCs evoked by dorsal root stimulation in bortezomib-treated, but not vehicle-treated, rats. Furthermore, inhibition of protein kinase C (PKC) with chelerythrine fully reversed the increased frequency of miniature EPSCs and the amplitude of evoked EPSCs in bortezomib-treated rats. Intrathecal injection of AP5 and chelerythrine both profoundly attenuated mechanical allodynia and hyperalgesia induced by systemic treatment with bortezomib. In addition, treatment with bortezomib induced striking membrane translocation of PKC-βII, PKC-δ, and PKC-ε in the dorsal root ganglion. Our findings indicate that bortezomib treatment potentiates nociceptive input from primary afferent nerves via PKC-mediated tonic activation of presynaptic NMDARs. Targeting presynaptic NMDARs and PKC at the spinal cord level may be an effective strategy for treating chemotherapy-induced neuropathic pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Upregulation of neuronal kynurenine 3-monooxygenase mediates depression-like behavior in a mouse model of neuropathic pain.

    Science.gov (United States)

    Laumet, Geoffroy; Zhou, Wenjun; Dantzer, Robert; Edralin, Jules D; Huo, XiaoJiao; Budac, David P; O'Connor, Jason C; Lee, Anna W; Heijnen, Cobi J; Kavelaars, Annemieke

    2017-11-01

    Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain interleukin (IL)-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain. The SNI-induced increase of Kmo mRNA was associated with increased KMO protein and elevated quinolinic acid and reduced kynurenic acid in the contralateral hippocampus. The increase in KMO-protein in response to SNI mostly took place in hippocampal NeuN-positive neurons rather than microglia. Inhibition of brain IL-1 signaling by intracerebroventricular administration of IL-1 receptor antagonist after SNI prevented the increase in Kmo mRNA and depression-like behavior measured by forced swim test. However, inhibition of brain IL-1 signaling has no effect on mechanical allodynia. In addition, intracerebroventricular administration of the KMO inhibitor Ro 61-8048 abrogated depression-like behavior without affecting mechanical allodynia after SNI. We show for the first time that the development of depression-like behavior in the SNI model requires brain IL-1 signaling and activation of neuronal KMO, while pain is independent of this pathway. Inhibition of KMO may represent a promising target for treating depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Delta-opioid receptor analgesia is independent of microglial activation in a rat model of neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Joanna Mika

    Full Text Available The analgesic effect of delta-opioid receptor (DOR ligands in neuropathic pain is not diminished in contrast to other opioid receptor ligands, which lose their effectiveness as analgesics. In this study, we examine whether this effect is related to nerve injury-induced microglial activation. We therefore investigated the influence of minocycline-induced inhibition of microglial activation on the analgesic effects of opioid receptor agonists: morphine, DAMGO, U50,488H, DPDPE, Deltorphin II and SNC80 after chronic constriction injury (CCI to the sciatic nerve in rats. Pre-emptive and repeated administration of minocycline (30 mg/kg, i.p. over 7 days significantly reduced allodynia and hyperalgesia as measured on day 7 after CCI. The antiallodynic and antihyperalgesic effects of intrathecally (i.t. administered morphine (10-20 µg, DAMGO (1-2 µg and U50,488H (25-50 µg were significantly potentiated in rats after minocycline, but no such changes were observed after DPDPE (10-20 µg, deltorphin II (1.5-15 µg and SNC80 (10-20 µg administration. Additionally, nerve injury-induced down-regulation of all types of opioid receptors in the spinal cord and dorsal root ganglia was not influenced by minocycline, which indicates that the effects of opioid ligands are dependent on other changes, presumably neuroimmune interactions. Our study of rat primary microglial cell culture using qRT-PCR, Western blotting and immunocytochemistry confirmed the presence of mu-opioid receptors (MOR and kappa-opioid receptors (KOR, further we provide the first evidence for the lack of DOR on microglial cells. In summary, DOR analgesia is different from analgesia induced by MOR and KOR receptors because it does not dependent on injury-induced microglial activation. DOR agonists appear to be the best candidates for new drugs to treat neuropathic pain.

  11. Patients’ Experience of therapeutic footwear whilst living at risk of neuropathic diabetic foot ulceration: an interpretative phenomenological analysis (IPA)

    Science.gov (United States)

    2014-01-01

    Background Previous work has found that people with diabetes do not wear their therapeutic footwear as directed, but the thinking behind this behaviour is unclear. Adherence to therapeutic footwear advice must improve in order to reduce foot ulceration and amputation risk in people with diabetes and neuropathy. Therefore this study aimed to explore the psychological influences and personal experiences behind the daily footwear selection of individuals with diabetes and neuropathy. Methods An interpretative phenomenological analysis (IPA) approach was used to explore the understanding and experience of therapeutic footwear use in people living at risk of diabetic neuropathic foot ulceration. This study benefited from the purposive selection of a small sample of four people and used in-depth semi structured interviews because it facilitated the deep and detailed examination of personal thoughts and feelings behind footwear selection. Findings Four overlapping themes that interact to regulate footwear choice emerged from the analyses: a) Self-perception dilemma; resolving the balance of risk experienced by people with diabetes and neuropathy day to day, between choosing to wear footwear to look and feel normal and choosing footwear to protect their feet from foot ulceration; b) Reflective adaption; The modification and individualisation of a set of values about footwear usage created in the minds of people with diabetes and neuropathy; c) Adherence response; The realignment of footwear choice with personal values, to reinforce the decision not to change behaviour or bring about increased footwear adherence, with or without appearance management; d) Reality appraisal; A here and now appraisal of the personal benefit of footwear choice on emotional and physical wellbeing, with additional consideration to the preservation of therapeutic footwear. Conclusion For some people living at risk of diabetic neuropathic foot ulceration, the decision whether or not to wear

  12. How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.

    Science.gov (United States)

    La Cesa, S; Tamburin, S; Tugnoli, V; Sandrini, G; Paolucci, S; Lacerenza, M; Marchettini, P; Cruccu, G; Truini, A

    2015-12-01

    Patients with peripheral and central nervous system diseases may suffer from different types of pain, namely nociceptive, neuropathic and mixed pain. Although in some cases, the distinction between these types of pain is clinically evident, yet in some patients an accurate differential diagnosis requires dedicated clinical examination, screening questionnaires and diagnostic techniques some of which are available only in specialized pain centres. This review briefly addresses the currently agreed definitions of the different types of pain and shows how clinical examination, pain questionnaires and diagnostic tests can help the clinicians in identifying neuropathic pain.

  13. Bioinformatic Analysis of Potential Biomarkers for Spinal Cord Injured Patients With Intractable Neuropathic Pain.

    Science.gov (United States)

    Wang, Yimin; Ye, Fang; Huang, Chanyan; Xue, Faling; Li, Yingyuan; Gao, Shaowei; Qiu, Zeting; Li, Si; Chen, Qinchang; Zhou, Huaqiang; Song, Yiyan; Huang, Wenqi; Tan, Wulin; Wang, Zhongxing

    2018-03-15

    Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting patients' life quality. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and MicroRNAs(miRNAs) related to neuropathic pain by bioinformatics method. Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from patients with or without neuropathic pain after spinal cord injury (SCI) were collected. 12 samples with neuropathic pain and 13 samples without pain as control were included in the downloaded microarray. Differentially expressed genes (DEGs) between neuropathic pain group and control group were detected using GEO2R online tool. Functional enrichment analysis of DEGs was performed using DAVID database. Protein-protein interaction (PPI) network was constructed from STRING database. MiRNAs targeting these DEGs were obtained from miRNet database. A merged miRNA-DEG network was constructed and analyzed with Cytoscape software. Total 1134 DEGs were identified between patients with or without neuropathic pain(case and control) and 454 biological processes were enriched. We identified 4 targeted miRNAs, including mir-204-5p, mir-519d-3p, mir-20b-5p, mir-6838-5p, which may be the potential biomarker for SCI patients. Protein modification and regulation biological process of central nervous system may be a risk factor of in SCI patients. Certain genes and miRNAs may be potential biomarkers for the prediction of and potential targets for prevention and treatment of neuropathic pain after SCI.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http

  14. Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study

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    Schaefer C

    2014-10-01

    Full Text Available Caroline Schaefer,1 Alesia Sadosky,2 Rachael Mann,3 Shoshana Daniel,4 Bruce Parsons,2 Michael Tuchman,5 Alan Anschel,6 Brett R Stacey,7 Srinivas Nalamachu,8 Edward Nieshoff9 1Covance Market Access Services Inc., Gaithersburg, MD, 2Pfizer, Inc., New York, NY, 3Covance Market Access Services Inc., San Diego, CA, 4Covance Market Access Services Inc., Conshohocken, PA, 5Palm Beach Neurological Center, Palm Beach Gardens, FL, 6Rehabilitation Institute of Chicago, Chicago, IL, 7Oregon Health and Science University, Portland, OR, 8International Clinical Research Institute, Overland Park, KS, 9Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, USABackground: As with many chronic conditions, patients with neuropathic pain (NeP are high consumers of health care resources. However, limited literature exists on the economic burden of NeP, including its impact on productivity. The aim of this study was to characterize health care resource utilization, productivity, and costs associated with NeP by pain severity level in US adults.Methods: Subjects (n=624 with painful diabetic peripheral neuropathy, human immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP, spinal cord injury with NeP, chronic low back pain with NeP, and small fiber neuropathy were recruited during routine office visits to US community-based general practitioners and specialists. Clinicians captured clinical characteristics, NeP-related medications, and health care resource utilization based on 6-month retrospective medical chart review. Subjects completed questionnaires on demographics, pain/symptoms, costs, and productivity. Brief Pain Inventory pain severity scores were used to classify subjects by mild, moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates were estimated, and differences across pain severity groups were evaluated.Results: In total, 624 subjects were recruited (mean age 55.5±13.7 years; 55.4% male

  15. Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain.

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    Shigeo Hasegawa

    Full Text Available BACKGROUND: Neuropathic pain is a highly debilitating chronic pain following damage to peripheral sensory neurons and is often resistant to all treatments currently available, including opioids. We have previously shown that peripheral nerve injury induces activation of cytosolic phospholipase A(2 (cPLA(2 in injured dorsal root ganglion (DRG neurons that contribute to tactile allodynia, a hallmark of neuropathic pain. However, lipid mediators downstream of cPLA(2 activation to produce tactile allodynia remain to be determined. PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha (TNFalpha and interleukin-1beta (IL-1beta expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naïve rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS: Our results indicate that the PAF/PAFR system has an important role in production of TNFalpha and IL-1beta in the DRG and tactile allodynia following peripheral nerve injury and suggest that blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain.

  16. The use of 10-kilohertz spinal cord stimulation in a cohort of patients with chronic neuropathic limb pain refractory to medical management.

    Science.gov (United States)

    Al-Kaisy, Adnan; Palmisani, Stefano; Smith, Tom; Harris, Stephany; Pang, David

    2015-01-01

    It is the purpose of this study to document our experience with the use of a 10-kHz high-frequency spinal cord stimulation (SCS) device for the relief of neuropathic pain of the upper and lower limbs. A retrospective chart review was performed of all patients treated with the 10-kHz high-frequency SCS system for neuropathic pain (upper or lower limb) refractory to conventional treatment. All patients underwent a trial with one or two eight-contact percutaneous leads using 50-Hz traditional stimulation. If ≥ 80% paresthesia coverage of the painful area with traditional SCS was obtained, high-frequency 10-kHz SCS was used. Patients who had a significant reduction in pain score (≥ 50%) at the end of the trial received a permanent implant and were then followed for up to six months. Outcome measures included a numeric rating scale for pain, the Brief Pain Inventory, health-related quality of life (EQ-5D), the Pain Catastrophizing Scale, and patient satisfaction. Fifteen patients completed a trial of high-frequency 10-kHz SCS. Eleven patients proceeded to permanent implantation. Ten of the 11 patients who proceeded to full implantation had significant reductions in all of the collected outcome variables at one, three, and six months. In this small cohort of patients, high-frequency 10-kHz SCS reduced pain and improved quality of life. However, before we can conclude that high-frequency 10-kHz SCS for neuropathic pain of the upper and lower extremities is efficacious, a large-scale multicenter observational study should be performed to corroborate our small retrospective study. © 2014 International Neuromodulation Society.

  17. P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2',3'-dideoxycytidine.

    Science.gov (United States)

    Yi, Zhihua; Xie, Lihui; Zhou, Congfa; Yuan, Huilong; Ouyang, Shuai; Fang, Zhi; Zhao, Shanhong; Jia, Tianyu; Zou, Lifang; Wang, Shouyu; Xue, Yun; Wu, Bing; Gao, Yun; Li, Guilin; Liu, Shuangmei; Xu, Hong; Xu, Changshui; Zhang, Chunping; Liang, Shangdong

    2018-03-01

    The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y 12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y 12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIV-gp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y 12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca 2+ ] i activated by the P2Y 12 receptor agonist 2-(Methylthio) adenosine 5'-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y 12 receptor shRNA treatment inhibited 2-MeSADP-induced [Ca 2+ ] i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y 12 receptor in DRG SGCs reduced the release of pro-inflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y 12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

  18. Pain from Dental Implant Placement, Inflammatory Pulpitis Pain, and Neuropathic Pain Present Different Somatosensory Profiles.

    Science.gov (United States)

    Porporatti, André Luís; Bonjardim, Leonardo Rigoldi; Stuginski-Barbosa, Juliana; Bonfante, Estevam Augusto; Costa, Yuri Martins; Rodrigues Conti, Paulo César

    2017-01-01

    To address the two following questions: (1) What kind of somatosensory abnormalities may be characterized in patients receiving dental implants (IMP), in ongoing inflammatory dental pulpitis (IP) patients, and in neuropathic pain (atypical odontalgia [AO]) patients? and (2) What sort of sensory and neural changes may result from dental implant placement surgery and pulpectomy? A total of 60 subjects were divided into three groups: the IMP (n = 20), IP (n = 20), and AO groups (n = 20). Quantitative sensory testing (QST) was performed preoperatively (baseline) for all three groups and postoperatively at 1 month and 3 months after dental implant placement or pulpectomy (in the IMP group and IP group, respectively). Statistical analyses were completed with one-way and two-way analysis of variance and z score transformations (α = 5%). The main findings of this study indicated that: (1) Elevations in mechanical detection threshold (MDT) and in current perception threshold (CPT) related to C-fiber activation, indicating a loss of function, were found at baseline in IP patients; (2) Somatosensory abnormalities such as allodynia, reduced MDT and mechanical pain threshold (MPT), and impaired pain modulation were found in AO patients; (3) No somatosensory alterations after implant placement were found in the IMP group; and (4) Somatosensory alterations in the form of reduction in the CPT related to C-fiber activation were reported 3 months after pulpectomy in the IP group. This study showed that somatosensory abnormalities were evident in AO and IP patients, and somatosensory alterations were seen in IP patients even 3 months after pulpectomy. However, no somatosensory alterations were seen after implant placement.

  19. Dynamic Changes in Nociception and Pain Perception After Spinal Cord Stimulation in Chronic Neuropathic Pain Patients.

    Science.gov (United States)

    Biurrun Manresa, José A; Sörensen, Jan; Andersen, Ole K; Arendt-Nielsen, Lars; Gerdle, Björn

    2015-12-01

    Patients with an implanted spinal cord stimulation (SCS) system for pain management present an opportunity to study dynamic changes in the pain system in a situation where patients are not stimulated (ie, experiencing severe pain) compared with a situation in which patients have just been stimulated (ie, pain free or greatly reduced pain). The aims of this study were (1) to determine if there are differences in nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) before and after SCS; and (2) to establish if these differences are related to psychological factors associated with chronic pain. Seventeen volunteers with chronic neuropathic pain participated in the experiment. Electrical stimuli were applied to assess the NWR-T and the EP-T. In addition, psychological factors (ie, pain characteristics, depression, anxiety, and disability indexes) were also recorded. The NWR-T and EP-T were assessed with the SCS system off (at least 8 h before the experiment), and then reassessed 1 hour after the SCS system was turned on. Ongoing pain intensity ratings decreased (P=0.018), whereas the NWR-T increased (P=0.028) after the SCS was turned on, whereas no significant difference was found for EP-T (P=0.324). Psychological factors were significant predictors for EP-T but not for NWR-T. The results of this study suggest that pain relief after SCS is partially mediated by a decrease in the excitability of dorsal horn neurons in the spinal cord.

  20. Evaluation and Optimization of Therapeutic Footwear for Neuropathic Diabetic Foot Patients Using In-Shoe Plantar Pressure Analysis

    Science.gov (United States)

    Bus, Sicco A.; Haspels, Rob; Busch-Westbroek, Tessa E.

    2011-01-01

    OBJECTIVE Therapeutic footwear for diabetic foot patients aims to reduce the risk of ulceration by relieving mechanical pressure on the foot. However, footwear efficacy is generally not assessed in clinical practice. The purpose of this study was to assess the value of in-shoe plantar pressure analysis to evaluate and optimize the pressure-reducing effects of diabetic therapeutic footwear. RESEARCH DESIGN AND METHODS Dynamic in-shoe plantar pressure distribution was measured in 23 neuropathic diabetic foot patients wearing fully customized footwear. Regions of interest (with peak pressure >200 kPa) were selected and targeted for pressure optimization by modifying the shoe or insole. After each of a maximum of three rounds of modifications, the effect on in-shoe plantar pressure was measured. Successful optimization was achieved with a peak pressure reduction of >25% (criterion A) or below an absolute level of 200 kPa (criterion B). RESULTS In 35 defined regions, mean peak pressure was significantly reduced from 303 (SD 77) to 208 (46) kPa after an average 1.6 rounds of footwear modifications (P diabetic foot. This result provides an objective approach to instantly improve footwear quality, which should reduce the risk for pressure-related plantar foot ulcers. PMID:21610125

  1. Topical Ketamine 10% for Neuropathic Pain in Spinal Cord Injury Patients: An Open-Label Trial.

    Science.gov (United States)

    Rabi, Joseph; Minori, Joshua; Abad, Hasan; Lee, Ray; Gittler, Michelle

    2016-01-01

    Topical ketamine, an N-methyl-D-aspartate antagonist, has been shown to be effective in certain neuropathic pain syndromes. The objective of this study was to determine the efficacy of topical ketamine in spinal cord injury patients with neuropathic pain. An open label trial enrolled five subjects at an outpatient rehabilitation hospital with traumatic spinal cord injuries who had neuropathic pain at or below the level of injury. Subjects applied topical ketamine 10% three times a day for a two-week duration. Subjects recorded their numerical pain score-ranging from 0 to 10, with 0 representing "no pain, 5 representing "moderate pain," and 10 being described as "worst possible pain"-in a journal at the time of application of topical ketamine and one hour after application. Using a numerical pain scale allows for something as subjective as pain to be given an objective quantification. Subjects also recorded any occurrence of adverse events and level of satisfaction. All five subjects had a decrease in their numerical pain scale by the end of two weeks, ranging from 14% to 63%. The duration ranged from one hour in one subject to the next application in other subjects. There were no adverse effects. Overall, four out of the five subjects stated they were satisfied. Topical ketamine 10% is an effective neuropathic pain medicine in patients with spinal cord injuries; however, further studies need to be done with a placebo and larger sample size. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  2. Neuropathic pain and its treatment with ARA 290 and ketamine : overlapping pathways

    NARCIS (Netherlands)

    Swartjes, Maarten

    2014-01-01

    Neuropathic pain is a disabling disease with a mechanism consisting of several pathways that ultimately converge in the development and persistence tactile and cold allodynia. Pharmacological treatment is often inadequate and coincides with intolerable side effects. The spared nerve injury animal

  3. Exploring the potential effect of Ocimum sanctum in vincristine-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    Jaggi Amteshwar

    2010-01-01

    Full Text Available Abstract The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in vincristine-induced peripheral neuropathic pain in rats. Peripheral neuropathy was induced in rats by administration of vincristine sulfate (50 μg/kg i.p. for 10 consecutive days. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species (TBARS, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Vincristine administration was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia. Furthermore, vincristine administration was also associated with an increase in oxidative stress and calcium levels. However, administration of Ocimum sanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated vincristine-induced neuropathic pain along with decrease in oxidative stress and calcium levels. It may be concluded that Ocimum sanctum has ameliorative potential in attenuating chemotherapy induced-painful neuropathic state, which may be attributed to decrease in oxidative stress and calcium levels. Furthermore, saponin rich fraction of Ocimum sanctum may be responsible for its noted beneficial effect in neuropathic pain in rats.

  4. Pain management strategies for neuropathic pain in Fabry disease--a systematic review

    NARCIS (Netherlands)

    Schuller, Y.; Linthorst, G. E.; Hollak, C. E. M.; van Schaik, I. N.; Biegstraaten, M.

    2016-01-01

    Neuropathic pain is one of the key features of (classical) Fabry disease (FD). No randomized clinical trials comparing effectiveness of different pain management strategies have been performed. This review aims to give an overview of existing pain management strategies. PubMed and Embase were

  5. Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.

    NARCIS (Netherlands)

    Bleeker, C.P.; Bremer, R.; Dongelmans, D.A.; Dongen, R.T.M. van; Crul, B.J.P.

    2001-01-01

    Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58-year-old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 microg/h resulting in fentanyl plasma levels of

  6. Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

    Science.gov (United States)

    Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

    2017-01-01

    Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Prevalence, Causes, and Treatment of Neuropathic Pain in Dutch Nursing Home Residents : A Retrospective Chart Review

    NARCIS (Netherlands)

    van Kollenburg, Esther G. P.; Lavrijsen, Jan C. M.; Verhagen, Stans C.; Zuidema, Sytse U.; Schalkwijk, Annelies; Vissers, Kris C. P.

    Objectives To identify the prevalence and causes of neuropathic pain in Dutch nursing home residents; to establish the prevalence of painful and nonpainful diabetic polyneuropathy in a subsample of individuals with diabetes mellitus and central poststroke pain (CPSP) in a subsample of individuals

  8. α2δ Modulators for management of compression neuropathic pain: A review of three case series

    Directory of Open Access Journals (Sweden)

    Tariq A Tramboo

    2009-01-01

    Conclusion: These results indicate the effectiveness of a2d modulators for management of neuropathic pain secondary to compression radiculopathy. The results also suggest a possible therapeutic superiority of LYRICA over locally available generic brands of pregabalin and gabapentin. These findings need to be further examined in randomized, controlled trials.

  9. Dynamics of circadian thalamocortical flow of information during a peripheral neuropathic pain condition

    Directory of Open Access Journals (Sweden)

    Helder eCardoso-Cruz

    2011-08-01

    Full Text Available It is known that the thalamocortical loop plays a crucial role in the encoding of sensory-discriminative features of painful stimuli. However, only a few studies have addressed the changes in thalamocortical dynamics that may occur after the onset of chronic pain. Our goal was to evaluate how the induction of chronic neuropathic pain affected the flow of information within the thalamocortical loop throughout the brain states of the sleep-wake cycle. To address this issue we recorded local field potentials – LFPs – both before and after the establishment of neuropathic pain in awake freely moving adult rats chronically implanted with arrays of multielectrodes in the lateral thalamus and primary somatosensory cortex. Our results show that the neuropathic injury induced changes in the number of wake and slow-wave-sleep state episodes, and especially in the total number of transitions between brain states. Moreover, partial directed coherence – PDC – analysis revealed that the amount of information flow between cortex and thalamus in neuropathic animals decreased significantly, indicating that the overall thalamic activity had less weight over the cortical activity. However, thalamocortical LFPs displayed higher phase-locking during awake and slow-wave-sleep episodes after the nerve lesion, suggesting faster transmission of relevant information along the thalamocortical loop. The observed changes are in agreement with the hypothesis of thalamic dysfunction after the onset of chronic pain, and may result from diminished inhibitory effect of the primary somatosensory cortex over the lateral thalamus.

  10. Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.

    Science.gov (United States)

    Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

    2017-09-01

    Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron-glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

  11. Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: modulation by hippocampal sigma receptors.

    Science.gov (United States)

    Kotagale, Nandkishor Ramdas; Shirbhate, Saurabh Haridas; Shukla, Pradeep; Ugale, Rajesh Ramesh

    2013-08-15

    Present study investigated the influence of the sigma (σ₁ and σ₂) receptors within hippocampus on the agmatine induced antinociception in neuropathic rats. Animals were subjected to sciatic nerve ligation for induction of neuropathic pain and observed the paw withdrawal latency in response to thermal hyperalgesia, cold allodynia and the mechanical hyperalgesia. Intrahippocampal (i.h.) as well as intraperitoneal (i.p.) administration of agmatine attenuated neuropathic pain in sciatic nerve ligated rats. Intrahippocampal administration of σ₁ agonist (+)-pentazocine or σ₂ agonist PB28 sensitized whereas, σ₁ antagonist BD1063 or σ₂ antagonist SM21 potentiated antinociceptive effect of agmatine. The behavioral effects correlated with hippocampal tumor necrosis factor-α (TNF-α) levels observed by western blot analysis. These results suggest that both the σ₁ and σ₂ receptor subunits within hippocampus play an important role in antinociceptive action of agmatine against neuropathic pain. © 2013 Elsevier B.V. All rights reserved.

  12. Aromatherapy Massage for Neuropathic Pain and Quality of Life in Diabetic Patients.

    Science.gov (United States)

    Gok Metin, Zehra; Arikan Donmez, Ayse; Izgu, Nur; Ozdemir, Leyla; Arslan, Ismail Emre

    2017-07-01

    This study aimed to examine the effects of aromatherapy massage on neuropathic pain severity and quality of life (QoL) in patients suffering from painful diabetic neuropathy. This open-label randomized controlled clinical study was conducted in a university hospital endocrine outpatient clinic in Turkey. The study sample consisted of 46 patients, randomly allocated to an intervention group (n = 21) and a control group (n = 25). The intervention group received aromatherapy massage three times per week for a period of 4 weeks. The control group received only routine care. Data were collected from patients using the Douleur Neuropathique questionnaire, the visual analog scale, and the Neuropathic Pain Impact on Quality of Life questionnaire. Neuropathic pain scores significantly decreased in the intervention group compared with the control group in the fourth week of the study. Similarly, QoL scores significantly improved in the intervention group in the fourth week of the study. Aromatherapy massage is a simple and effective nonpharmacological nursing intervention that can be used to manage neuropathic pain and improve QoL in patients with painful neuropathy. Aromatherapy massage is a well-tolerated, feasible, and safe nonpharmacological method that can be readily integrated into clinical settings by nursing staff. The essential oils rosemary, geranium, lavender, eucalyptus, and chamomile can be safely used by nurses in the clinical setting, if applicable. However, training and experience of nurses in aromatherapy massage is critical to achieving positive results. © 2017 Sigma Theta Tau International.

  13. Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain

    NARCIS (Netherlands)

    Lefaucheur, Jean-Pascal; Holsheimer, J.; Goujon, Colette; Keravel, Yves; Nguyen, Jean-Paul

    Epidural motor cortex stimulation (EMCS) is a therapeutic option for chronic, drug-resistant neuropathic pain, but its mechanisms of action remain poorly understood. In two patients with refractory hand pain successfully treated by EMCS, the presence of implanted epidural cervical electrodes for

  14. Ultramicronized Palmitoylethanolamide (PEA) in spinal cord injury neuropathic pain: a randomized controlled trial

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Bing, Jette; Hansen, Rikke Bod Middelhede

    2015-01-01

    . Methods  A randomized, double-blind, placebo-controlled parallel multicenter study. Study population of at least 66 patients must complete the 12 week trial.Questionnaires regarding neuropathic pain, spasticity, insomnia, anxiety and depression are completed before and after treatment. A numeric...

  15. Delphi process yielded consensus on terminology and research agenda for therapeutic footwear for neuropathic foot.

    NARCIS (Netherlands)

    Dahmen, R.; van der Wilden, G.J.; Lankhorst, G.J.; Boers, M.

    2008-01-01

    Objective: To investigate areas of consensus and disagreement among Dutch physiatrists concerning prescription of therapeutic footwear for the neuropathic foot and to develop a research agenda. Study Design and Setting: Forty participants were physiatrists and experts in the field of orthopedic shoe

  16. Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system

    Science.gov (United States)

    Zhao, Xin; Wang, Chuang; Cui, Wu-Geng; Ma, Qing; Zhou, Wen-Hua

    2015-01-01

    Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain. PMID:25761874

  17. Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults.

    Science.gov (United States)

    Wiffen, Philip J; Knaggs, Roger; Derry, Sheena; Cole, Peter; Phillips, Tudor; Moore, R Andrew

    2016-12-27

    Paracetamol, either alone or in combination with codeine or dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double-blind studies. To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries. We included randomised, double-blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or dihydrocodeine, with placebo or another active treatment in chronic neuropathic pain. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE. No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect. There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.

  18. Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.

    Science.gov (United States)

    Taha, Omneya; Opitz, Thoralf; Mueller, Marcus; Pitsch, Julika; Becker, Albert; Evert, Bernd Oliver; Beck, Heinz; Jeub, Monika

    2017-11-01

    Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the somata of nociceptive fibers, in a rat model of GBS (experimental autoimmune neuritis=EAN). EAN rats developed behavioral signs of neuropathic pain. This was accompanied by a significant shortening of action potentials due to a more rapid repolarization and an increase in repetitive firing in a subgroup of capsaicin-responsive DRG neurons. Na + current measurements revealed a significant increase of the fast TTX-sensitive current and a reduction of the persistent TTX-sensitive current component. These changes of Na + currents may account for the significant decrease in AP duration leading to an overall increase in excitability and are therefore possibly directly linked to pathological pain behavior. Thus, like in other animal models of neuropathic and inflammatory pain, Na + channels seem to be crucially involved in the pathology of GBS and may constitute promising targets for pain modulating pharmaceuticals. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Differential transcriptional profiling of damaged and intact adjacent dorsal root ganglia neurons in neuropathic pain.

    Directory of Open Access Journals (Sweden)

    A K Reinhold

    Full Text Available Neuropathic pain, caused by a lesion in the somatosensory system, is a severely impairing mostly chronic disease. While its underlying molecular mechanisms are not thoroughly understood, neuroimmune interactions as well as changes in the pain pathway such as sensitization of nociceptors have been implicated. It has been shown that not only are different cell types involved in generation and maintenance of neuropathic pain, like neurons, immune and glial cells, but, also, intact adjacent neurons are relevant to the process. Here, we describe an experimental approach to discriminate damaged from intact adjacent neurons in the same dorsal root ganglion (DRG using differential fluorescent neuronal labelling and fluorescence-activated cell sorting (FACS. Two fluorescent tracers, Fluoroemerald (FE and 1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI, were used, whose properties allow us to distinguish between damaged and intact neurons. Subsequent sorting permitted transcriptional analysis of both groups. Results and qPCR validation show a strong regulation in damaged neurons versus contralateral controls as well as a moderate regulation in adjacent neurons. Data for damaged neurons reveal an mRNA expression pattern consistent with established upregulated genes like galanin, which supports our approach. Moreover, novel genes were found strongly regulated such as corticotropin-releasing hormone (CRH, providing novel targets for further research. Differential fluorescent neuronal labelling and sorting allows for a clear distinction between primarily damaged neuropathic neurons and "bystanders," thereby facilitating a more detailed understanding of their respective roles in neuropathic processes in the DRG.

  20. The Impact of Enrollment in a Specialized Interdisciplinary Neuropathic Pain Clinic

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    Alex Garven

    2011-01-01

    Full Text Available BACKGROUND: Chronic pain clinics have been created because of the increasing recognition of chronic pain as a very common, debilitating condition that requires specialized care. Neuropathic pain (NeP is a multifaceted, specialized form of chronic pain that often requires input from multiple disciplines for assessment and management.

  1. Neuropathic Pain Mechanisms in Patients with Chronic Sports Injuries : A Diagnostic Model Useful in Sports Medicine?

    NARCIS (Netherlands)

    van Wilgen, Cornelis P.; Keizer, Doeke

    2011-01-01

    Objective. The pathophysiology of chronic sports injuries such as overuse or tendinopathy remains largely unknown. With this exploratory study, we aim to detect signs of sensitization of the nervous system. Sensitization is an indication of the involvement of neuropathic mechanisms in patients with

  2. Decompression with the aid of insoles in the treatment of diabetic neuropathic ulcers

    DEFF Research Database (Denmark)

    Holstein, P; Larsen, K; Sager, P

    1976-01-01

    Thirty-seven out of 38 neuropathic ulcers in 21 diabetic patients healed during relief of external pressure obtained by properly fitted interchangeable insoles. The time required for healing was 1 to 12 months (mean 3.6 months). The presence of mild occlussive arterial disease did not influence...

  3. Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation.

    Science.gov (United States)

    Huang, Yongzhi; Green, Alexander L; Hyam, Jonathan; Fitzgerald, James; Aziz, Tipu Z; Wang, Shouyan

    2018-01-01

    Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Use of Lidocaine Patches for Neuropathic Pain in a Comprehensive Cancer Centre

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    Julia Ann Fleming

    2009-01-01

    Full Text Available BACKGROUND: There are few reports of the use of the lidocaine 5% patch (L5%P for neuropathic pain (NP in the cancer patient. Within a comprehensive cancer centre, L5%P has been prescribed by the Pain and Palliative Care Service (Peter McCallum Cancer Centre, East Melbourne, Victoria, Australia for selected patients with NP since 2001.

  5. Prevalence of Neuropathic Pain in Radiotherapy Oncology Units

    International Nuclear Information System (INIS)

    Manas, Ana; Monroy, Jose Luis; Ramos, Avelino Alia; Cano, Carmen; Lopez-Gomez, Vanessa; Masramon, Xavier; Perez, Maria

    2011-01-01

    Purpose: Neuropathic pain (NP) in cancer patients severely impacts quality of life. Radiotherapy (RT) may cause NP, and at the same time, cancer patients visit RT units for pain relief. NP prevalence at these sites and current analgesic treatment should be assessed to improve management. Methods and Materials: This epidemiological, prospective, multicenter study was undertaken to assess NP prevalence, according to Douleur Neuropathique 4 questions questtionaire (DN4) test results, and analgesic management in cancer pain patients visiting RT oncologic units. Secondary analyses assessed NP etiology and pain intensity (using the Brief Pain Inventory-Short Form) and impact (using the Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study [MOS] for Sleep, and the Health Survey Short Form-12). Results: A total of 1,098 patients with any kind of pain were registered. NP prevalence was 31.1% (95% confidence interval, 28.4%--33.9%); 291 NP patients (mean age, 62.2 ±12.5 years and 57.7% men) were eligible for study; 49% of patients were overweight. The most frequent tumors were those of breast and lung, and stage IIIB was the most common cancer stage. The tumors caused 75% of NP cases. Anxiety, sleepiness, and depression were common. At 8 weeks, pain intensity and interference with daily activities decreased significantly for 50.8% of responders. Depression and anxiety (p < 0.0001) scores on the Physical Component Summary and Mental Component Summary measures (p < 0.0001) and all MOS-Sleep subscales, except for snoring, improved significantly. The percentage of satisfied patients increased from 13.8% to 87.4% (p < 0.0001) with the current analgesic treatment, which meant a 1.2- and 6-fold increase (p < 0.0001) in narcotic analgesics and anticonvulsants, respectively, compared to previous treatment. Conclusions: NP is highly prevalent at RT oncology units, with sleepiness, anxiety, and depression as frequent comorbidities. There is a need to improve management

  6. The Effect of Intrathecal Administration of Muscimol on Modulation of Neuropathic Pain Symptoms Resulting from Spinal Cord Injury; an Experimental Study

    Directory of Open Access Journals (Sweden)

    Marjan Hosseini

    2014-09-01

    Full Text Available Introduction: Neuropathic pain can be very difficult to treat and it is one of the important medical challenging about pain treatments. Muscimol as a new agonist of gamma-Aminobutyric acid receptor type A (GABAA have been introduced for pain management. Thus, the present study was performed to evaluate the pain alleviating effect of intrathecal injection of different doses of muscimol as GABAA receptor agonist in spinal cord injury (SCI model of neuropathic pain. Methods: In the present experimental study male Wistar rats were treated by muscimol 0.01, 0.1 or 1 µg/10ul, intrathecally (i.t. three weeks after induction of spinal cord injury using compression injury model. Neuropathic pain symptoms were assessed at before treatment, 15 minutes, one hour and three hours after muscimol administration. The time of peak effect and optimum dosage was assessed by repeated measures analysis of variance and analysis of covariance, respectively. Results: Muscimol with the dose of 0.01 µg in 15 minutes caused to improve the thermal hyperalgesia (df: 24, 5; F= 6.6; p<0.001, mechanical hyperalgesia (df: 24, 5; F= 7.8; p<0.001, cold allodynia (df: 24, 5; F= 6.96; p<0.001, and mechanical allodynia (df: 24, 5; F= 15.7; p<0.001. The effect of doses of 0.1 µg and 1 µg were also significant. In addition, the efficacy of different doses of muscimol didn't have difference on thermal hyperalgesia (df: 24, 5; F= 1.52; p= 0.24, mechanical hyperalgesia (df: 24, 5; F= 0.3; p= -0.75, cold allodynia (df: 24, 5; F= 0.8; p= -0.56, and mechanical allodynia (df: 24, 5; F= 1.75; p= 0.86. Conclusion: The finding of the present study revealed that using muscimol with doses of 0.01µg, 0.1µg, and 1 µg reduces the symptoms of neuropathic pain. Also the effect of GABAA agonist is short term and its effectiveness gradually decreases by time.

  7. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Attal, Nadine; de Andrade, Daniel C; Adam, Frédéric; Ranoux, Danièle; Teixeira, Manoel J; Galhardoni, Ricardo; Raicher, Irina; Üçeyler, Nurcan; Sommer, Claudia; Bouhassira, Didier

    2016-05-01

    Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain, but the quality of the evidence is low. We aimed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain. We did a randomised, double-blind, placebo-controlled trial at two outpatient clinics in France (Clinical Pain Centre, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, and Neurological Centre, Hôpital Dupuytren, Limoges) and one in Brazil (Neurological Department, Hospital das Clínicas da FMUSP, São Paulo). Patients aged 18-85 years with peripheral neuropathic pain were randomly assigned (1:1) by block randomisation, according to a centralised schedule, to receive two subcutaneous administrations of botulinum toxin A (up to 300 units) or placebo, 12 weeks apart. All patients and investigators were masked to treatment assignment. The primary outcome was the efficacy of botulinum toxin A versus placebo, measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration. The primary efficacy analysis was a mixed-model repeated-measures analysis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01251211. Between Oct 2, 2010, and Aug 2, 2013, 152 patients were enrolled, of whom 68 were randomly assigned (34 per group), and 66 (37 [56%] men) were included in the primary analysis (34 in the botulinum toxin A group and 32 in the placebo group). Botulinum toxin A reduced pain intensity over 24 weeks compared with placebo (adjusted effect estimate -0·77, 95% CI -0·95 to -0·59; pbotulinum toxin A group and 17 (53%) of those in the placebo group (p=1·0). Severe pain was experienced by ten (29%) participants in the botulinum toxin A group and 11 (34%) in the placebo group (p=0·8). Two administrations of botulinum toxin A, each of which comprised several injections, have a

  8. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies

    Directory of Open Access Journals (Sweden)

    Zlateva Gergana

    2010-11-01

    Full Text Available Abstract Background Older patients are typically underrepresented in clinical trials of medications for chronic pain. A post hoc analysis of multiple clinical studies of pregabalin in patients with painful diabetic peripheral neuropathy (DPN or postherpetic neuralgia (PHN was conducted to evaluate the efficacy and safety of pregabalin in older patients. Methods Data from 11 double-blind, randomized, placebo-controlled clinical studies of pregabalin in patients with DPN or PHN were pooled. Efficacy outcomes included change in Daily Pain Rating Scale score, ≥30% and ≥50% responders, and endpoint pain score ≤3. Safety was based on adverse events (AEs. Primary efficacy was analyzed by analysis of covariance with terms for treatment, age category, protocol, baseline pain, and treatment-by-age category interaction. Results 2516 patients (white, n = 2344 [93.2%]; men, n = 1347 [53.5%]; PHN, n = 1003 [39.9%]; pregabalin, n = 1595 were included in the analysis. Patients were grouped by age: 18 to 64 years (n = 1236, 65 to 74 years (n = 766, and ≥75 years (n = 514. Baseline mean pain and sleep interference scores were comparable across treatment and age groups. Significant improvements in endpoint mean pain were observed for all pregabalin dosages versus placebo in all age groups (p ≤ 0.0009, except for the lowest dosage (150 mg/day in the youngest age group. Clinically meaningful pain relief, defined as ≥30% and ≥50% pain response, was observed in all age groups. The most common AEs were dizziness, somnolence, peripheral edema, asthenia, dry mouth, weight gain, and infections. The relative risks for these AEs increased with pregabalin dose, but did not appear related to older age or type of neuropathic pain. Conclusions Pregabalin (150-600 mg/day significantly reduced pain in older patients (age ≥65 years with neuropathic pain and improvements in pain were comparable to those observed in younger patients. Titration of pregabalin to the

  9. The application of neuropathic pain questionnaires in burning mouth syndrome patients.

    Science.gov (United States)

    Heo, Jun-Young; Ok, Soo-Min; Ahn, Yong-Woo; Ko, Myung-Yun; Jeong, Sung-Hee

    2015-01-01

    To evaluate and compare the validity of the PainDETECT, DN4, and abbreviated DN4 (DN4i) neuropathic pain questionnaires for primary burning mouth syndrome (BMS), which is a burning sensation in the oral mucosa in the absence of any identifiable organic etiology. Eighty-one patients (42 with primary BMS and 39 with nociceptive pain) complaining of a burning sensation and pain in their oral mucosa were enrolled in this study. All of the patients completed the neuropathic pain questionnaires. The sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic (ROC) curve were estimated. Then the relationship between pain intensity and total neuropathic pain score was investigated. Data were analyzed with the chi-square test and independent t test for subjects' baseline characteristic differences, and with Pearson correlation coefficients for the relationship of variables. The mean area under the ROC curves (AUCs) for PainDETECT, DN4, and DN4i were 0.81, 0.79, and 0.81, respectively. There was no statistically significant difference in the AUCs among the questionnaires. PainDETECT, DN4, and DN4i had a lower sensitivity and specificity for BMS compared to previous validation studies. The total scores for PainDETECT, DN4, and DN4i in the primary BMS group were significantly associated with pain intensity. Although the results of this study suggest that neuropathic pain questionnaires, such as PainDETECT and DN4, are not ideal principal screening tools for BMS patients, a substantial proportion of neuropathic symptoms in primary BMS patients were identified.

  10. Blocking spinal CCR2 with AZ889 reversed hyperalgesia in a model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Vaillancourt François

    2010-12-01

    Full Text Available Abstract Background The CCR2/CCL2 system has been identified as a regulator in the pathogenesis of neuropathy-induced pain. However, CCR2 target validation in analgesia and the mechanism underlying antinociception produced by CCR2 antagonists remains poorly understood. In this study, in vitro and in vivo pharmacological approaches using a novel CCR2 antagonist, AZ889, strengthened the hypothesis of a CCR2 contribution to neuropathic pain and provided confidence over the possibilities to treat neuropathic pain with CCR2 antagonists. Results We provided evidence that dorsal root ganglia (DRG cells harvested from CCI animals responded to stimulation by CCL2 with a concentration-dependent calcium rise involving PLC-dependent internal stores. This response was associated with an increase in evoked neuronal action potentials suggesting these cells were sensitive to CCR2 signalling. Importantly, treatment with AZ889 abolished CCL2-evoked excitation confirming that this activity is CCR2-mediated. Neuronal and non-neuronal cells in the spinal cord were also excited by CCL2 applications indicating an important role of spinal CCR2 in neuropathic pain. We next showed that in vivo spinal intrathecal injection of AZ889 produced dose-dependent analgesia in CCI rats. Additionally, application of AZ889 to the exposed spinal cord inhibited evoked neuronal activity and confirmed that CCR2-mediated analgesia involved predominantly the spinal cord. Furthermore, AZ889 abolished NMDA-dependent wind-up of spinal withdrawal reflex pathway in neuropathic animals giving insight into the spinal mechanism underlying the analgesic properties of AZ889. Conclusions Overall, this study strengthens the important role of CCR2 in neuropathic pain and highlights feasibility that interfering on this mechanism at the spinal level with a selective antagonist can provide new analgesia opportunities.

  11. Neuropathic pain characteristics in patients from Curitiba (Brazil) with spinal cord injury.

    Science.gov (United States)

    Vall, Janaína; Costa, Carlos Mauricio de Castro; Santos, Terezinha de Jesus Teixeira; Costa, Samuel Bovy de Castro

    2011-02-01

    This was a descriptive cross-sectional study on patients with spinal cord injuries living in Curitiba, Paraná, Brazil. The aim was to evaluate the pain characteristics among such patients seen at referral care centers for spinal cord injury patients in Curitiba. A total of 109 adults with spinal cord injury in this city were evaluated regarding the presence of pain, especially neuropathic pain. Neuropathic pain was evaluated using the DN4 questionnaire, a universal instrument that has been translated and validated for Portuguese. A visual analog scale (VAS) was used to evaluate the intensity of pain. The prevalence of pain among these 109 patients was 31.2% (34 patients). The nociceptive pain presented was classified as musculoskeletal pain (nine patients), visceral pain (four patients) and mixed pain (one patient), thus totaling 14 patients (12.8%). Another 20 patients (18.3%) showed symptoms of neuropathic pain and fulfilled the criteria for neuropathic pain with scores greater than 4 out 10 in the DN4 questionnaire. Regarding the characteristics of the patients with neuropathic pain, most of them were male, younger than 40 years of age and paraplegic with incomplete lesions. They had become injured from 1 to more than 5 years earlier. The predominant etiology was gunshot wounds, and the intensity of their pain was high, with VAS scores greater than 5. This study partially corroborates other studies conducted on this subject. Studies of this type are important for understanding the profile of these patients, for the purpose of designing strategies for their rehabilitation, with a focus on the appropriate treatment and management of pain.

  12. Neuropathic pain characteristics in patients from Curitiba (Brazil with spinal cord injury

    Directory of Open Access Journals (Sweden)

    Janaína Vall

    2011-02-01

    Full Text Available This was a descriptive cross-sectional study on patients with spinal cord injuries living in Curitiba, Paraná, Brazil. The aim was to evaluate the pain characteristics among such patients seen at referral care centers for spinal cord injury patients in Curitiba. A total of 109 adults with spinal cord injury in this city were evaluated regarding the presence of pain, especially neuropathic pain. Neuropathic pain was evaluated using the DN4 questionnaire, a universal instrument that has been translated and validated for Portuguese. A visual analog scale (VAS was used to evaluate the intensity of pain. The prevalence of pain among these 109 patients was 31.2% (34 patients. The nociceptive pain presented was classified as musculoskeletal pain (nine patients, visceral pain (four patients and mixed pain (one patient, thus totaling 14 patients (12.8%. Another 20 patients (18.3% showed symptoms of neuropathic pain and fulfilled the criteria for neuropathic pain with scores greater than 4 out 10 in the DN4 questionnaire. Regarding the characteristics of the patients with neuropathic pain, most of them were male, younger than 40 years of age and paraplegic with incomplete lesions. They had become injured from 1 to more than 5 years earlier. The predominant etiology was gunshot wounds, and the intensity of their pain was high, with VAS scores greater than 5. This study partially corroborates other studies conducted on this subject. Studies of this type are important for understanding the profile of these patients, for the purpose of designing strategies for their rehabilitation, with a focus on the appropriate treatment and management of pain.

  13. Cortical and white matter alterations in patients with neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Yoon, Eun Jin; Kim, Yu Kyeong; Shin, Hyung Ik; Lee, Youngjo; Kim, Sang Eun

    2013-12-02

    Neuropathic pain is one of the major problems of patients with spinal cord injury (SCI), which remains refractory to treatment despite a variety of therapeutic approach. Multimodal neuroimaging could provide complementary information for brain mechanisms underlying neuropathic pain, which could be based on development of more effective treatment strategies. Ten patients suffering from chronic neuropathic pain after SCI and 10 healthy controls underwent FDG-PET, T1-anatomical MRI and diffusion tensor imaging. We found decreases of both metabolism and the gray matter volume in the left dorsolateral prefrontal cortex in patients compared to healthy controls, as well as hypometabolism in the medial prefrontal cortex and gray matter volume loss in bilateral anterior insulae and subgenual anterior cingulate cortices. These brain regions are generally known to participate in pain modulation by affective and cognitive processes. Decreases of mean diffusivity (MD) in the right internal capsule including, cerebral peduncle, pre-and post-central white matter, and prefrontal white matter as components of the corticospinal and thalamocortical tracts were demonstrated in patients. Further, lower MD value of prefrontal white matter was correlated with decreased metabolism of medial prefrontal cortex in patients. These results indicated that white matter changes imply abnormal pain modulation in patients as well as motor impairment. Our study showed the functional and structural multimodal imaging modality commonly identified the possible abnormalities in the brain regions participating pain modulation in neuropathic pain. Multifaceted imaging studies in neuropathic pain could be useful elucidating precise mechanisms of persistent pain, and providing future directions for treatment. © 2013 Elsevier B.V. All rights reserved.

  14. Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states

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    Martinez Jose A

    2012-01-01

    Full Text Available Abstract Background Although pregabalin therapy is beneficial for neuropathic pain (NeP by targeting the CaVα2δ-1 subunit, its site of action is uncertain. Direct targeting of the central nervous system may be beneficial for the avoidance of systemic side effects. Results We used intranasal, intrathecal, and near-nerve chamber forms of delivery of varying concentrations of pregabalin or saline delivered over 14 days in rat models of experimental diabetic peripheral neuropathy and spinal nerve ligation. As well, radiolabelled pregabalin was administered to determine localization with different deliveries. We evaluated tactile allodynia and thermal hyperalgesia at multiple time points, and then analyzed harvested nervous system tissues for molecular and immunohistochemical changes in CaVα2δ-1 protein expression. Both intrathecal and intranasal pregabalin administration at high concentrations relieved NeP behaviors, while near-nerve pregabalin delivery had no effect. NeP was associated with upregulation of CACNA2D1 mRNA and CaVα2δ-1 protein within peripheral nerve, dorsal root ganglia (DRG, and dorsal spinal cord, but not brain. Pregabalin's effect was limited to suppression of CaVα2δ-1 protein (but not CACNA2D1 mRNA expression at the spinal dorsal horn in neuropathic pain states. Dorsal root ligation prevented CaVα2δ-1 protein trafficking anterograde from the dorsal root ganglia to the dorsal horn after neuropathic pain initiation. Conclusions Either intranasal or intrathecal pregabalin relieves neuropathic pain behaviours, perhaps due to pregabalin's effect upon anterograde CaVα2δ-1 protein trafficking from the DRG to the dorsal horn. Intranasal delivery of agents such as pregabalin may be an attractive alternative to systemic therapy for management of neuropathic pain states.

  15. Low doses of dextromethorphan have a beneficial effect in the treatment of neuropathic pain.

    Science.gov (United States)

    Morel, Véronique; Pickering, Gisèle; Etienne, Monique; Dupuis, Amandine; Privat, Anne-Marie; Chalus, Maryse; Eschalier, Alain; Daulhac, Laurence

    2014-12-01

    N-methyl-D-aspartate receptor (NMDAR) antagonists may be given in persistent neuropathic pain, but adverse events especially with ketamine may limit their clinical use. Less central and cognitive adverse events are described with dextromethorphan and memantine. These molecules have been explored in many preclinical and clinical studies, but data are conflicting as regards neuropathic pain alleviation. Dextromethorphan and memantine have been administered to animals after spinal nerve ligation (SNL) to evaluate their antinociceptive/cognitive effects and associated molecular events, including the phosphorylation of several tyrosine (pTyr(1336), pTyr(1472)) residues in the NR2B NMDAR subunit. Spinal nerve ligation and sham animals received dextromethorphan (10 mg/kg, i.p.), memantine (20 mg/kg, i.p.) or saline (1 mL/kg, i.p.). These drugs were administered once symptoms of allodynia and hyperalgesia had developed. Tests were carried out before and after surgery. Tactile allodynia, mechanical hyperalgesia and spatial memory were, respectively, evaluated by von Frey, Randall & Selitto and Y-maze tests and molecular events by Western blot analysis. Spinal nerve-ligated animals displayed nociception and impaired spatial memory. Dextromethorphan, but not memantine, reversed neuropathic pain (NP) symptoms, restored spatial memory integrity and decreased the expression of pTyr(1336)NR2B. Following postoperative administration of dextromethorphan, this study has demonstrated for the first time a concordance between behaviour, cognitive function and molecular events via pTyr(1336)NR2B for neuropathic pain alleviation. Confirmation of these findings in patients would constitute a major step forward in the treatment of neuropathic pain and in the improvement of cognitive function and quality of life. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  16. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

  17. Biosensor Detection of Neuropathy Target Esterase in Whole Blood as a Biomarker of Exposure to Neuropathic Organophosphorus Compounds

    National Research Council Canada - National Science Library

    Makhaeva, Galina F; Sigolaeva, Larisa V; Zhuravleva, Lyudmila Z; Eremenko, Arkady V; Kurochkin, Ilya N; Malygin, Vladimir V; Richardson, Rudy J

    2002-01-01

    .... Lymphocyte NTE has also found use as a biomarker of human exposure to neuropathic OPs. Recently, a sensitive NTE biosensor was developed using a tyrosinase carbon-paste electrode for amperometric (Amp...

  18. Baicalin ameliorates neuropathic pain by suppressing HDAC1 expression in the spinal cord of spinal nerve ligation rats

    Directory of Open Access Journals (Sweden)

    Chen-Hwan Cherng

    2014-08-01

    Conclusion: The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats.

  19. Pain-related psychological distress, self-rated health and significance of neuropathic pain in Danish soldiers injured in Afghanistan

    DEFF Research Database (Denmark)

    Duffy, J R; Warburg, Finn; Koelle, S-F T

    2015-01-01

    BACKGROUND: Pain and mental health concerns are prevalent among veterans. While the majority of research has focused on chronic pain as an entity, there has been little work directed towards investigating the role of neuropathic pain in relation to psychological comorbidity. As such, we...... hypothesised that participants with signs of neuropathic pain would report higher levels of psychological distress and diminished self-rated health compared to those without a neuropathic component. METHODS: A retrospective review of standardised questionnaires (PainDETECT Questionnaire, Post-traumatic Stress...... pain. RESULTS: Fifty-three participants were included. The Post-traumatic Stress Disorder Checklist-Civilian score was in median (interquartile range) 26 (22-31), the Hospital Anxiety and Depression Scale score was 4 (2-6.5) and 2 (1-5) for anxiety and depression respectively. Evidence of neuropathic...

  20. Neurophysiological and histopathological evaluation of small fiber pathways as diagnostic characterization of neuropathic pain and autonom dysfunction syndromes

    OpenAIRE

    Devigli, Grazia

    2012-01-01

    This manuscript is made up of two individual not related articles about peripheral neuropathic pain syndrome. The first article reports the effect on pain relief in patients with peripheral neuropathic pain after brachial plexus lesions or distal peripheral nerve injury using an implanted peripheral nerve stimulator applied directly on nerve branch using a peculiar surgical technique. Seven patients with post-traumatic lesion of brachial plexus or peripheral nerve complaining severe intractab...

  1. Blocking mammalian target of rapamycin (mTOR improves neuropathic pain evoked by spinal cord injury

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    Wang Xiaoping

    2016-01-01

    Full Text Available Spinal cord injury (SCI is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1 and p70 ribosomal S6 protein kinase 1 (S6K1 in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

  2. Needs and requests--patients and physicians voices about improving the management of spinal cord injury neuropathic pain.

    Science.gov (United States)

    Norrbrink, Cecilia; Löfgren, Monika

    2016-01-01

    The present purpose was to explore patients' and involved physicians' needs and requests for improving their management of neuropathic pain following spinal cord injury (SCI). Sixteen patients with SCI and neuropathic pain, and nine physicians, were interviewed in focus-groups or individual interviews. An emergent design was used and the interviews and analyses were carried out in parallel, making it possible to use and deepen new emerging knowledge. The interviews were transcribed verbatim and processed according to content analysis. A final model with four themes described the results. Three themes covered the current situation: limitations in structure, lack of knowledge and competence, and frustrations. A fourth theme, needs and requests, described suggestions by patients and physicians for future improvements. Suggestions included increased participation, increased patient involvement in the pain rehabilitation process, support in the process of learning to live with pain, implementation of multi-modal pain rehabilitation, and the use of complementary treatments for neuropathic pain. Neuropathic pain following SCI needs to be assessed and treated using a structured, inter-disciplinary, multi-modal rehabilitation approach involving patients in planning and decision-making. For improving SCI neuropathic pain management, there is a great need for individually-tailored management, planned in a dialogue on equal terms between health care and the patient. Patients desire continuity and regularity and the possibility of receiving complementary treatments for SCI neuropathic pain. Access to structured pain rehabilitation is needed. Support and tools need to be provided in the learning-to-live with pain process.

  3. Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

    Science.gov (United States)

    Mehta, Ashish K; Bhati, Yogendra; Tripathi, Chakra D; Sharma, Krishna K

    2014-08-01

    Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2 weeks in doses of 50, 100 and 200 mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50 mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100 mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.

  4. Neuropathic ocular pain: an important yet underevaluated feature of dry eye

    Science.gov (United States)

    Galor, A; Levitt, R C; Felix, E R; Martin, E R; Sarantopoulos, C D

    2015-01-01

    Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain. PMID:25376119

  5. The role of the immune system in the generation of neuropathic pain.

    Science.gov (United States)

    Calvo, Margarita; Dawes, John M; Bennett, David L H

    2012-07-01

    Persistent pain is a sequela of several neurological conditions with a primary immune basis, such as Guillain-Barré syndrome and multiple sclerosis. Additionally, diverse forms of injury to the peripheral or the central nervous systems--whether traumatic, metabolic, or toxic--result in substantial recruitment and activation of immune cells. This response involves the innate immune system, but evidence also exists of T-lymphocyte recruitment, and in some patient cohorts antibodies to neuronal antigens have been reported. Mediators released by immune cells, such as cytokines, sensitise nociceptive signalling in the peripheral and central nervous systems. Preclinical data suggest an immune pathogenesis of neuropathic pain, but clinical evidence of a central role of the immune system is less clear. An important challenge for the future is to establish to what extent this immune response initiates or maintains neuropathic pain in patients and thus whether it is amenable to therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Neuroimmune-Driven Neuropathic Pain Establishment: A Focus on Gender Differences

    Directory of Open Access Journals (Sweden)

    Vincenzo Coraggio

    2018-01-01

    Full Text Available The role of neuroinflammatory cells in the establishment of neuropathic pain has been investigated in depth in the last few years. In particular, microglia have been shown to be key players in the induction of tactile allodynia, as they release proinflammatory molecules that, in turn, sensitize nociceptive neurons within the spinal cord. However, the role of peripheral immune cells such as macrophages, infiltrating monocytes, mast cells, and T-cells has been highlighted in the last few studies, even though the data are still conflicting and need to be clarified. Intriguingly, the central (microglia and peripheral (T-cell-adaptive immune cells that orchestrate maladaptive process-driven neuropathic pain seem to be involved in a gender-dependent manner. In this review, we highlight the role of the microglia and peripheral immune cells in chronic degenerative disease associated with neuro-immune-inflammatory processes.

  7. Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

    Science.gov (United States)

    Wen, Hui-Zhong; Gao, Shi-Hao; Zhao, Yan-Dong; He, Wen-Juan; Tian, Xue-Long; Ruan, Huai-Zhen

    2017-01-01

    Background: Transcranial direct current stimulation (tDCS) is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters. Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1) on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia. Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI), we measured pain thresholds before and after anodal-tDCS (A-tDCS) using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models). Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS) and contralateral-tDCS (con-tDCS) produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats. Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical applications. PMID

  8. Neuropathic pain prevalence following spinal cord injury: A systematic review and meta-analysis.

    Science.gov (United States)

    Burke, D; Fullen, B M; Stokes, D; Lennon, O

    2017-01-01

    Following spinal cord injury (SCI), chronic pain is a common secondary complication with neuropathic pain (NP) cited as one of the most distressing and debilitating conditions leading to poor quality of life, depression and sleep disturbances. Neuropathic pain presenting at or below the level of injury is largely refractory to current pharmacological and physical treatments. No consensus on the prevalence of NP post SCI currently exists, hence this systematic review was undertaken. The review comprised three phases: a methodological assessment of databases [PubMed, Embase, Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library and Physiotherapy Evidence Database (PEDro)] identifying potential papers and screening for inclusion criteria by two independent reviewers; data extraction; and finally rating of internal validity and strength of the evidence, using a published valid and reliable scale. Meta-analysis estimated pooled point prevalence rates using a random effects model. In total, 17 studies involving 2529 patients were included in the review. Overall point prevalence rates for NP were established at 53% (38.58-67.47); 19% (13.26-26.39) for at-level NP and 27% (19.89-34.61) for below-level NP, with high heterogeneity noted (I 2  = 84-93%). Prevalence rates for NP following SCI are high. Future studies should include established definitions, classification systems and assessment tools for NP at defined time points post SCI to follow the trajectory of this problem across the lifespan and include indices of sleep, mood and interference to allow for appropriate, optimal and timely NP management for each patient. WHAT DOES THIS REVIEW ADD?: This is the first systematic review and meta-analysis to record pooled point prevalence of neuropathic pain post spinal cord injury at 53%. Additional pooled analysis shows that neuropathic pain is more common below the level of lesion, in patients with tetraplegia, older patients

  9. Thalamic deep brain stimulation for neuropathic pain after amputation or brachial plexus avulsion.

    Science.gov (United States)

    Pereira, Erlick A C; Boccard, Sandra G; Linhares, Paulo; Chamadoira, Clara; Rosas, Maria José; Abreu, Pedro; Rebelo, Virgínia; Vaz, Rui; Aziz, Tipu Z

    2013-09-01

    Fifteen hundred patients have received deep brain stimulation (DBS) to treat neuropathic pain refractory to pharmacotherapy over the last half-century, but few during the last decade. Deep brain stimulation for neuropathic pain has shown variable outcomes and gained consensus approval in Europe but not the US. This study prospectively evaluated the efficacy at 1 year of DBS for phantom limb pain after amputation, and deafferentation pain after brachial plexus avulsion (BPA), in a single-center case series. Patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, 36-Item Short-Form Health Survey (SF-36), Brief Pain Inventory (BPI), and University of Washington Neuropathic Pain Score (UWNPS). Twelve patients were treated over 29 months, receiving contralateral, ventroposterolateral sensory thalamic DBS. Five patients were amputees and 7 had BPAs, all from traumas. A postoperative trial of externalized DBS failed in 1 patient with BPA. Eleven patients proceeded to implantation and gained improvement in pain scores at 12 months. No surgical complications or stimulation side effects were noted. In the amputation group, after 12 months the mean VAS score improved by 90.0% ± 10.0% (p = 0.001), SF-36 by 57.5% ± 97.9% (p = 0.127), UWNPS by 80.4% ± 12.7% (p stimulation demonstrated efficacy at 1 year for chronic neuropathic pain after traumatic amputation and BPA. Clinical trials that retain patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.

  10. Advancing Nursing Practice: Management of Neuropathic Pain With Capsaicin 8% Without Physician Supervision.

    Science.gov (United States)

    O'Brien, Joanne; Keaveny, Joseph; Pollard, Valerie; Nugent, Linda Elizabeth

    The purpose of this study was to examine the management of patient's neuropathic pain with capsaicin 8% in a nurse-led clinic when administered by 1 registered advanced nurse practitioner without physician supervision. A longitudinal, single-group, descriptive research design was used to assess pain scores and quality of life 3 times over 3 months after treatment. Patients with a diagnosis of neuropathic pain were assessed and treated with capsaicin 8% by 1 advanced nurse practitioner with prescriptive authority in a nurse-led clinic. Pain scores were collected at baseline, and self-assessed pain, activity level, and quality of life were assessed at 1 week, 4 weeks, and 3 months after treatment. Twenty-four patients were recruited, and data were analyzed using Friedman's test. In post hoc analysis, Wilcoxon signed-rank test was used with Bonferroni correction. Pain scores differed from pretreatment to posttreatment at each of the 3 time points, at rest (χ3 = 20.54, P = .001) and on movement (χ3 = 23.644, P = .001), and remained significant after Bonferroni correction. Overall, 62.5% (n = 15) of patients achieved at least a 30% reduction in self-reported pain at rest from pretreatment to 3 months, and 54% (n = 13) achieved the same reduction in pain on movement. Most improvements in patient's quality of life occurred between 1 and 4 weeks. Patient satisfaction was high, with 83% stating that they would be happy to have the treatment repeated. Single-dose capsaicin 8% decreased neuropathic pain after being administered in an outpatient setting by an experienced registered advanced nurse practitioner. Further multicenter research led by advanced nurse practitioners is needed to support high-quality, safe treatment of neuropathic pain with high-concentration capsaicin in nurse-led chronic pain clinics.

  11. A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury

    Directory of Open Access Journals (Sweden)

    Wu Ann

    2011-01-01

    Full Text Available Abstract Background A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. Results We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs or in astrocyte and microglia activation in the spinal dorsal and ventral horns. Conclusions These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.

  12. Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice.

    Science.gov (United States)

    Yang, Pao-Pao; Yeh, Geng-Chang; Huang, Eagle Yi-Kung; Law, Ping-Yee; Loh, Horace H; Tao, Pao-Luh

    2015-09-22

    Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model. Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α). Co-administration of DM10 potentiated these effects of oxycodone. The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.

  13. Neuropathic pain and use of PainDETECT in patients with fibromyalgia: a cohort study

    OpenAIRE

    Gauffin, Jarno; Hankama, Tiina; Kautiainen, Hannu; Hannonen, Pekka; Haanp??, Maija

    2013-01-01

    Abstract Backround Fibromyalgia has a plethorae of symptoms, which can be confusing and even misleading. Accurate evaluation is necessary when patients with fibromyalgia are treated. Different types of instruments are available for the clinicians to supplement evaluation. Our objective was to study the applicability of the PainDETECT instrument to screen neuropathic pain in patients with fibromyalgia. Methods 158 patients with primary fibromyalgia underwent a neurological examination includin...

  14. Neuropathic pain and use of PainDETECT in patients with fibromyalgia: a cohort study.

    Science.gov (United States)

    Gauffin, Jarno; Hankama, Tiina; Kautiainen, Hannu; Hannonen, Pekka; Haanpää, Maija

    2013-02-14

    Fibromyalgia has a plethorae of symptoms, which can be confusing and even misleading. Accurate evaluation is necessary when patients with fibromyalgia are treated. Different types of instruments are available for the clinicians to supplement evaluation. Our objective was to study the applicability of the PainDETECT instrument to screen neuropathic pain in patients with fibromyalgia. 158 patients with primary fibromyalgia underwent a neurological examination including bedside sensory testing. They also fulfilled four questionnaires: PainDETECT, Beck depression inventory IA (BDI IA), Fibromyalgia Impact Questionnaire (FIQ) and a self-made questionnaire regarding present pain and pain relieving methods of the patients. The results of the clinical evaluation and questionnaires were then compared. Clinically verified neuropathic pain was diagnosed in 53/158 [34% (95% Cl: 26 to 41)] patients. The ROC curve achieved a maximum Youden´s index at score of 17 when sensitivity was 0.79 (95% Cl: 0.66 to 0.89) and specificity 0.53 (95% Cl: 0.43 to 0.63). The PainDETECT total score (OR: 1.14 95% Cl: 1.06 to 1.22), FM as the worst current pain (OR: 0.31; 95% 0.16 to 0.62), body mass index (BMI) (OR: 1.05; 95% Cl: 1.00 to 1.11) and the intensity of current pain (OR: 1.20; 95% Cl: 1.01 to 1.41) were significantly associated with the presence of neuropathic pain in univariate analyses. This study highlights the importance of thorough clinical examination. The Neuropathic pain screening tool PainDETECT is not as useful in patients with fibromyalgia as in patients with uncompromised central pain control.

  15. Neuropathic pain and use of PainDETECT in patients with fibromyalgia: a cohort study

    Directory of Open Access Journals (Sweden)

    Gauffin Jarno

    2013-02-01

    Full Text Available Abstract Backround Fibromyalgia has a plethorae of symptoms, which can be confusing and even misleading. Accurate evaluation is necessary when patients with fibromyalgia are treated. Different types of instruments are available for the clinicians to supplement evaluation. Our objective was to study the applicability of the PainDETECT instrument to screen neuropathic pain in patients with fibromyalgia. Methods 158 patients with primary fibromyalgia underwent a neurological examination including bedside sensory testing. They also fulfilled four questionnaires: PainDETECT, Beck depression inventory IA (BDI IA, Fibromyalgia Impact Questionnaire (FIQ and a self-made questionnaire regarding present pain and pain relieving methods of the patients. The results of the clinical evaluation and questionnaires were then compared. Results Clinically verified neuropathic pain was diagnosed in 53/158 [34% (95% Cl: 26 to 41] patients. The ROC curve achieved a maximum Youden´s index at score of 17 when sensitivity was 0.79 (95% Cl: 0.66 to 0.89 and specificity 0.53 (95% Cl: 0.43 to 0.63. The PainDETECT total score (OR: 1.14 95% Cl: 1.06 to 1.22, FM as the worst current pain (OR: 0.31; 95% 0.16 to 0.62, body mass index (BMI (OR: 1.05; 95% Cl: 1.00 to 1.11 and the intensity of current pain (OR: 1.20; 95% Cl: 1.01 to 1.41 were significantly associated with the presence of neuropathic pain in univariate analyses. Conclusion This study highlights the importance of thorough clinical examination. The Neuropathic pain screening tool PainDETECT is not as useful in patients with fibromyalgia as in patients with uncompromised central pain control.

  16. Psychological defensive profile of sciatica patients with neuropathic pain and its relationship to quality of life.

    Science.gov (United States)

    Tutoglu, A; Boyaci, A; Karababa, I F; Koca, I; Kaya, E; Kucuk, A; Yetisgin, A

    2015-09-01

    To identify differences between defense styles and mechanisms in sciatica patients with or without neuropathic pain and their relationship to quality of life. The study included 37 sciatica patients with neuropathic pain (SNP), 36 sciatica patients without neuropathic pain and 38 healthy subjects. Pain severity was measured using the Visual Analogue Scale (VAS). Psychological condition was assessed using the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Defense mechanisms were assessed using a 40-item Defense Style Questionnaire (DSQ-40) and quality of life was assessed using Short Form-36 (SF-36). BDI and BAI scores were significantly higher in the SNP group (p < 0.001). Idealization and immature defense styles, as well as isolation, displacement and somatization were significantly higher in the SNP group (p < 0.05). SF-36 parameters also differed significantly between the groups, with controls having the best scores and the SNP group the worst. In linear regression analysis, acting out and BDI were found to affect the pain domain of the SF-36 (p < 0.001). The acting out defensive style and BDI were independently associated with pain-related quality of life. In the SNP group, significant differences were found in the immature and neurotic styles of the defense mechanisms.

  17. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

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    GURPREET KAUR

    2015-03-01

    Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

  18. Pain relief with lidocaine 5% patch in localized peripheral neuropathic pain in relation to pain phenotype

    DEFF Research Database (Denmark)

    Torgaard Demant, Dyveke; Lund, Karen; Finnerup, Nanna B

    2015-01-01

    In neuropathic pain with irritable nociceptor phenotype, up-regulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype-panel, cross-over study with 4-week treatment pe...... had an effect on peripheral neuropathic pain, and it may be most efficacious in patients with irritable nociceptor phenotype. The lack of significant phenotype differences may be caused by too low statistical power.......In neuropathic pain with irritable nociceptor phenotype, up-regulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype-panel, cross-over study with 4-week treatment...... periods of lidocaine 5% patch and placebo was performed to search for phenotype differences in effect. The primary efficacy measure was the total pain intensity on an 11-point numeric rating scale (NRS), and the primary objective was to compare the effect of lidocaine in patients with and without...

  19. Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease

    Science.gov (United States)

    Madorsky, Irina; Opalach, Katherine; Waber, Amanda; Verrier, Jonathan D.; Solmo, Chelsea; Foster, Thomas; Dunn, William A; Notterpek, Lucia

    2009-01-01

    Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of the peripheral nervous system. In this study we asked whether dietary restriction by intermittent fasting (IF) could alleviate the neuropathic phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that neuropathic mice kept on a five month long IF regimen had improved locomotor performance compared to ad libitum (AL) fed littermates. The functional benefits of this dietary intervention are associated with an increased expression of myelin proteins combined with a thicker myelin sheath, less redundant basal lamina, and a reduction in aberrant Schwann cell proliferation. These morphological improvements are accompanied by a decrease in PMP22 protein aggregates, and enhanced expression of cytosolic chaperones and constituents of the autophagy-lysosomal pathway. These results indicate that dietary restriction is beneficial for peripheral nerve function in TrJ neuropathic mice, as it promotes the maintenance of locomotor performance. PMID:19320048

  20. Experiences with spinal cord stimulator in patients with chronic neuropathic back pain.

    Science.gov (United States)

    Gjesdal, Kine; Furnes, Bodil; Dysvik, Elin

    2014-09-01

    Neuropathic pain is a complex, chronic, and disabling condition that has physical, functional, and psychosocial repercussions. Although the estimated prevalence of neuropathic pain in the general population ranges from 1.5% to 8%, neuropathic pain is frequently underdiagnosed and undertreated. The aims of this study were to examine the experience of patients treated with spinal cord stimulation as a pain-relieving treatment and how this may influence the patient's ability to participate in everyday life activities. A qualitative approach based on seven telephone interviews was performed. The participants were recruited from a university hospital in Norway, and all used spinal cord stimulation as a pain-relieving treatment. Qualitative content analysis was used. Two thematic findings emerged: (1) pain relief with spinal cord stimulation as a complex and individual experience and (2) challenges in adaptations in everyday life with spinal cord stimulation. Findings indicate that spinal cord stimulation can offer pain relief that can help patients achieve a meaningful life despite chronic pain. Spinal cord stimulation also may have disadvantages that should be considered before offering this treatment. It seems evident that extended information needs about working mechanism of SCS and precautions as well as follow-up are required to meet unexpected challenges in adaptation. Here the nurse has an important role when informing and following this patient group. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  1. Brain activity modifications following spinal cord stimulation for chronic neuropathic pain: A systematic review.

    Science.gov (United States)

    Bentley, L D; Duarte, R V; Furlong, P L; Ashford, R L; Raphael, J H

    2016-04-01

    Spinal cord stimulation (SCS) is believed to exert supraspinal effects; however, these mechanisms are still far from fully elucidated. This systematic review aims to assess existing neurophysiological and functional neuroimaging literature to reveal current knowledge regarding the effects of SCS for chronic neuropathic pain on brain activity, to identify gaps in knowledge, and to suggest directions for future research. Electronic databases and hand-search of reference lists were employed to identify publications investigating brain activity associated with SCS in patients with chronic neuropathic pain, using neurophysiological and functional neuroimaging techniques (fMRI, PET, MEG, EEG). Studies investigating patients with SCS for chronic neuropathic pain and studying brain activity related to SCS were included. Demographic data (age, gender), study factors (imaging modality, patient diagnoses, pain area, duration of SCS at recording, stimulus used) and brain areas activated were extracted from the included studies. Twenty-four studies were included. Thirteen studies used neuroelectrical imaging techniques, eight studies used haemodynamic imaging techniques, two studies employed both neuroelectrical and haemodynamic techniques separately, and one study investigated cerebral neurobiology. The limited available evidence regarding supraspinal mechanisms of SCS does not allow us to develop any conclusive theories. However, the studies included appear to show an inhibitory effect of SCS on somatosensory evoked potentials, as well as identifying the thalamus and anterior cingulate cortex as potential mediators of the pain experience. The lack of substantial evidence in this area highlights the need for large-scale controlled studies of this kind. © 2015 European Pain Federation - EFIC®

  2. Prevalence of acute neuropathic pain after cancer surgery: A prospective study

    Directory of Open Access Journals (Sweden)

    P N Jain

    2014-01-01

    Full Text Available Background and Aims: Acute neuropathic pain (ANP is an under-recognised and under-diagnosed condition and often difficult to treat. If left untreated, it may further transform into persistent post-operative chronic pain leading to a disability. Aims: This prospective study was undertaken on 300 patients to identify the prevalence of ANP in the post-operative period by using a neuropathic pain detection questionnaire tool. Methods: This is an open-label study in which patients with six different types of cancer surgeries (Thoracic, gastro-intestinal, gynae/urology, bone/soft-tissue, head and neck and breast subgroups-50 each were included for painDETECT questionnaire tool on the 2 nd and 7 th day surgery. Results: This study found a 10% point prevalence of ANP. Analysis showed that 25 patients had ′possible′ ANP, the maximum from urological cancer surgery (6 followed by thoracic surgery (5. Five patients were found to have ′positive′ ANP including 2 groin node dissection, 2 hemipelvectomy and 1 oesophagectomy. Conclusion: Significant relationship between severity of post-operative pain was found with the occurrence of ANP in the post-operative period requiring a special attention to neuropathic pain assessment. Larger studies are required with longer follow-up to identify accurately the true prevalence and causative factors of ANP after surgery.

  3. Neuropathic pain mechanisms in patients with chronic sports injuries: a diagnostic model useful in sports medicine?

    Science.gov (United States)

    van Wilgen, Cornelis P; Keizer, Doeke

    2011-01-01

    The pathophysiology of chronic sports injuries such as overuse or tendinopathy remains largely unknown. With this exploratory study, we aim to detect signs of sensitization of the nervous system. Sensitization is an indication of the involvement of neuropathic mechanisms in patients with chronic sports injuries. Sensory descriptors were assessed by means of a neuropathic pain questionnaire (DN4-interview) and by three methods of sensory testing. The test results were integrated in a scoring system. Patients were recruited from an outpatient clinic of a University Medical Centre and at primary care physical therapy practices. Fifteen athletes with a unilateral chronic sports injury were included. All subjects filled out the seven-items of the DN4-interview to assess sensory descriptors. Next, the presence of brush-evoked allodynia was assessed and pain thresholds with Von Frey monofilaments and a pressure algometer were measured in all patients to determine signs of sensitization. Based on the scoring system, in 4 out of 15 patients (27%) the presence of sensitization could be detected. In two other patients, signs of hypoalgesia were observed. The involvement of sensitization as an explanation for the pain in chronic sports injuries is credible in a considerable proportion of patients. With respect to treatment, the establishment of such neuropathic pain mechanisms is of clinical significance. Wiley Periodicals, Inc.

  4. Proinsulin-expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions.

    Science.gov (United States)

    Sambataro, Maria; Sambado, Luisa; Trevisiol, Enrica; Cacciatore, Matilde; Furlan, Anna; Stefani, Piero Maria; Seganfreddo, Elena; Durante, Elisabetta; Conte, Stefania; Della Bella, Silvia; Paccagnella, Agostino; Dei Tos, Angelo Paolo

    2018-02-12

    Diabetic neuropathy is the most common complication of diabetes and is frequently associated with foot ischemia and infection, but its pathogenesis is controversial. We hypothesized that proinsulin expression in peripheral blood mononuclear cells is a process relevant to this condition and could represent a link among hyperglycemia, nerve susceptibility, and diabetic foot lesions. We assessed proinsulin expression by using flow cytometry in dendritic cells from control participants and patients with type 2 diabetic with or without peripheral neuropathy or accompanied by diabetic foot. Among 32 non-neuropathic and 120 neuropathic patients with type 2 diabetic, we performed leg electromyography and found average sensory sural nerve conduction velocities of 48 ± 4 and 30 ± 4 m/s, respectively ( P foot lesions, and 39 had neuroischemic foot lesions (allux oximetry diabetic population, but not in nondiabetic participants, a progressively increasing level of peripheral blood dendritic cell proinsulin expression was detected, which directly correlated with circulating TNF-α levels ( P diabetes, proinsulin-expressing blood cells, possibly via their involvement in innate immunity, may play a role in diabetic peripheral neuropathy and foot lesions.-Sambataro, M., Sambado, L., Trevisiol, E., Cacciatore, M., Furlan, A., Stefani, P. M., Seganfreddo, E., Durante, E., Conte, S., Della Bella, S., Paccagnella, A., dei Tos, A. P. Proinsulin-expressing dendritic cells in type 2 neuropathic diabetic patients with and without foot lesions.

  5. Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

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    Mark S. Cooper

    2011-01-01

    Full Text Available Electrophysiological conversion of chloride-dependent synapses from inhibitory to excitatory function, as a result of aberrant neuronal chloride homeostasis, is a known mechanism for the genesis of neuropathic pain. This paper examines theoretically how this type of synaptic conversion can disrupt circuit logic in spinal nociceptive circuits. First, a mathematical scaling factor is developed to represent local aberration in chloride electrochemical driving potential. Using this mathematical scaling factor, electrophysiological symbols are developed to represent the magnitude of synaptic conversion within nociceptive circuits. When inserted into a nociceptive circuit diagram, these symbols assist in understanding the generation of neuropathic pain associated with the collapse of transmembrane chloride gradients. A more generalized scaling factor is also derived to represent the interplay of chloride and bicarbonate driving potentials on the function of GABAergic and glycinergic synapses. These mathematical and symbolic representations of synaptic conversion help illustrate the critical role that anion driving potentials play in the transduction of pain. Using these representations, we discuss ramifications of glial-mediated synaptic conversion in the genesis, and treatment, of neuropathic pain.

  6. Aberrant TRPV1 expression in heat hyperalgesia associated with trigeminal neuropathic pain.

    Science.gov (United States)

    Urano, Hiroko; Ara, Toshiaki; Fujinami, Yoshiaki; Hiraoka, B Yukihiro

    2012-01-01

    Trigeminal neuropathic pain is a facial pain syndrome associated with trigeminal nerve injury. However, the mechanism of trigeminal neuropathic pain is poorly understood. This study aimed to determine the role of transient receptor potential vanilloid 1 (TRPV1) in heat hyperalgesia in a trigeminal neuropathic pain model. We evaluated nociceptive responses to mechanical and heat stimuli using a partial infraorbital nerve ligation (pIONL) model. Withdrawal responses to mechanical and heat stimuli to vibrissal pads (VP) were assessed using von Frey filaments and a thermal stimulator equipped with a heat probe, respectively. Changes in withdrawal responses were measured after subcutaneous injection of the TRP channel antagonist capsazepine. In addition, the expression of TRPV1 in the trigeminal ganglia was examined. Mechanical allodynia and heat hyperalgesia were observed in VP by pIONL. Capsazepine suppressed heat hyperalgesia but not mechanical allodynia. The number of TRPV1-positive neurons in the trigeminal ganglia was significantly increased in the large-diameter-cell group. These results suggest that TRPV1 plays an important role in the heat hyperalgesia observed in the pIONL model.

  7. Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

    Directory of Open Access Journals (Sweden)

    Ma Fei

    2012-12-01

    Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

  8. Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Madorsky, Irina; Opalach, Katherine; Waber, Amanda; Verrier, Jonathan D; Solmo, Chelsea; Foster, Thomas; Dunn, William A; Notterpek, Lucia

    2009-04-01

    Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of the peripheral nervous system. In this study we asked whether dietary restriction by intermittent fasting (IF) could alleviate the neuropathic phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that neuropathic mice kept on a five month long IF regimen had improved locomotor performance compared to ad libitum (AL) fed littermates. The functional benefits of this dietary intervention are associated with an increased expression of myelin proteins combined with a thicker myelin sheath, less redundant basal lamina, and a reduction in aberrant Schwann cell proliferation. These morphological improvements are accompanied by a decrease in PMP22 protein aggregates, and enhanced expression of cytosolic chaperones and constituents of the autophagy-lysosomal pathway. These results indicate that dietary restriction is beneficial for peripheral nerve function in TrJ neuropathic mice, as it promotes the maintenance of locomotor performance.

  9. Eligibility audits for the randomized neuropathic bone pain trial (TROG 96.05)

    International Nuclear Information System (INIS)

    Roos, D.E.; Turner, S.L.

    2000-01-01

    In February 1996 the Trans-Tasman Radiation Oncology Group (TROG) initiated a two-arm, multicentre, prospective randomized trial on radiotherapy for neuropathic pain due to bone metastases (TROG 96.05). This trial compares the response to a single 8-Gy fraction with 20 Gy in five fractions. The accrual target is 270 patients. In order to evaluate compliance with eligibility criteria after approximately 1 year of accrual, an independent audit of the first 42 randomized patients was commissioned. This found that only one of these patients did not have genuine neuropathic pain, but that this patient and seven others (19%) had infringements of other eligibility/exclusion criteria for the trial. Accordingly it was decided to continue the full audit up to 90 patients. This detected no further patients without genuine neuropathic pain, and found only one other eligibility infringement (1/48; 2%). It is concluded that this quality assurance (QA) measure undertaken early in the trial led to significantly improved clinician awareness of, and compliance with, eligibility/exclusion criteria. It also enabled an accurate comparison of outcome data for all randomized versus all eligible patients at the time of the preplanned first interim analysis at 90 patients. In view of the excellent compliance demonstrated in the second audit, a one-in-five sampling is proposed for future audits from centres that have already accrued at least five consecutive eligible patients. This is consistent with TROG QA guidelines now operational. Copyright (2000) Blackwell Science Pty Ltd

  10. Effective relief of neuropathic pain by adeno-associated virus-mediated expression of a small hairpin RNA against GTP cyclohydrolase 1

    Directory of Open Access Journals (Sweden)

    Chang Jin

    2009-11-01

    Full Text Available Abstract Background Recent studies show that transcriptional activation of GTP cyclohydrolase I (GCH1 in dorsal root ganglia (DRG is significantly involved in the development and persistency of pain symptoms. We thus hypothesize that neuropathic pain may be attenuated by down-regulation of GCH1 expression, and propose a gene silencing system for this purpose. Results To interrupt GCH1 synthesis, we designed a bidirectional recombinant adeno-associated virus encoding both a small hairpin RNA against GCH1 and a GFP reporter gene (rAAV-shGCH1. After rAAV-shGCH1 was introduced into the sciatic nerve prior to or following pain-inducing surgery, therapeutic efficacy and the underlying mechanisms were subsequently validated in animal models. The GFP expression data indicates that rAAV effectively delivered transgenes to DRG. Subsequently reduced GCH1 expression was evident from immunohistochemistry and western-blotting analysis. Along with the down-regulation of GCH1, the von Frey test correspondingly indicated a sharp decline in pain symptoms upon both pre- and post-treatment with rAAV-shGCH1. Interestingly, GCH1 down-regulation additionally led to decreased microglial activation in the dorsal horn, implying an association between pain attenuation and reduced inflammation. Conclusion Therefore, the data suggests that GCH1 levels can be reduced by introducing rAAV-shGCH1, leading to pain relief. Based on the results, we propose that GCH1 modulation may be developed as a clinically applicable gene therapy strategy to treat neuropathic pain.

  11. Abnormal polyamine metabolism is unique to the neuropathic forms of MPS: potential for biomarker development and insight into pathogenesis.

    Science.gov (United States)

    Hinderer, Christian; Katz, Nathan; Louboutin, Jean-Pierre; Bell, Peter; Tolar, Jakub; Orchard, Paul J; Lund, Troy C; Nayal, Mohamad; Weng, Liwei; Mesaros, Clementina; de Souza, Carolina F M; Dalla Corte, Amauri; Giugliani, Roberto; Wilson, James M

    2017-10-01

    The mucopolysaccharidoses (MPS) are rare genetic disorders marked by severe somatic and neurological symptoms. Development of treatments for the neurological manifestations of MPS has been hindered by the lack of objective measures of central nervous system disease burden. Identification of biomarkers for central nervous system disease in MPS patients would facilitate the evaluation of new agents in clinical trials. High throughput metabolite screening of cerebrospinal fluid (CSF) samples from a canine model of MPS I revealed a marked elevation of the polyamine, spermine, in affected animals, and gene therapy studies demonstrated that reduction of CSF spermine reflects correction of brain lesions in these animals. In humans, CSF spermine was elevated in neuropathic subtypes of MPS (MPS I, II, IIIA, IIIB), but not in subtypes in which cognitive function is preserved (MPS IVA, VI). In MPS I patients, elevated CSF spermine was restricted to patients with genotypes associated with CNS disease and was reduced following hematopoietic stem cell transplantation, which is the only therapy currently capable of improving cognitive outcomes. Additional studies in cultured neurons from MPS I mice showed that elevated spermine was essential for the abnormal neurite overgrowth exhibited by MPS neurons. These findings offer new insights into the pathogenesis of CNS disease in MPS patients, and support the use of spermine as a new biomarker to facilitate the development of next generation therapeutics for MPS. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Long-Chain Omega-3 Fatty Acids Supplementation Accelerates Nerve Regeneration and Prevents Neuropathic Pain Behavior in Mice

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    Rafaela V. Silva

    2017-10-01

    Full Text Available Fish oil (FO is the main source of long chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs, which display relevant analgesic and anti-inflammatory properties. Peripheral nerve injury is driven by degeneration, neuroinflammation, and neuronal plasticity which results in neuropathic pain (NP symptoms such as allodynia and hyperalgesia. We tested the preventive effect of an EPA/DHA-concentrate fish oil (CFO on NP development and regenerative features. Swiss mice received daily oral treatment with CFO 4.6 or 2.3 g/kg for 10 days after NP was induced by partial sciatic nerve ligation. Mechanical allodynia and thermal hypernociception were assessed 5 days after injury. CFO 2.3 g/kg significantly prevented mechanical and thermal sensitization, reduced TNF levels in the spinal cord, sciatic MPO activity, and ATF-3 expression on DRG cells. CFO improved Sciatic Functional Index (SFI as well as electrophysiological recordings, corroborating the increased GAP43 expression and total number of myelinated fibers observed in sciatic nerve. No locomotor activity impairment was observed in CFO treated groups. These results point to the regenerative and possibly protective properties of a combined EPA and DHA oral administration after peripheral nerve injury, as well as its anti-neuroinflammatory activity, evidencing ω-3 PUFAs promising therapeutic outcomes for NP treatment.

  13. D-Aspartate Modulates Nociceptive-Specific Neuron Activity and Pain Threshold in Inflammatory and Neuropathic Pain Condition in Mice

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    Serena Boccella

    2015-01-01

    Full Text Available D-Aspartate (D-Asp is a free D-amino acid found in the mammalian brain with a temporal-dependent concentration based on the postnatal expression of its metabolizing enzyme D-aspartate oxidase (DDO. D-Asp acts as an agonist on NMDA receptors (NMDARs. Accordingly, high levels of D-Asp in knockout mice for Ddo gene (Ddo−/− or in mice treated with D-Asp increase NMDAR-dependent processes. We have here evaluated in Ddo−/− mice the effect of high levels of free D-Asp on the long-term plastic changes along the nociceptive pathway occurring in chronic and acute pain condition. We found that Ddo−/− mice show an increased evoked activity of the nociceptive specific (NS neurons of the dorsal horn of the spinal cord (L4–L6 and a significant decrease of mechanical and thermal thresholds, as compared to control mice. Moreover, Ddo gene deletion exacerbated the nocifensive responses in the formalin test and slightly reduced pain thresholds in neuropathic mice up to 7 days after chronic constriction injury. These findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.

  14. Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat

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    Ikeda Hiroshi

    2012-06-01

    Full Text Available Abstract Background The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain. Results In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP. Conclusions These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

  15. Identification of key genes and pathways associated with neuropathic pain in uninjured dorsal root ganglion by using bioinformatic analysis

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    Chen CJ

    2017-11-01

    Full Text Available Chao-Jin Chen,* De-Zhao Liu,* Wei-Feng Yao, Yu Gu, Fei Huang, Zi-Qing Hei, Xiang Li Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Purpose: Neuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL by using bioinformatic analysis.Materials and methods: The microarray profile GSE24982 was downloaded from the Gene Expression Omnibus database to identify DEGs between DRGs in SNL and sham rats. The prioritization for these DEGs was performed using the Toppgene database followed by gene ontology and pathway enrichment analyses. The relationships among DEGs from the protein interactive perspective were analyzed using protein–protein interaction (PPI network and module analysis. Real-time polymerase chain reaction (PCR and Western blotting were used to confirm the expression of DEGs in the rodent neuropathic pain model.Results: A total of 206 DEGs that might play a role in neuropathic pain were identified in L4 DRG, of which 75 were upregulated and 131 were downregulated. The upregulated DEGs were enriched in biological processes related to transcription regulation and molecular functions such as DNA binding, cell cycle, and the FoxO signaling pathway. Ctnnb1 protein had the highest connectivity degrees in the PPI network. The in vivo studies also validated that mRNA and protein levels of Ctnnb1 were

  16. Repetitive Acupuncture Point Treatment with Diluted Bee Venom Relieves Mechanical Allodynia and Restores Intraepidermal Nerve Fiber Loss in Oxaliplatin-Induced Neuropathic Mice.

    Science.gov (United States)

    Yeo, Ji-Hee; Yoon, Seo-Yeon; Kwon, Soon-Keun; Kim, Sol-Ji; Lee, Jang-Hern; Beitz, Alvin J; Roh, Dae-Hyun

    2016-03-01

    The chemotherapeutic agent, oxaliplatin, produces a robust painful neuropathy that results in the loss of intraepidermal nerve fibers (IENFs). We have previously reported that an acupuncture point (acupoint) injection of diluted bee venom (DBV) produces a temporary antiallodynic effect in oxaliplatin-induced neuropathic mice. Herein we show a significant long-lasting antinociceptive effect of repetitive DBV acupoint treatment on oxaliplatin-induced mechanical allodynia and a significant reduction in the loss of IENFs. DBV (0.1 mg/kg, subcutaneous) was administered once a day for 18 days beginning on day 15 after oxaliplatin injection. Immunohistochemistry for IENF was performed on the glabrous skin of the hind paw footpad using the pan-neuronal marker, protein gene product 9.5. A temporary increase in mechanical threshold was observed 60 minutes after a single DBV injection into the Zusanli acupoint, and this effect was enhanced over time with repetitive DBV treatments. The basal mechanical threshold before daily DBV injection also increased from day 7 after DBV injections, and peaked at day 14 after DBV treatment. Moreover, the oxaliplatin-induced loss of IENFs was significantly reduced in mice treated repetitively with DBV. Repetitive pretreatment with the α-2 adrenoceptor antagonist, yohimbine, (5 mg/kg, subcutaneous) completely prevented the antiallodynic effects and the increase in IENFs observed in mice treated repetitively with DBV. We showed that repetitive acupoint stimulation with DBV gradually and significantly reduced oxaliplatin-induced mechanical allodynia and restored the loss of IENFs in neuropathic mice via an α-2 adrenoceptor mechanism. Collectively, results of this study suggest that repetitive acupoint treatment with DBV can be a potential strategy for the management of chemotherapy-induced neuropathy. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  17. Functional brain imaging: what has it brought to our understanding of neuropathic pain? A special focus on allodynic pain mechanisms.

    Science.gov (United States)

    Peyron, Roland

    2016-02-01

    Brain responses to nociception are well identified. The same is not true for allodynic pain, a strong painful sensation in response to touch or innocuous cold stimuli that may be experienced by patients with neuropathic pain. Brain (or spinal cord) reorganization that may explain this paradoxical perception still remains largely unknown. Allodynic pain is associated with abnormally increased activity in SII and in the anterior insular cortex, contralateral and/or ipsilateral to allodynia. Because a bilateral increase in activity has been repeatedly reported in these areas in nociceptive conditions, the observed activation during allodynia can explain that a physiologically nonpainful stimulus could be perceived by the damaged nervous system as a painful one. Both secondary somatosensory and insular cortices receive input from the thalamus, which is a major relay of sensory and spinothalamic pathways, the involvement of which is known to be crucial for the development of neuropathic pain. Both thalamic function and structure have been reported to be abnormal or impaired in neuropathic pain conditions including in the basal state, possibly explaining the spontaneous component of neuropathic pain. A further indication as to how the brain can create neuropathic pain response in SII and insular cortices stems from examples of diseases, including single-case reports in whom a focal brain lesion leads to central pain disappearance. Additional studies are required to certify the contribution of these areas to the disease processes, to disentangle abnormalities respectively related to pain and to deafferentation, and, in the future, to guide targeting of stimulation studies.

  18. Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report

    DEFF Research Database (Denmark)

    Sørensen, Jens Christian Hedemann; Meier, Kaare; Perinpam, Larshan

    Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report......Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report...

  19. MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain.

    Science.gov (United States)

    Wang, Conghui; Jiang, Qi; Wang, Min; Li, Dong

    2015-01-01

    We aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and acetone induced cold allodynia, were performed to evaluate the pain threshold. Besides, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of miR-19a and western blotting was carried out to measure the expression of SOCS1. miR-19a expression levels were markedly increased in neuropathic pain models. Moreover, miR-19a significantly attenuated mechanical allodynia and thermal hyperalgesia, and similar results were obtained after knockdown of SOCS1 expression. However, miR-19a markedly increased the times that the rats appeared a sign of cold allodynia, and knockdown of SOCS1 expression had similar effects. Besides, the results of bioinformatics analysis and western blotting analysis were all confirmed that SOCS1 was a direct target of miR-19a in neuropathic pain models. Our finding indicate that SOCS1 is a direct target of miR-19a in neuropathic pain rats and miR-19a may play a critical role in regulating of neuropathic pain via targeting SOCS1.

  20. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

    Science.gov (United States)

    Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

    2009-04-01

    Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

  1. Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain.

    Science.gov (United States)

    Shibuta, Kazuo; Suzuki, Ikuko; Shinoda, Masamichi; Tsuboi, Yoshiyuki; Honda, Kuniya; Shimizu, Noriyoshi; Sessle, Barry J; Iwata, Koichi

    2012-04-27

    The aim of this study was to evaluate spatial organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1), and to clarify the involvement in mechanisms underlying orofacial secondary hyperalgesia following infraorbital nerve injury. We found that the head-withdrawal threshold to non-noxious mechanical stimulation of the maxillary whisker pad skin was significantly reduced in chronic constriction injury of the infraorbital nerve (ION-CCI) rats from day 1 to day 14 after ION-CCI. On day 3 after ION-CCI, mechanical allodynia was obvious in the orofacial skin areas innervated by the 1st and 3rd branches of the trigeminal nerve as well as the 2nd branch area. Hyperactive microglial cells in Vc and C1 were observed on days 3 and 7 after ION-CCI. On day 3 after ION-CCI, a large number of phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells were observed in Vc and C1. Many hyperactive microglial cells were also distributed over a wide area of Vc and C1 innervated by the trigeminal nerve. The intraperitoneal administration of minocycline significantly reduced the activation of microglial cells and the number of pERK-IR cells in Vc and C1, and also significantly attenuated the development of mechanical allodynia. Furthermore, enhanced background activity and mechanical evoked responses of Vc wide dynamic range neurons in ION-CCI rats were significantly reversed following minocycline administration. These findings suggest that activation of microglial cells over a wide area of Vc and C1 is involved in the enhancement of Vc and C1 neuronal excitability in the early period after ION-CCI, resulting in the neuropathic pain in orofacial areas innervated by the injured as well as uninjured nerves. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. 3D finite element model of the diabetic neuropathic foot: a gait analysis driven approach.

    Science.gov (United States)

    Guiotto, Annamaria; Sawacha, Zimi; Guarneri, Gabriella; Avogaro, Angelo; Cobelli, Claudio

    2014-09-22

    Diabetic foot is an invalidating complication of diabetes that can lead to foot ulcers. Three-dimensional (3D) finite element analysis (FEA) allows characterizing the loads developed in the different anatomical structures of the foot in dynamic conditions. The aim of this study was to develop a subject specific 3D foot FE model (FEM) of a diabetic neuropathic (DNS) and a healthy (HS) subject, whose subject specificity can be found in term of foot geometry and boundary conditions. Kinematics, kinetics and plantar pressure (PP) data were extracted from the gait analysis trials of the two subjects with this purpose. The FEM were developed segmenting bones, cartilage and skin from MRI and drawing a horizontal plate as ground support. Materials properties were adopted from previous literature. FE simulations were run with the kinematics and kinetics data of four different phases of the stance phase of gait (heel strike, loading response, midstance and push off). FEMs were then driven by group gait data of 10 neuropathic and 10 healthy subjects. Model validation focused on agreement between FEM-simulated and experimental PP. The peak values and the total distribution of the pressures were compared for this purpose. Results showed that the models were less robust when driven from group data and underestimated the PP in each foot subarea. In particular in the case of the neuropathic subject's model the mean errors between experimental and simulated data were around the 20% of the peak values. This knowledge is crucial in understanding the aetiology of diabetic foot. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Burning Eye Syndrome: Do Neuropathic Pain Mechanisms Underlie Chronic Dry Eye?

    Science.gov (United States)

    Kalangara, Jerry P; Galor, Anat; Levitt, Roy C; Felix, Elizabeth R; Alegret, Ramon; Sarantopoulos, Constantine D

    2016-04-01

    Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This disorder may also involve neuroplasticity in response to neuronal injury. This review will emphasize the key characteristics of dry eye pain and its pathologic mechanisms, making the argument that a subset of dry eye represents a neuropathic pain disorder of the eye, more appropriately called "burning eye syndrome." A literature review was conducted using a PubMed search focusing on dry eye, corneal nociception, and neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic ocular pain as related to dry eye were summarized. We found that there is a discordance between ocular pain and dryness on the ocular surface. Although tear dysfunction may be one of the initial insults, its persistence may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic pain transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome." © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Percutaneous nerve stimulation in chronic neuropathic pain patients due to spinal cord injury: a pilot study.

    Science.gov (United States)

    Kopsky, David Jos; Ettema, Frank Willem Leo; van der Leeden, Marike; Dekker, Joost; Stolwijk-Swüste, Janneke Marjan

    2014-03-01

    The long-term prognosis for neuropathic pain resolution following spinal cord injury (SCI) is often poor. In many SCI patients, neuropathic pain continues or even worsens over time. Thus, new treatment approaches are needed. We conducted a pilot study to evaluate the feasibility and effect of percutaneous (electrical) nerve stimulation (P(E)NS) in SCI patients with chronic neuropathic pain. In 18 weeks, 12 P(E)NS treatments were scheduled. Assessment with questionnaires was performed at baseline (T0), after 8 weeks (T8), 18 weeks (T18), and 12 weeks post-treatment (T30). From 26 screened patients, 17 were included. In total, 91.2% questionnaires were returned, 2 patients dropped out, and 4.2% of the patients reported minor side effects. Pain scores on the week pain diary measured with the numerical rating scale improved significantly at T8, from 6.5 at baseline to 5.4, and were still significantly improved at T18. Pain reduction of ≥ 30% directly after a session was reported in 64.6% sessions. In total, 6 patients experienced reduction in size of the pain areas at T18 and T30, with a mean reduction of 45.8% at T18 and 45.3% at T30. P(E)NS is feasible as an intervention in SCI patients and might have a positive effect on pain reduction in a part of this patient group. © 2013 The Authors Pain Practice © 2013 World Institute of Pain.

  5. Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.

    Science.gov (United States)

    Patel, Ryan; Dickenson, Anthony H

    2016-07-01

    Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.

  6. Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

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    Alireza Abed

    2017-11-01

    Full Text Available Objective(s: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

  7. APP overexpression prevents neuropathic pain and motoneuron death after peripheral nerve injury in mice.

    Science.gov (United States)

    Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Lewin-Kowalik, Joanna; Paly, Evelyn; London, Jacqueline

    2010-03-16

    Despite general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function and sometimes burdened by neuropathic pain. Amyloid precursor protein (APP) was suggested to play a role in neuronal growth, however, its role in peripheral nerve repair was not studied. The aim of this study was to examine the role of APP overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of APP overexpressing and FVB/N wild-type mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4-week follow up. We found no autotomy behavior as well as less significant atrophy of denervated muscles in APP overexpressing animals when compared to wild-type ones. Sciatic nerve function index outcome did not differ between groups. Histological evaluation revealed that the intensity of regeneration features, including GAP-43-positive growth cones and Schwann cells number in the distal stump of the transected nerve, was also similar in both groups. However, the regenerating fibers were organized more chaotically in wild-type mice and neuromas were much more often seen in this group. The number of macrophages infiltrating the injury site was significantly higher in control group. The number of surviving motoneurons was higher in transgenic mice than in control animals. Taken together, our findings suggest that APP overexpression is beneficial for nerve regeneration processes due to better organization of regenerating fibers, increased survival of motoneurons after autotomy and prevention of neuropathic pain. Copyright 2009 Elsevier Inc. All rights reserved.

  8. Effects of topical Kiwifruit on healing of neuropathic diabetic foot ulcer

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    Gholamreza Mohajeri

    2014-01-01

    Full Text Available Background: Kiwifruit (Actindia Deliciosa is demonstrated to have antibacterial and pro-angiogenic effects. It also contains proteolytic enzymes (actinidin and ascorbic acid. In this study, the effects of Kiwifruit on neuropathic diabetic foot ulcer healing in clinical settings were evaluated. Materials and Methods: In this randomized clinical trial of 37 patients (17 in experimental and 20 in control groups with neuropathic diabetic foot ulcer were studied in Isfahan-Iran. Patients of the control group received just the standard treatments. In the experimental group, in addition to the standard treatments, ulcers were dressed with pure extract of kiwifruit twice daily for 21 days. The ulcers were examined and evaluated based on macroscopic, microscopic and microbiological status. Pre- and post-interventions, biopsies were taken from the ulcers to perform microbiological and histological studies. Results: Mean reduction in surface area of foot ulcer in the experimental group was significantly higher than the control group (168.11 ± 22.31 vs. 88.80 ± 12.04 mm 2 respectively, P < 0.0001. The amount of collagen and granulation tissues was significantly higher in the experimental groups than the control group (P value < 0.0001. Significantly higher levels of angiogenesis and vascularization were found in the kiwifruit treated patients (P value < 0.0001. No significant antibacterial effect was observed for kiwifruit. Conclusion: Natural compounds in the kiwifruit including protein-dissolving enzymes (Actinidin improved different aspects of the wound healing process. Based on these benefits and safety aspects, we conclude that using kiwifruit is a simple, applicable and effective way for treatment of neuropathic diabetic foot ulcer.

  9. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia.

    Science.gov (United States)

    Pfau, Doreen B; Krumova, Elena K; Treede, Rolf-Detlef; Baron, Ralf; Toelle, Thomas; Birklein, Frank; Eich, Wolfgang; Geber, Christian; Gerhardt, Andreas; Weiss, Thomas; Magerl, Walter; Maier, Christoph

    2014-05-01

    Age- and gender-matched reference values are essential for the clinical use of quantitative sensory testing (QST). To extend the standard test sites for QST-according to the German Research Network on Neuropathic Pain-to the trunk, we collected QST profiles on the back in 162 healthy subjects. Sensory profiles for standard test sites were within normal interlaboratory differences. QST revealed lower sensitivity on the upper back than the hand, and higher sensitivity on the lower back than the foot, but no systematic differences between these trunk sites. Age effects were significant for most parameters. Females exhibited lower pressure pain thresholds (PPT) than males, which was the only significant gender difference. Values outside the 95% confidence interval of healthy subjects (considered abnormal) required temperature changes of >3.3-8.2 °C for thermal detection. For cold pain thresholds, confidence intervals extended mostly beyond safety cutoffs, hence only relative reference data (left-right differences, hand-trunk differences) were sufficiently sensitive. For mechanical detection and pain thresholds, left-right differences were 1.5-2.3 times more sensitive than absolute reference data. The most sensitive parameter was PPT, where already side-to-side differences >35% were abnormal. Compared to trunk reference data, patients with postherpetic neuralgia exhibited thermal and tactile deficits and dynamic mechanical allodynia, mostly without reduced mechanical pain thresholds. This pattern deviates from other types of neuropathic pain. QST reference data for the trunk will also be useful for patients with postthoracotomy pain or chronic back pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  10. Cannabinoids and centrak neuropathic pain. A review (Cannabinoidi e dolore neuropatico centrale. Una rassegna

    Directory of Open Access Journals (Sweden)

    Francesco Crestani

    2014-03-01

    Full Text Available Only recently, the medical community highlighted the pharmacological scientific bases of the effects of Cannabis. The most important active principle, Delta-9-tetrahydrocannabinol was identified in the second half of the last century, and receptors were subsequently identified and endogenous ligands, called endocannabinoids, were characterized. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids have shown analgesic properties, particularly interesting with regard to the central neuropathic pain. This article will review the current knowledge and will give practical guidance on how to proceed in prescribing cannabinoids.

  11. Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sagen J

    2016-06-01

    Full Text Available Jacqueline Sagen, Daniel A Castellanos,† Aldric T Hama The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA †Daniel A Castellanos passed away on April 14, 2010 Background: A consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain.Methods: The efficacy of topical anesthetics was evaluated in a preclinical rodent model of painful peripheral neuropathy induced by epineural administration of the HIV envelope protein gp120 delivered using saturated oxidized cellulose implanted around the sciatic nerve. Beginning at 2 weeks following gp120 administration, the effects of local anesthetics topically applied via gauze pads were tested on heat and mechanical hyperalgesia in the hind paw. Rats were tested using several concentrations of mepivacaine or lidocaine during the following 2 weeks.Results: By 2 weeks following epineural gp120 implantation, the ipsilateral hind paw developed significant hypersensitivity to noxious pressure and heat hyperalgesia. A short-lasting, concentration-dependent amelioration of pressure and heat hyperalgesia was observed following topical application of mepivacaine to the ipsilateral plantar hind paw. By contrast, topical lidocaine ameliorated heat hyperalgesia in a concentration-dependent manner but not pressure hyperalgesia. Equipotent concentrations of mepivacaine and lidocaine applied topically to the

  12. Examining the Time to Therapeutic Effect of Pregabalin in Spinal Cord Injury Patients With Neuropathic Pain.

    Science.gov (United States)

    Cardenas, Diana D; Emir, Birol; Parsons, Bruce

    2015-05-01

    In 2 large-scale, placebo-controlled trials, pregabalin improved both pain and pain-related sleep interference in patients with neuropathic pain due to spinal cord injury (SCI). In both trials, pregabalin found statistically significant improvement compared with placebo after 1 week of treatment. However, the effects of pregabalin in the days immediately after initiation of treatment are unknown. The purpose of the present analysis was to determine timing of pregabalin's therapeutic effect in the days after initiation of treatment. Data were derived from 2 trials of pregabalin in patients with SCI-related neuropathic pain. Each day patients rated severity of pain and pain-related sleep interference over the past 24 hours on a scale from 0 to 10, with higher scores indicating greater severity. To quantify timing of therapeutic effect, we compared (pregabalin [vs] placebo) daily average pain and pain-related sleep interference scores over the first 14 days of treatment. Significant improvement was defined as the first day, of ≥2 consecutive days, that pregabalin significantly (P pain and pain-related sleep interference score among patients with a clinically meaningful and sustained response (≥30% improvement from baseline to end point) by using a time-to-event analysis method. Kaplan-Meier analyses were used to estimate the median (or 25th quartile) time (in days) required to achieve a ≥1-point improvement, among these responders, in pain and pain-related sleep interference scores. Comparisons between pregabalin and placebo were made with a log-rank test. In both trials, significant improvement of pain and pain-related sleep interference occurred within 2 days of initiating treatment with pregabalin. Among patients reporting a clinically meaningful and sustained response to treatment (patients with ≥30% improvement from baseline to end point), the time to a ≥1-point improvement of pain and pain-related sleep interference occurred significantly earlier among

  13. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

    OpenAIRE

    Saha, Lekha; Hota, Debasish; Chakrabarti, Amitava

    2012-01-01

    Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel + 0.9% NaCl, Gr III: paclitaxel + lercanidipine 0.5 μg/kg, Gr IV: paclitaxel + lercanidipine 1 μg/kg, and Gr V: paclitaxel + lercanidipine 2.5 μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i....

  14. Role of microglia in neuropathic pain, postoperative pain, and morphine tolerance

    Science.gov (United States)

    Wen, Yeong-Ray; Tan, Ping-Heng; Cheng, Jen-Kun; Liu, Yen-Chin; Ji, Ru-Rong

    2011-01-01

    Management of chronic pain such as nerve injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer is a real clinical challenge. Major surgeries such as breast and thoracic surgery, leg amputation, and coronary artery bypass surgery also lead to chronic pain in 10–50% of individuals after acute postoperative pain, in part due to surgery-induced nerve injury. Current treatments mainly focus on blocking neurotransmission in the pain pathway and have only resulted in limited success. Ironically, chronic opioid exposure may lead to paradoxical pain. Development of effective therapeutic strategies requires a better understanding of cellular mechanisms underlying the pathogenesis of neuropathic pain. An important progress in pain research points to important role of microglial cells in the development of chronic pain. Spinal cord microglia are strongly activated after nerve injury, surgical incision, and chronic opioid exposure. Increasing evidence suggests that under all these conditions the activated microglia not only exhibit increased expression of microglial markers CD11b and Iba1 but also display elevated phosphorylation of p38 MAP kinase. Inhibition of spinal cord p38 has been shown to attenuate neuropathic pain and postoperative pain, as well as morphine-induced antinociceptive tolerance. Activation of p38 in spinal microglia results in increased synthesis and release of the neurotrophin BDNF and the proinflammatory cytokines IL-1β, IL-6, and TNF-α. These microglia-released mediators can powerfully modulate spinal cord synaptic transmission, leading to increased excitability of dorsal horn neurons, i.e. central sensitization, in part via suppressing inhibitory synaptic transmission. We review the studies that support the pronociceptive role of microglia in conditions of neuropathic pain, post-surgical pain, and opioid tolerance. Some of these studies have been accomplished by four Taiwanese anesthesiologists who are also

  15. Microsurgical Drezotomy for Neuropathic Pain after Spinal Cord Injury: Long Term Results in a Patient

    OpenAIRE

    Acevedo González, Juan Carlos; López Cárdenas, Gloria Viviana; Berbeo Calderón, Miguel Enrique; Zorro Guio, Óscar; Díaz Orduz, Roberto Carlos; Feo Lee, Óscar

    2012-01-01

    70 % of patients with spinal cord injuries are chronic and disabling neuropathic pain. This article presents the 23 years-old patient case, who suffered an infrasegmentary severe pain by spinal cord trauma. We performed neurosurgical treatment of pain. Drezotomy is selective section of nociceptive fibers in the spinal segments involved. The patient has 24 months of complete improvement and discontinuation of analgesics. Un 70 % de pacientes con lesión medular tiene dolor neuropático crónic...

  16. Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

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    Hui-Zhong Wen

    2017-06-01

    Full Text Available Background: Transcranial direct current stimulation (tDCS is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters.Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1 on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia.Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI, we measured pain thresholds before and after anodal-tDCS (A-tDCS using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models.Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS and contralateral-tDCS (con-tDCS produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats.Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical

  17. Management of neuropathic pain following treatment for breast cancer in the absence of recurrence: a challenge for the radiation oncologist

    International Nuclear Information System (INIS)

    Clubb, B.

    2004-01-01

    This report reviews various management options for treatment-induced neuropathic pain in breast cancer. First-line options include tricyclic antidepressants and anticonvulsant drugs. Opioids should be prescribed according to published guidelines. Second-line treatments include lignocaine, mexiletine and ketamine. Sympatholytic therapies are available to patients with features of chronic regional pain syndrome. Anti-inflammatory agents are used for neurogenic inflammation. Surgical interventions are considered for refractory neuropathic pain. Interdisciplinary management is appropriate when persisting pain causes physical and psychosocial disabilities. Copyright (2004) Blackwell Science Pty Ltd

  18. Multimodal therapeutic assessment of peripheral nerve stimulation in neuropathic pain: five case reports with a 20-year follow-up

    DEFF Research Database (Denmark)

    Kupers, Ron; Laere, Koen Van; Calenbergh, Frank Van

    2011-01-01

    Neuropathic pain following peripheral nerve lesion is highly resistant to conventional pain treatments but may respond well to direct electrical peripheral nerve stimulation (PNS). In the 1980s, we treated a series of 11 peripheral neuropathic pain patients with PNS. A first outcome assessment......, cool, warmth, cold pain and heat pain thresholds. Laser-evoked potentials showed an enlarged N2-P2 complex during active PNS. Positron Emission Tomography revealed that PNS decreased activation in the pain matrix at rest and during thermal stimulation. PNS led to increased blood flow not only...

  19. MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain

    OpenAIRE

    Wang, Conghui; Jiang, Qi; Wang, Min; Li, Dong

    2015-01-01

    Purpose: we aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. Methods: We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and ace...

  20. Application of the capsaicin 8% cutaneous patch in neuropathic pain of the head and face: A case series.

    Science.gov (United States)

    Gaul, Charly; Resch, Sonja

    2015-05-01

    Treatment of neuropathic or neuralgic head and facial pain due to dental, traumatic or surgical nerve lesions or post-herpetic neuropathy is often challenging. We are reporting on four patients with neuropathic pain syndromes successfully treated with a capsaicin 8% patch in the affected area of the head or face. Treatment with the capsaicin 8% patch seems to be effective and safe for application to the facial and head region. The capsaicin 8% patch might be an additional treatment option if first-line treatment with anticonvulsants or antidepressants was ineffective or limited by side effects. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Footwear for the neuropathic patient: offloading and stability.

    Science.gov (United States)

    van Deursen, Robert

    2008-01-01

    Diabetic neuropathy is related to plantar ulceration through a variety of factors of which increased plantar pressures and loss of protective sensation are the most important. Loss of sensation in the lower limbs is also related to postural instability and an increased risk of falling. Ankle and foot proprioception play an important role in postural control and this sensory function is also affected by neuropathy. It is conceivable that footwear, orthotics, casts and braces used for treatment or prevention of plantar ulceration through offloading of the injured or at-risk foot area can exacerbate the postural instability and risk of falling. This has, however, received very limited attention in the literature. There are studies that have demonstrated that footwear adjustments can influence balance and stability in healthy, elderly subjects. The adjustments made to footwear for the diabetic foot are generally more dramatic and, therefore, are expected to have a greater influence on postural stability. Furthermore, casts and braces tend to deviate even more from normal footwear. This may seriously interfere with normal gait and posture and, therefore, stability. So far the evidence suggests that patients wearing such devices demonstrate markedly reduced activity levels. This reduced activity could add to the effect of offloading. This could also be interpreted to indicate problems with stability. This presentation will review the different types of offloading interventions frequently used for ulcer treatment and prevention and will consider the mechanical effect of these interventions on stability.

  2. Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain.

    Science.gov (United States)

    Sawynok, Jana; Zinger, Celia

    2016-01-01

    Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option. This report summarizes both published and unpublished results of clinical trials with AmiKet. In post-herpetic neuralgia (PHN), AmiKet produces a significant analgesia which is comparable to that produced by oral gabapentin. In diabetic painful neuropathy, AmiKet showed a strong trend towards pain reduction. In mixed neuropathic pain, case series reports suggest a favourable response rate, but are limited by trial characteristics. AmiKet is absorbed minimally following topical administration. Over 700 patients have now received topical AmiKet in clinical regimens, and it is well-tolerated with the adverse effects mainly being application site reactions. Both agents are polymodal, and several mechanisms may contribute to the peripheral efficacy of AmiKet. Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination.

  3. Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy.

    Science.gov (United States)

    Altmann, Christine; Hardt, Stefanie; Fischer, Caroline; Heidler, Juliana; Lim, Hee-Young; Häussler, Annett; Albuquerque, Boris; Zimmer, Béla; Möser, Christine; Behrends, Christian; Koentgen, Frank; Wittig, Ilka; Schmidt, Mirko H H; Clement, Albrecht M; Deller, Thomas; Tegeder, Irmgard

    2016-12-01

    Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confirmed in primary sensory neurons. Autophagy and survival were impaired in progranulin-deficient neurons and improved in progranulin overexpressing neurons. Nerve injury in vivo caused an accumulation of LC3b-EGFP positive bodies in neurons of the dorsal root ganglia and nerves suggesting an impairment of autophagic flux. Overexpression of progranulin in these neurons was associated with a reduction of the stress marker ATF3, fewer protein aggregates in the injured nerve and enhanced stump healing. At the behavioral level, further inhibition of the autophagic flux by hydroxychloroquine intensified cold and heat nociception after sciatic nerve injury and offset the pain protection provided by progranulin. We infer that progranulin may assist in removal of protein waste and thereby helps to resolve neuropathic pain after nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Longitudinal Structural and Functional Brain Network Alterations in a Mouse Model of Neuropathic Pain.

    Science.gov (United States)

    Bilbao, Ainhoa; Falfán-Melgoza, Claudia; Leixner, Sarah; Becker, Robert; Singaravelu, Sathish Kumar; Sack, Markus; Sartorius, Alexander; Spanagel, Rainer; Weber-Fahr, Wolfgang

    2018-04-22

    Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery. A progressive development and potentiation of stimulus-evoked pain responses (cold and mechanical allodynia) were detected during the course of pain chronification. Voxel-based morphometry demonstrated striking decreases in volume following pain induction in all brain sites assessed - an effect that reversed over time. Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Use of high performance technologies in the treatment of chronic neuropathic pain

    Directory of Open Access Journals (Sweden)

    Streltov Ion

    2018-03-01

    Full Text Available Spinal cord neurostimulation is a minimally invasive treatment method for chronic neuropathic pain that is refractory to treatment, and is part of top technology in field. Relatively recent introduction of this method in the Neurosurgery Clinic “Prof. Dr. N. Oblu” of Iasi has aligned the clinic’s therapeutic arsenal to world standards. This has made it possible to treat in Romania a category of patients who would be treated abroad until now. Our clinic has entered the “National Program for diagnostic and treatment using high performance equipment” - Subprogram of treatment of neuropathic pain by implant of a spinal cord neurostimulator and is currently the only one in Romania where this treatment can be done. This represents a new step in the transformation process of the Clinical Hospital Emergency “Prof. Dr. N. Oblu” Iasi in a real Center of Excellence in the field Neurosurgery. The team dealing with the implant consists of 3 neurosurgeons, a neurologist, pa sychologist and an anesthetist, trained in a specialized foreign center.

  6. The management of neuropathic ulcers of the foot in diabetes by shock wave therapy

    Directory of Open Access Journals (Sweden)

    Pascone Michele

    2009-05-01

    Full Text Available Abstract Background Diabetes is becoming one of the most common chronic diseases, and ulcers are its most serious complication. Beginning with neuropathy, the subsequent foot wounds frequently lead to lower extremity amputation, even in the absence of critical limb ischemia. In recent years, some researchers have studied external shock wave therapy (ESWT as a new approach to soft tissue wound healing. The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers. Methods We designed a randomized, prospective, controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies. One group was treated with standard care and shock wave therapy. The other group was treated with only standard care. The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization. Results After 20 weeks of treatment, 53.33% of the ESWT-treated patients had complete wound closure compared with 33.33% of the control patients, and the healing times were 60.8 and 82.2 days, respectively (p 2/die in the ESWT-group and 1.30 mm2/die in the control group (p Conclusion Therefore, ESWT may be a useful adjunct in the management of diabetic foot ulceration. Trial registration Current Controlled Trials ISRCTN21800909

  7. A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

    2016-01-01

    The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

  8. The Effect of Repeated Electroacupuncture Analgesia on Neurotrophic and Cytokine Factors in Neuropathic Pain Rats

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    Junying Wang

    2016-01-01

    Full Text Available Chronic pain is a common disability influencing quality of life. Results of previous studies showed that acupuncture has a cumulative analgesic effect, but the relationship with spinal cytokines neurotrophic factors released by astrocytes remains unknown. The present study was designed to observe the effect of electroacupuncture (EA treatment on spinal cytokines neurotrophic factors in chronic neuropathic pain rats. The chronic neuropathic pain was established by chronic constrictive injury (CCI. EA treatment was applied at Zusanli (ST36 and Yanglingquan (GB34 (both bilateral once a day, for 30 min. IL-1β mRNA, TNF-α mRNA, and IL-1 mRNA were detected by quantitative real-time PCR, and the proteins of BDNF, NGF, and NT3/4 were detected by Western blot. The expression levels of cytokines such as IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, and neurotrophic factors such as BDNF, NGF, and NT3/4 in the spinal cord were increased significantly after CCI. The astrocytes released more IL-1β and BDNF after CCI. Repeated EA treatment could suppress the elevated expression of IL-1β mRNA, TNFα mRNA, and BDNF, NGF, and NT3/4 but had no effect on IL-6 mRNA. It is suggested that cytokines and neurotrophic factors which may be closely associated with astrocytes participated in the process of EA relieving chronic pain.

  9. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

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    Woojin Kim

    2016-01-01

    Full Text Available Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.. BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36 or morphine (0.5, 2, and 5 mg/kg, i.p. alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg or 5-HT3 (MDL-72222, 15 μg receptor antagonist, but not with α2-adrenergic (idazoxan, 10 μg receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.

  10. Sensory Symptom Profiles of Patients With Neuropathic Pain After Spinal Cord Injury.

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    Soler, Maria Dolors; Moriña, David; Rodríguez, Neus; Saurí, Joan; Vidal, Joan; Navarro, Albert; Navarro, Xavier

    2017-09-01

    Individuals experiencing neuropathic pain (NP) after spinal cord injury (SCI) present with a variety of pain descriptors in different combinations and at different intensities. These sensory features form distinct patterns, known as sensory symptom profiles. In the present cross-sectional study, we have used a multivariate statistical method (multiple correspondence analysis) to categorize the sensory symptom profiles of a cohort of 338 patients with at-level or below-level NP after SCI. We also investigated possible associations between positive neuropathic symptoms and features of the neurological lesion. The majority of participants had a combination of pain descriptors, with 59% presenting with 3 or 4 pain subtypes. No significant associations were found between specific pain profiles and etiology or clinical degree of the neurological lesion. Furthermore, similar symptom profiles were seen in patients with at-level and below-level NP. The most frequent pattern observed in patients with cervical SCI consisted predominantly of electric shocks and tingling, without burning, pressure pain, or allodynia. Classification of SCI-NP patients into the 5 groups identified in the present study based on their distinct sensory symptom profiles may allow identification of those most likely to respond to a specific analgesic approach.

  11. Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex

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    Ruohe Zhao

    2018-04-01

    Full Text Available The anterior cingulate cortex (ACC is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5 pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.

  12. Preventive Effects of Bee Venom Derived Phospholipase A₂ on Oxaliplatin-Induced Neuropathic Pain in Mice.

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    Li, Dongxing; Kim, Woojin; Shin, Dasom; Jung, Yongjae; Bae, Hyunsu; Kim, Sun Kwang

    2016-01-19

    Oxaliplatin, a chemotherapy drug used to treat colorectal cancer, induces specific sensory neurotoxicity signs that are aggravated by cold and mechanical stimuli. Here we examined the preventive effects of Bee Venom (BV) derived phospholipase A₂ (bvPLA₂) on oxaliplatin-induced neuropathic pain in mice and its immunological mechanism. The cold and mechanical allodynia signs were evaluated by acetone and von Frey hair test on the hind paw, respectively. The most significant allodynia signs were observed at three days after an injection of oxaliplatin (6 mg/kg, i.p.) and then decreased gradually to a normal level on days 7-9. The oxaliplatin injection also induced infiltration of macrophages and upregulated levels of the pro-inflammatory cytokine interleukin (IL)-1β in the lumbar dorsal root ganglia (DRG). Daily treatment with bvPLA₂ (0.2 mg/kg, i.p.) for five consecutive days prior to the oxaliplatin injection markedly inhibited the development of cold and mechanical allodynia, and suppressed infiltration of macrophages and the increase of IL-1β level in the DRG. Such preventive effects of bvPLA₂ were completely blocked by depleting regulatory T cells (Tregs) with CD25 antibody pre-treatments. These results suggest that bvPLA₂ may prevent oxaliplatin-induced neuropathic pain by suppressing immune responses in the DRG by Tregs.

  13. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice.

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    Kim, Woojin; Kim, Min Joon; Go, Donghyun; Min, Byung-Il; Na, Heung Sik; Kim, Sun Kwang

    2016-01-22

    Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2 adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.

  14. The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

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    Li Li

    2010-05-01

    Full Text Available Abstract Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p ® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0% subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601

  15. Fear of pain in children and adolescents with neuropathic pain and CRPS

    Science.gov (United States)

    Simons, Laura E.

    2015-01-01

    A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Due to faulty nerve signaling, individuals with neuropathic pain and CRPS may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to down-regulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, while high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear as well as evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with CRPS suggest breakthroughs in our ability to ameliorate these issues. PMID:26785161

  16. Fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome.

    Science.gov (United States)

    Simons, Laura E

    2016-02-01

    A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Because of faulty nerve signaling, individuals with neuropathic pain and complex regional pain syndrome may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to downregulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, whereas high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear and evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with complex regional pain syndrome suggest breakthroughs in our ability to ameliorate these issues.

  17. Alterations in the Anandamide Metabolism in the Development of Neuropathic Pain

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    Natalia Malek

    2014-01-01

    Full Text Available Endocannabinoids (EC, particularly anandamide (AEA, released constitutively in pain pathways might be accountable for the inhibitory effect on nociceptors. Pathogenesis of neuropathic pain may reflect complex remodeling of the dorsal root ganglia (DRGs and spinal cord EC system. Multiple pathways involved both in the biosynthesis and degradation of AEA have been suggested. We investigated the local synthesis and degradation features of AEA in DRGs and spinal cord during the development and maintenance of pain in a model of chronic constriction injury (CCI. All AEA synthesis and degradation enzymes are present on the mRNA level in DRGs and lumbar spinal cord of intact as well as CCI-treated animals. Deregulation of EC system components was consistent with development of pain phenotype at days 3, 7, and 14 after CCI. The expression levels of enzymes involved in AEA degradation was significantly upregulated ipsilateral in DRGs and spinal cord at different time points. Expression of enzymes of the alternative, sPLA2-dependent and PLC-dependent, AEA synthesis pathways was elevated in both of the analyzed structures at all time points. Our data have shown an alteration of alternative AEA synthesis and degradation pathways, which might contribute to the variation of AEA levels and neuropathic pain development.

  18. Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

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    Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

    2018-05-31

    Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. In contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared to sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.

  19. Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models

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    Kanako So

    2015-03-01

    Full Text Available Recent evidence suggests a role of transient receptor potential melastatin 2 (TRPM2 in immune and inflammatory responses. We previously reported that TRPM2 deficiency attenuated inflammatory and neuropathic pain in some pain mouse models, including formalin- or carrageenan-induced inflammatory pain, and peripheral nerve injury-induced neuropathic pain models, while it had no effect on the basal mechanical and thermal nociceptive sensitivities. In this study, we further explored the involvement of TRPM2 in various pain models using TRPM2-knockout mice. There were no differences in the chemonociceptive behaviors evoked by intraplantar injection of capsaicin or hydrogen peroxide between wildtype and TRPM2-knockout mice, while acetic acid-induced writhing behavior was significantly attenuated in TRPM2-knockout mice. In the postoperative incisional pain model, no difference in mechanical allodynia was observed between the two genotypes. By contrast, mechanical allodynia in the monosodium iodoacetate-induced osteoarthritis pain model and the experimental autoimmune encephalomyelitis model were significantly attenuated in TRPM2-knockout mice. Furthermore, mechanical allodynia in paclitaxel-induced peripheral neuropathy and streptozotocin-induced painful diabetic neuropathy models were significantly attenuated in TRPM2-knockout mice. Taken together, these results suggest that TRPM2 plays roles in a wide range of pathological pain models based on peripheral and central neuroinflammation, rather than physiological nociceptive pain.

  20. Motor cortex stimulation in the treatment of central and neuropathic pain.

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    Nguyen, J P; Lefaucher, J P; Le Guerinel, C; Eizenbaum, J F; Nakano, N; Carpentier, A; Brugières, P; Pollin, B; Rostaing, S; Keravel, Y

    2000-01-01

    Motor cortex stimulation has been proposed for the treatment of central pain. Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated on according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated on by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organization of the motor cortex was established preoperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and 10 of the 12 patients with neuropathic facial pain experienced substantial pain relief (83.3%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. Our results confirm that chronic stimulation of the motor cortex is an effective method in treating certain forms of refractory pain.

  1. Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.

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    Xi-Tuan Ji

    Full Text Available Chemotherapy-induced neuropathic pain (CNP is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor; whereas minocycline (microglial specific inhibitor had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

  2. Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

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    Mert, Tufan; Kurt, Akif Hakan; Altun, İdiris; Celik, Ahmet; Baran, Furkan; Gunay, Ismail

    2017-05-01

    Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Mitogen activated protein kinase phosphatase-1 prevents the development of tactile sensitivity in a rodent model of neuropathic pain

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    Ndong Christian

    2012-04-01

    Full Text Available Abstract Background Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. Results We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide. Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced pro-inflammatory cytokines and chemokines and the phosphorylated form of p38. Conclusions Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.

  4. Nanoparticle-Encapsulated Curcumin Inhibits Diabetic Neuropathic Pain Involving the P2Y12 Receptor in the Dorsal Root Ganglia

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    Tianyu Jia

    2018-01-01

    Full Text Available Diabetic peripheral neuropathy results in diabetic neuropathic pain (DNP. Satellite glial cells (SGCs enwrap the neuronal soma in the dorsal root ganglia (DRG. The purinergic 2 (P2 Y12 receptor is expressed on SGCs in the DRG. SGC activation plays an important role in the pathogenesis of DNP. Curcumin has anti-inflammatory and antioxidant properties. Because curcumin has poor metabolic stability in vivo and low bioavailability, nanoparticle-encapsulated curcumin was used to improve its targeting and bioavailability. In the present study, our aim was to investigate the effects of nanoparticle-encapsulated curcumin on DNP mediated by the P2Y12 receptor on SGCs in the rat DRG. Diabetic peripheral neuropathy increased the expression levels of the P2Y12 receptor on SGCs in the DRG and enhanced mechanical and thermal hyperalgesia in rats with diabetes mellitus (DM. Up-regulation of the P2Y12 receptor in SGCs in the DRG increased the production of pro-inflammatory cytokines. Up-regulation of interleukin-1β (IL-1β and connexin43 (Cx43 resulted in mechanical and thermal hyperalgesia in rats with DM. The nanoparticle-encapsulated curcumin decreased up-regulated IL-1β and Cx43 expression and reduced levels of phosphorylated-Akt (p-Akt in the DRG of rats with DM. The up-regulation of P2Y12 on SGCs and the up-regulation of the IL-1β and Cx43 in the DRG indicated the activation of SGCs in the DRG. The nano-curcumin treatment inhibited the activation of SGCs accompanied by its anti-inflammatory effect to decrease the up-regulated CGRP expression in the DRG neurons. Therefore, the nanoparticle-encapsulated curcumin treatment decreased the up-regulation of the P2Y12 receptor on SGCs in the DRG and decreased mechanical and thermal hyperalgesia in rats with DM.

  5. Can gradual dose titration of ketamine for management of neuropathic pain prevent psychotomimetic effects in patients with advanced cancer?

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    Okamoto, Yoshiaki; Tsuneto, Satoru; Tanimukai, Hitoshi; Matsuda, Yoichi; Ohno, Yumiko; Tsugane, Mamiko; Uejima, Etsuko

    2013-08-01

    Ketamine is often used to manage neuropathic pain in patients with cancer. However, it occasionally causes psychotomimetic effects such as vivid dreams, nightmares, illusions, hallucinations, and altered body image. To examine whether gradual dose titration of ketamine for management of neuropathic pain prevents psychotomimetic effects in patients with advanced cancer. This was a retrospective chart review. We administered ketamine when neuropathic pain in patients with advanced cancer became refractory to opioids and oral adjuvant analgesics. The starting dose of ketamine was 10 mg/d by continuous intravenous infusion. The dose was gradually increased by 10 mg/d every 4 to 6 hours to 50 mg/d or until the pain was relieved. It was subsequently increased by 25 mg/d every 12 to 24 hours until the pain was relieved. For this study, we enrolled 46 patients with advanced cancer. The mean age was 52.2 ± 16.9 years. The mean dose at onset of action and maximum dose of ketamine were 56 ± 58 and 272 ± 214 mg/d, respectively. The mean pain intensity (numerical rating scale) decreased significantly from 7.3 ± 2.0 to 3.5 ± 2.2 after the administration of ketamine (P ketamine for management of neuropathic pain can prevent psychotomimetic effects in patients with advanced cancer.

  6. Effect of injury on S1 dorsal root ganglia in an experimental model of neuropathic faecal incontinence.

    LENUS (Irish Health Repository)

    Peirce, C

    2011-08-01

    An experimental model of neuropathic faecal incontinence has recently been established. This study aimed to quantify and compare the effect of crush and compression injury on first-order sensory neurones of the inferior rectal nerve (IRN) using a nuclear marker of axonal injury, activating transcription factor (ATF) 3.

  7. Modulation of Invading and Resident Inflammatory Cell Activation as a Novel Way to Mitigate Spinal Cord Injury Associated Neuropathic Pain

    Science.gov (United States)

    2016-10-01

    shown by the FDA in the determination of its full range of therapeutic benefits. Tlmeline and Cost Activities Aim 1 Effect of CBD on SCI- NP ...the non-psychoactive cannabinoid cannabidiol (CBD) on spinal cord injury neuropathic pain (SCI- NP ) and associated lnllammation. Changes in thermal and...1 4. Impact ........................................................................... 13 5. Changes/ Problems

  8. Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

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    Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

    2016-01-01

    One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

  9. The effect of low-frequency TENS in the treatment of neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Celik, E C; Erhan, B; Gunduz, B; Lakse, E

    2013-04-01

    Prospective, randomized and controlled study. The aim of the study was to investigate the effect of low-frequency transcutaneous electrical nerve stimulation (LF-TENS) in the treatment of neuropathic pain in patients with spinal cord injury (SCI). A total of 33 SCI patients with neuropathic pain were included in the study. History, duration, localization and characteristics of pain were recorded. Visual analog scale (VAS) was used to investigate the effect of LF-TENS four times during the day. Patients were randomly assigned to study and control groups. The study group was treated with 30 min of LF-TENS daily for 10 days while the placebo group with 30 min of sham TENS. The mean age of the patients was 36.55±10.36 years. Out of 33 patients, 7 were tetraplegic and 26 were paraplegic. Twenty-three patients had complete SCI while 10 patients had incomplete injuries. Two groups were similar with respect to age, gender, duration, level and severity of injury. In the LF-TENS treatment group, a statistically significant reduction of the VAS values was observed, however, such an effect was not evident in the control group. This study revealed that in treatment of neuropathic pain of SCI patients, LF-TENS may be effective. This article presents LF-TENS may effectively complement pharmacological treatment in patients with SCI and neuropathic pain.

  10. Tumor necrosis factor-alpha is a potential diagnostic biomarker for chronic neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Xu, Jun; E, Xiaoqiang; Liu, Huiyong; Li, Feng; Cao, Yanhui; Tian, Jun; Yan, Jinglong

    2015-05-19

    Neuropathic pain (NP) is one of the most common complications after spinal cord injury (SCI), but no protein biomarkers has ever been introduced into clinical diagnosis. Previous studies implicated that toll-like receptor (TLR) 4 played a critical role in the development of NP in animal SCI models. Here, a total of 140 participants were recruited, 70 of them were SCI-NP subject and the rest 70 controls did not show neuropathic symptoms. TLR4 was upregulated significantly in SCI-NP patients compared with SCI-noNP subjects. Furthermore, we measured the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), two TLR4 downstream pro-inflammatory cytokines, to assess their diagnostic values. Receiver operating characteristics (ROC) analysis revealed that TNF-α had great potential advantages to predict the progression of neuropathy, the risks of NP were strongly increased in SCI subjects with higher levels of TNF-α (odds ratio: 4.92; 95% confidence interval: 1.89-12.32). These results suggested neuro-immune activation contributed to the development of neuropathic disorder after SCI, and TNF-α could be a potential sensitive diagnostic biomarker for chronic neuropathic pain in SCI patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Capsaicin 8% Patch for Central and Peripheral Neuropathic Pain of Persons with Incomplete Spinal Cord Injury: Two Case Reports.

    Science.gov (United States)

    Trbovich, Michelle; Yang, Huiqing

    2015-08-01

    Neuropathic pain after spinal cord injury is common and often refractory to standard treatments. The capsaicin 8% patch is a Food and Drug Administration-approved treatment of neuropathic pain in postherpetic neuralgia and has demonstrated significant efficacy in human immunodeficiency virus-autonomic neuropathy. The patch defunctionalizes transient receptor potential vanilloid 1 receptors, impairing cutaneous nociceptors for a prolonged period (i.e., 8-12 wks) with no systemic side effects. A retrospective review was conducted on the effects of the patch in two patients with spinal cord injury and neuropathic pain refractory to standard treatments. Two weeks after application, both patients reported complete pain relief. Average onset of relief of 4 days and average duration of relief of 197 days, requiring only one to four applications per year, paralleled findings reported in postherpetic neuralgia and human immunodeficiency virus-autonomic neuropathy trials. Upregulation of capsaicin-sensitive transient receptor potential vanilloid 1 receptors after spinal cord injury has been reported. The capsaicin 8% patch is a promising therapeutic agent for neuropathic pain in spinal cord injury.

  12. Prolonged Suppression of Neuropathic Pain by Sequential Delivery of Lidocaine and Thalidomide Drugs Using PEGylated Graphene Oxide.

    Science.gov (United States)

    Song, Tieying; Gu, Kunfeng; Wang, Wenli; Wang, Hong; Yang, Yunliang; Yang, Lijun; Ma, Pengxu; Ma, Xiaojing; Zhao, Jianhui; Yan, Ruyu; Guan, Jiao; Wang, Chunping; Qi, Yan; Ya, Jian

    2015-11-01

    The management of patients with neuropathic pain is challenging. Monotherapy with a single pain relief drug may encounter different difficulties, such as short duration of efficacy and hence too many times of drug administration, and inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have been proved to provide promising strategies for efficient drug loading, delivery, and release. In the present study, we developed poly(ethylene glycol) methyl ether functionalized graphene oxide (GO) bearing two commonly used drugs of lidocaine (LDC) and thalidomide (THD) as an agent for the treatment of neuropathic pain. The sequential drug release of LDC and THD from the developed LDC-THD-GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro and in vivo, as evidenced by the increased pain threshold in mechanical allodynia and hyperalgesic response tests, and the improved inhibition of proinflammatory cytokines TNF-α, IL-1β, IL-6, and nitric oxide. We believed that the present study herein would hold promise for future development of a new generation of potent agents for neuropathic pain relief. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  13. A comparison of coping strategies in patients with fibromyalgia, chronic neuropathic pain, and pain-free controls

    DEFF Research Database (Denmark)

    Baastrup, Sidsel; Schultz, Rikke; Brødsgaard, Inger

    2016-01-01

    different groups of chronic pain patients and a group of healthy controls. Thirty neuropathic pain (NP) patients, 28 fibromyalgia (FM) patients, and 26 pain-free healthy controls completed the Coping Strategy Questionnaire (CSQ-48/27) and rated their daily pain. The results showed that FM and NP patients...

  14. Experienced dilemmas of everyday life in chronic neuropathic pain patients--results from a critical incident study.

    Science.gov (United States)

    Hensing, Gunnel K E; Sverker, Annette M; Leijon, Göran S

    2007-06-01

    Neuropathic pain is a disabling chronic condition with limited therapeutic options. Few studies have addressed patient's experience and strategies. The aim of this study was to explore dilemmas experienced in order to improve care and rehabilitation. An interview study with 39 patients suffering from neuropathic pain of different origin was performed. We used the critical incident technique to collect data. Questions on occasions when patients had been hindered by or reminded of their neuropathic pain were included, and the self-perceived consequences and management of such occasions. The interviews were transcribed verbatim and analysed qualitatively. A broad range of experiences categorised into dilemmas, disturbances, consequences and managements from most parts of everyday life was identified. The dilemmas were 'housework', 'sitting', 'physical activity', 'personal hygiene', 'sleeping difficulties', 'hypersensitivity to external stimuli', 'social relationships', 'transportation' and 'leisure time'. Disturbances were 'failures', 'inabilities' and 'restrictions'. Consequences were 'increased pain', 'psychological reactions' and 'physical symptoms'. The majority of the patients used activity-oriented strategies to manage their pain such as alternative ways of performing the task, a cognitive approach or simply ignoring the pain. This is one of the first studies presenting detailed data on everyday dilemmas, disturbances and consequences of patients with chronic neuropathic pain. Such information is important in clinical settings to improve care and rehabilitation.

  15. Executive summary of the Clinical Guidelines of Pharmacotherapy for Neuropathic Pain: second edition by the Japanese Society of Pain Clinicians.

    Science.gov (United States)

    Sumitani, Masahiko; Sakai, Tetsuya; Matsuda, Yoichi; Abe, Hiroaki; Yamaguchi, Shigeki; Hosokawa, Toyoshi; Fukui, Sei

    2018-06-01

    Neuropathic pain has a substantial effect on quality of life (QOL). The Japanese Society of Pain Clinicians (JSPC) has developed clinical guidelines of pharmacotherapy for neuropathic pain. These guidelines offer clarity on recommendations based on both the most recent scientific evidence and expert opinions. Understanding the concept, disease entity, and burden of neuropathic pain, as well as its screening and diagnosis are important steps before starting pharmacotherapy. As well as other guidelines, the guidelines propose several lines of pharmacotherapies in a step-wise manner. To name a few different points, our guidelines propose an extract from inflamed cutaneous tissue of rabbits inoculated with vaccinia virus, which has been found to be effective for post-herpetic neuralgia in Japan, as one of the second-line drugs. When prescribing opioid analgesics, proposed as the third-line drugs, for neuropathic pain, the guidelines recommend physicians continue evaluations on either abuse or addiction. The guidelines do not recommend concomitant use of nonsteroidal anti-inflammatory drugs and acetaminophen because of lack of clinical evidence of their efficacy. If patients do not respond well to pharmacotherapy, which is prescribed in a step-wise manner, other treatment strategies should be considered to improve patients' activities of daily living and QOL.

  16. Continuous brachial plexus block at the cervical level using a posterior approach in the management of neuropathic cancer pain

    NARCIS (Netherlands)

    Vranken, J. H.; van der Vegt, M. H.; Zuurmond, W. W.; Pijl, A. J.; Dzoljic, M.

    2001-01-01

    Neuropathic cancer pain due to tumor growth near the brachial plexus is often treated with a combination of nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, anticonvulsants, and oral or transdermal opioids. We propose placement of a catheter along the brachial plexus using a

  17. Topical gabapentin gel alleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury neuropathic pain model.

    Science.gov (United States)

    Shahid, M; Subhan, F; Ahmad, N; Ali, G; Akbar, S; Fawad, K; Sewell, R D E

    2017-04-01

    Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic-mechano-allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat- (PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery. Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes. Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the

  18. Long non-coding RNA CCAT1 modulates neuropathic pain progression through sponging miR-155.

    Science.gov (United States)

    Dou, Lidong; Lin, Hongqi; Wang, Kaiwei; Zhu, Guosong; Zou, Xuli; Chang, Enqiang; Zhu, Yongfeng

    2017-10-27

    Neuropathic pain is caused by dysfunction or primary injury of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) play important roles in the development of neuropathic pain. However, the effects of lncRNA colon cancer associated transcript-1 (CCAT1) in neuropathic pain have not been reported. The model of bilateral sciatic nerve chronic constriction injuries (bCCI) is regarded as long-lasting mechanical hypersensitivity and cold allodynia, which is the representative symptom in the human subjects suffering from the neuropathic pain. In this study, we found that CCAT1 expression was decreased in the spinal dorsal horn, dorsal root ganglion (DRG), hippocampus, and anterior cingulate cortex (ACC) of rats with bCCI. The rats of bCCI presented the cold allodynia after the 14 th day of postoperation. We furtherly showed that lncRNA CCAT1 decreased miR-155 expression and enhanced Serum and glucocorticoid regulated protein kinase 3 (SGK3) expression in the NGF-differentiated PC12 cell. We found that miR-155 expression was increased in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. However, SGK3 expression was downregulated in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. Moreover, lncRNA CCAT1 overexpression could alleviate the pain thresholds and inhibited expression of SGK3 could rescue this effect. In conclusion, these results suggested the crucial roles of CCAT1 and SGK3 in the neuropathic pain.

  19. Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: a review.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Leis, Stefan; Höller, Peter; Thon, Natasha; Thomschewski, Aljoscha; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2014-01-01

    Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain. To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy. A MEDLINE search was performed using following terms: "Spinal cord injury", "Neuropathic pain", "Brain stimulation", "Deep brain stimulation" (DBS), "Motor cortex stimulation" (MCS), "Transcranial magnetic stimulation" (TMS), "Transcranial direct current stimulation" (tDCS), "Cranial electrotherapy stimulation" (CES). Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation - tDCS - applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI. A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.

  20. Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis.

    Science.gov (United States)

    Lind, Anne-Li; Emami Khoonsari, Payam; Sjödin, Marcus; Katila, Lenka; Wetterhall, Magnus; Gordh, Torsten; Kultima, Kim

    2016-08-01

    Electrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. Two different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. Eighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). Previously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain. © 2016 International Neuromodulation Society.

  1. Initial accuracy assessment of the modified S-LANSS for the detection of neuropathic orofacial pain conditions.

    Science.gov (United States)

    Herrero Babiloni, Alberto; Nixdorf, Donald R; Law, Alan S; Moana-Filho, Estephan J; Shueb, Sarah S; Nguyen, Ruby H; Durham, Justin

    2017-01-01

    To evaluate the accuracy of a questionnaire modified for the identification of intraoral pain with neuropathic characteristics in a clinical orofacial pain sample population. 136 participants with at least one of four orofacial pain diagnoses (temporomandibular disorders [TMD, n = 41], acute dental pain [ADP, n = 41], trigeminal neuralgia [TN, n = 19], persistent dentoalveolar pain disorder [PDAP, n = 14]) and a group of pain-free controls (n = 21) completed the modified S-LANSS, a previously adapted version of the original questionnaire devised to detected patients suffering from intraoral pain with neuropathic characteristics. Psychometric properties (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) were calculated in two analyses with two different thresholds: (1) Detection of pain with neuropathic characteristics: PDAP + TN were considered positive, and TMD + ADP + controls were considered negative per gold standard (expert opinion). (2) Detection of PDAP: PDAP was considered positive and TMD + ADP were considered negative per gold standard. For both analyses, target values for adequate sensitivity and specificity were defined as ≥ 80%. For detection of orofacial pain with neuropathic characteristics (PDAP + TN), the modified S-LANSS presented with the most optimistic threshold sensitivity of 52% (95% confidence interval [CI], 34-69), specificity of 70% (95% CI, 60-79), PPV of 35% (95% CI, 22-51), and NPV of 82% (95% CI, 72-89). For detection of PDAP only, with the most optimistic threshold sensitivity was 64% (95% CI, 35-87), specificity 63% (95% CI, 52-74), PPV 23% (95% CI, 11-39) and NPV 91% (95% CI, 81-97). Based on a priori defined criteria, the modified S-LANSS did not show adequate accuracy to detect intraoral pain with neuropathic characteristics in a clinical orofacial pain sample.

  2. Evaluation of the Effect of Duration on the Efficacy of Pulsed Radiofrequency in an Animal Model of Neuropathic Pain.

    Science.gov (United States)

    Ramzy, Eiad A; Khalil, Khaled I; Nour, Eman M; Hamed, Mohammed F; Taha, Mohamed A

    2018-03-01

    Pulsed radiofrequency (PRF) is increasingly used in clinical practice, especially in neuropathic pain disorders. Although PRF is not new to clinical use, there are significant gaps in knowledge regarding its effectiveness. The current study was conducted to evaluate the effect of duration of application of PRF on its analgesic efficacy in improvement of neuropathic pain. A randomized experimental trial. An animal research facility at the College of Veterinary Medicine at Mansoura University in Egypt. Chronic constriction of the sciatic nerve of 36 male Sprague-Dawley rats was performed to induce neuropathic pain. The rats were divided into 6 groups (6 rats each) in which PRF was applied for 2, 4, 6, or 8 minutes or not at all. In one group, RF cannula was applied without performing PRF intervention. The pain was assessed through observation of resting paw posture (RPP) at 3, 10, and 21 days. Nerve damage was assessed by histopathological evaluation of the sciatic nerve. Immunohistochemical localization of proinflammatory cytokines (interleukin 6 [IL-6] and tumor necrosis factor alpha [TNF-alpha]) was also done. RPP was improved in rats treated with PRF. This improvement was significant only in rats treated for 8 minutes. Increased duration for PRF application was associated with a significant decrease in IL-6 and TNF-alpha contents in all groups when compared with the control group. Histopathological evaluation of the constricted sciatic nerve revealed no statistical significance among the different study groups. The study was limited by the lack of measurement of other inflammatory markers that may help elucidate other relevant mechanisms. Increased duration of PRF application resulted in better analgesic efficacy