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  1. Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction

    OpenAIRE

    Flatters, Sarah J.L.; Bennett, Gary J.

    2006-01-01

    Paclitaxel chemotherapy frequently induces neuropathic pain during and often persisting after therapy. The mechanisms responsible for this pain are unknown. Using a rat model of paclitaxel-induced painful peripheral neuropathy, we have performed studies to search for peripheral nerve pathology. Paclitaxel-induced mechano-allodynia and mechano-hyperalgesia were evident after a short delay, peaked at day 27 and finally resolved on day 155. Paclitaxel- and vehicle-treated rats were perfused on d...

  2. Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

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    Mehmet Fidanboylu

    Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

  3. Global Inhibition of Reactive Oxygen Species (ROS) Inhibits Paclitaxel-Induced Painful Peripheral Neuropathy

    OpenAIRE

    Fidanboylu, Mehmet; Griffiths, Lisa A.; Flatters, Sarah J. L.

    2011-01-01

    Paclitaxel (Taxol (R)) is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS...

  4. CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

    Science.gov (United States)

    Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

    2014-08-01

    Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.

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    Laurence Meyer

    Full Text Available Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in

  6. Pharmacological Modulation of the Mitochondrial Electron Transport Chain in Paclitaxel-Induced Painful Peripheral Neuropathy.

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    Griffiths, Lisa A; Flatters, Sarah J L

    2015-10-01

    Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive

  7. Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

    OpenAIRE

    Kiya, T; Kawamata, T; Namiki, A; Yamakage, M

    2011-01-01

    Paclitaxel is one of the most commonly used antineoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involveme...

  8. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

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    Kuniaki Tsutsumi; Takanori Kaname; Haruka Shiraishi; Takehiro Kawashiri; Nobuaki Egashira

    2016-01-01

    Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7) and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect th...

  9. Cold therapy to prevent paclitaxel-induced peripheral neuropathy.

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    Griffiths, Claire; Kwon, Nancy; Beaumont, Jennifer L; Paice, Judith A

    2018-04-21

    This case-control study was designed to assess the efficacy of cryotherapy to prevent paclitaxel-induced painful peripheral neuropathy in women with breast cancer. Participants served as their own paired control, with randomization of the cooled glove/sock to either the dominant or the non-dominant hand/foot, worn for 15 min prior to, during, and 15 min after completion of the paclitaxel infusion. Outcome measures included the Neuropathic Pain Symptom Inventory, the Brief Pain Inventory, and quantitative sensory testing. Data were measured at each of six time points-baseline, post-treatment (approximately 2 weeks after the last paclitaxel infusion), and at the first, fifth, ninth, and final weekly paclitaxel treatments. Of 29 randomized participants, 20 (69%) received at least one cryotherapy treatment, and 11 (38%) received all four cryotherapy treatments. Ten (34%) participants could not tolerate the cryotherapy, and six (21%) declined further participation at some point during the trial. Only seven participants (24%) were available for the final post-chemotherapy QST and questionnaires. There were no significant differences in measures of neuropathy or pain between treated and untreated hands or feet. Strategies to prevent painful peripheral neuropathy are urgently needed. In this current trial, dropout due to discomfort precluded adequate power to fully understand the potential benefits of cryotherapy. Much more research is needed to discover safe and effective preventive strategies that can be easily implemented within busy infusion centers.

  10. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

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    Kuniaki Tsutsumi

    2016-06-01

    Full Text Available Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7 and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor-bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy.

  11. Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFκB phosphorylation in spinal cord of mice.

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    Junzo Kamei

    Full Text Available Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB in the spinal dorsal horn. Rikkunshito (RKT, a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB.

  12. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy

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    Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

    2015-01-01

    Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P neuropathy (P peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449

  13. 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 ...

  14. 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.

  15. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

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    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....

  16. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment

    OpenAIRE

    Mo, Michelle; Erdelyi, Ildiko; Szigeti-Buck, Klara; Benbow, Jennifer H.; Ehrlich, Barbara E.

    2012-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that occurs in many patients undergoing chemotherapy. It is often irreversible and frequently leads to early termination of treatment. In this study, we have identified two compounds, lithium and ibudilast, that when administered as a single prophylactic injection prior to paclitaxel treatment, prevent the development of CIPN in mice at the sensory-motor and cellular level. The prevention of neuropathy was not obs...

  17. Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral neuropathy in mice.

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    Sayeli, Vijaykumar; Nadipelly, Jagan; Kadhirvelu, Parimala; Cheriyan, Binoy Varghese; Shanmugasundaram, Jaikumar; Subramanian, Viswanathan

    2018-04-13

    Peripheral neuropathy is the dose limiting side effect of many anticancer drugs. Flavonoids exhibit good antinociceptive effect in animal models. Their efficacy against different types of nociception has been documented. The present study investigated the effect of flavonol (3-hydroxy flavone), 3',4'-dimethoxy flavonol, 6,3'-dimethoxy flavonol, 7,2'-dimethoxy flavonol and 7,3'-dimethoxy flavonol against paclitaxel-induced peripheral neuropathy in mice. A single dose of paclitaxel (10 mg/kg, i.p.) was administered to induce peripheral neuropathy in mice and the manifestations of peripheral neuropathy such as tactile allodynia, cold allodynia and thermal hyperalgesia were assessed 24 h later by employing Von Frey hair aesthesiometer test, acetone bubble test and hot water tail immersion test, respectively. The test compounds were prepared as a suspension in 0.5% carboxymethyl cellulose and were administered s.c. in various doses (25, 50, 100 and 200 mg/kg). The above behavioral responses were assessed prior to and 30 min after drug treatment. In addition, the effect of test compounds on proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and free radicals was investigated by using suitable in vitro assays. A dose-dependent attenuation of tactile allodynia, cold allodynia and thermal hyperalgesia was evidenced in mice treated with flavonol derivatives. The test compounds inhibited TNF-α, IL-1β and free radicals in a concentration-dependent manner. These results revealed that flavonol and its dimethoxy derivatives ameliorated the manifestations of paclitaxel-induced peripheral neuropathy in mice. The inhibition of proinflammatory cytokines and free radicals could contribute to this beneficial effect.

  18. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

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    Lekha Saha

    2012-01-01

    Full Text Available 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.p. injection of 1 mg/kg of paclitaxel on four alternate days (0, 2, 4, and 6. The tail flick and cold allodynia methods were used for assessing the pain threshold, and the assessments were done on days 0 (before first dose of paclitaxel and on days 7, 14, 21, and 28. Results. There was a significant decrease (P<0.001 in the tail flick and cold allodynia latency in the paclitaxel-alone group from day 14 onward when compared with day 0. In the lercanidipine groups, the decrease in the tail flick and cold allodynia latency was not observed in 1.0 and 2.5 μg/kg groups and it was statistically significant (P<0.01 when compared with paclitaxel-alone group.

  19. Evidence that spinal astrocytes but not microglia contribute to the pathogenesis of paclitaxel-induced painful neuropathy

    OpenAIRE

    Zhang, Haijun; Yoon, Seo-Yeon; Zhang, Hongmei; Dougherty, Patrick M.

    2012-01-01

    Paclitaxel often induces persistent painful neuropathy as its most common treatment limiting side effect. Little is known concerning the underlying mechanisms. Given the prominent role of glial cells in many types of neuropathic pain, we investigated here the morphological and functional changes of spinal astrocytes and microglia in a rat model of paclitaxel-induced neuropathy. Immunohistochemistry, western blotting and real-time polymerase chain reaction (rt-PCR) were performed with samples ...

  20. A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways.

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    Janes, Kali; Esposito, Emanuela; Doyle, Timothy; Cuzzocrea, Salvatore; Tosh, Dillip K; Jacobson, Kenneth A; Salvemini, Daniela

    2014-12-01

    Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. We recently reported that activation of the Gi/Gq-coupled A3 adenosine receptor (A3AR) with selective A3AR agonists (ie, IB-MECA) blocked the development of chemotherapy induced-neuropathic pain evoked by distinct agents, including paclitaxel, without interfering with anticancer effects. The mechanism or mechanisms of action underlying these beneficial effects has yet to be explored. We now demonstrate that IB-MECA attenuates the development of paclitaxel-induced neuropathic pain by inhibiting the activation of spinal NADPH oxidase and two downstream redox-dependent systems. The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy. Copyright © 2014

  1. Preventative and therapeutic effects of a GABA transporter 1 inhibitor administered systemically in a mouse model of paclitaxel-induced neuropathic pain

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    Willias Masocha

    2016-12-01

    Full Text Available Background There is a dearth of drugs to manage a dose-limiting painful peripheral neuropathy induced by paclitaxel in some patients during the treatment of cancer. Gamma-aminobutyric acid transporter-1 (GAT-1 whose expression is increased in the brain and spinal cord during paclitaxel-induced neuropathic pain (PINP might be a potential therapeutic target for managing PINP. Thus, our aim was to evaluate if systemic administration of a GAT-1 inhibitor ameliorates PINP. Methods The reaction latency to thermal stimuli (hot plate test; at 55 °C and cold stimuli (cold plate test; at 4 °C of female BALB/c mice was recorded before and after intraperitoneal treatment with paclitaxel, its vehicle, and/or a selective GAT-1 inhibitor NO-711. The effects of NO-711 on motor coordination were evaluated using the rotarod test at a constant speed of 4 rpm or accelerating mode from 4 rpm to 40 rpm over 5 min. Results The coadministration of paclitaxel with NO-711 3 mg/kg prevented the development of paclitaxel-induced thermal hyperalgesia and cold allodynia at day 7 after drug treatment. NO-711 at 3 mg/kg produced antihyperalgesic activity up to 1 h and antiallodynic activity up to 2 h in mice with established paclitaxel-induced thermal hyperalgesia and cold allodynia. No motor deficits were observed with NO-711 at a dose of 3 mg/kg, whereas a higher dose 5 mg/kg caused motor impairment and reduced mean time spent on the rotarod at a constant speed of 4 rpm. However, at a rotarod accelerating mode from 4 rpm to 40 rpm over 5 min, NO-711 3 mg/kg caused motor impairment up to 1 h, but had recovered by 2 h. Conclusions These results show that systemic administration of the GAT-1 inhibitor NO-711 has preventative and therapeutic activity against paclitaxel-induced thermal hyperalgesia and cold allodynia. NO-711’s antiallodynic effects, but not antihyperalgesic effects, were independent of its motor impairment/sedation properties. Thus, low doses of GAT-1

  2. DRG Voltage-Gated Sodium Channel 1.7 Is Upregulated in Paclitaxel-Induced Neuropathy in Rats and in Humans with Neuropathic Pain.

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    Li, Yan; North, Robert Y; Rhines, Laurence D; Tatsui, Claudio Esteves; Rao, Ganesh; Edwards, Denaya D; Cassidy, Ryan M; Harrison, Daniel S; Johansson, Caj A; Zhang, Hongmei; Dougherty, Patrick M

    2018-01-31

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Na v 1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Na v 1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Na v 1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Na v 1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Na v 1.7 associated with spontaneous activity. Na v 1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Na v 1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain. SIGNIFICANCE STATEMENT This work demonstrates that the expression and function of the voltage-gated sodium channel Na

  3. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial

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    Ghoreishi Zohreh

    2012-08-01

    Full Text Available Abstract Background Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. Methods This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN. Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". Results Twenty one patients (70% of the group taking omega-3 fatty acid supplement (n = 30 did not develop PN while it was 40.7%( 11 patients in the placebo group(n = 27. A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88, p = 0.029. There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (−2.06 -0.02, p = 0.054. Conclusions Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients’ quality of life. Trial registration This trial was registered at ClinicalTrials.gov (NCT01049295

  4. Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α₂-Adrenergic Receptor.

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    Choi, Jiho; Jeon, Changhoon; Lee, Ji Hwan; Jang, Jo Ung; Quan, Fu Shi; Lee, Kyungjin; Kim, Woojin; Kim, Sun Kwang

    2017-10-31

    Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α₂-adrenergic receptor antagonist (idazoxan, 50 µg), but not α₁-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α₂-adrenergic receptor.

  5. Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor

    Directory of Open Access Journals (Sweden)

    Jiho Choi

    2017-10-01

    Full Text Available Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal on four alternate days (days 0, 2, 4, and 6 induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36 relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36 and phospholipase A2 (0.12 mg/kg, ST36 were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg, but not α1-adrenergic receptor antagonist (prazosin, 30 µg, blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor.

  6. Minoxidil is a potential neuroprotective drug for paclitaxel-induced peripheral neuropathy

    Science.gov (United States)

    Chen, Yi-Fan; Chen, Li-Hsien; Yeh, Yu-Min; Wu, Pei-Ying; Chen, Yih-Fung; Chang, Lian-Yun; Chang, Jang-Yang; Shen, Meng-Ru

    2017-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. No medication has been shown to be effective in the treatment of CIPN. This study aims to integrate the image-based high-content screening, mouse behavior models and mechanistic cell-based assays to discover potential neuroprotective drugs. Among screened compounds, minoxidil showed the most potent neuroprotective effect against paclitaxel, with regard to neurite outgrowth of dorsal root ganglia (DRG). Minoxidil protected mice from thermal insensitivity and alleviated mechanical allodynia in paclitaxel-treated mice. The ultrastructure and quantified G-ratio of myelin integrity of sciatic nerve tissues supported the observations in mouse behavioral tests. The mechanistic study on DRG neurons suggested that minoxidil suppressed neuroinflammation and remodeled the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, minoxidil showed a synergistic anti-tumor effect with paclitaxel both in tumor xenograft models of cervical and breast cancer. Interestingly, the quantitative assays on hair length and hair growth both exhibited that minoxidil significantly improved the hair quality after chemotherapy. Since minoxidil is a drug approved by the Food and Drug Administration (FDA), the safety and biocompatibility are well documented. The immediate next step is to launch an early-stage clinical trial intending to prevent CIPN by minoxidil. PMID:28349969

  7. Prevention of Paclitaxel-induced allodynia by Minocycline: Effect on loss of peripheral nerve fibers and infiltration of macrophages in rats

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    Xin Wen-Jun

    2010-11-01

    Full Text Available Abstract Background Although paclitaxel is a frontline antineoplastic agent for treatment of solid tumors, the paclitaxel-evoked pain syndrome is a serious problem for patients. There is currently no valid drug to prevent or treat the paclitaxel-induced allodynia, partly due to lack of understanding regarding the cellular mechanism. Studies have shown that minocycline, an inhibitor of microglia/macrophage, prevented neuropathic pain and promoted neuronal survival in animal models of neurodegenerative disease. Recently, Cata et al also reported that minocycline inhibited allodynia induced by low-dose paclitaxel (2 mg/kg in rats, but the mechanism is still unclear. Results Here, we investigate by immunohistochemistry the change of intraepidermal nerve fiber (IENF in the hind paw glabrous skin, expression of macrophage and activating transcription factor 3 (ATF3 in DRG at different time points after moderate-dose paclitaxel treatment (cumulative dose 24 mg/kg; 3 × 8 mg/kg in rats. Moreover, we observe the effect of minocycline on the IENF, macrophages and ATF3. The results showed that moderate-dose paclitaxel induced a persisted, gradual mechanical allodynia, which was accompanied by the loss of IENF in the hind paw glabrous skin and up-regulation of macrophages and ATF3 in DRG in rats. The expressions of ATF3 mainly focus on the NF200-positive cells. More importantly, we observed that pretreatment of minocycline at dose of 30 mg/kg or 50 mg/kg, but not 5 mg/kg, prevented paclitaxel-evoked allodynia. The evidence from immunohistochemistry showed that 30 mg/kg minocycline rescued the degeneration of IENF, attenuated infiltration of macrophages and up-regulation of ATF3 induced by paclitaxel treatment in rats. Conclusions Minocycline prevents paclitaxel-evoked allodynia, likely due to its inhibition on loss of IENF, infiltration of macrophages and up-regulation of ATF3 in rats. The finding might provide potential target for preventing paclitaxel-induced

  8. Targeted sequencing reveals low-frequency variants in EPHA genes as markers of paclitaxel-induced peripheral neuropathy.

    OpenAIRE

    Apellániz-Ruiz, Maria; Tejero, Héctor; Inglada-Pérez, Lucía; Sánchez-Barroso, Lara; Gutiérrez-Gutiérrez, Gerardo; Calvo, Isabel; Castelo, Beatriz; Redondo, Andrés; García-Donás, Jesus; Romero-Laorden, Nuria; Sereno, Maria; Merino, María; Currás-Freixes, Maria; Montero-Conde, Cristina; Mancikova, Veronika

    2017-01-01

    PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes. EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes invo...

  9. A proof-of-concept trial of protein kinase C iota inhibition with auranofin for the paclitaxel-induced acute pain syndrome.

    Science.gov (United States)

    Jatoi, Aminah; Grudem, Megan E; Dockter, Travis J; Block, Matthew S; Villasboas, Jose C; Tan, Angelina; Deering, Erin; Kasi, Pashtoon M; Mansfield, Aaron S; Botero, Juliana Perez; Okuno, Scott H; Smith, Deanne R; Fields, Alan P

    2017-03-01

    Paclitaxel causes the paclitaxel-induced acute pain (PIAP) syndrome. Based on preclinical data, we hypothesized that the protein kinase C (PKC) iota inhibitor, auranofin (a gold salt used for other pain conditions), palliates this pain. In a randomized, double-blinded manner, patients who had suffered this syndrome were assigned a one-time dose of auranofin 6 mg orally on day #2 of the chemotherapy cycle (post-paclitaxel) versus placebo. Patients completed the Brief Pain Inventory and a pain diary on days 2 through 8 and at the end of the cycle. The primary endpoint was pain scores, as calculated by area under the curve, in response to "Please rate your pain by circling the one number that best describes your pain at its worse in the last 24 hours." Thirty patients were enrolled. For the primary endpoint, mean area under the curve of 55 units (standard deviation 19) and 61 units (standard deviation 22) were observed in auranofin-treated and placebo-exposed patients, respectively (p = 0.44). On day 8 and at the end of the cycle, pain scores in auranofin-treated patients were more favorable, although differences were not statistically significant. In the dose schedule studied, auranofin did not palliate the PIAP syndrome, but delayed beneficial trends suggest further study for this indication.

  10. Gene expression profile of sodium channel subunits in the anterior cingulate cortex during experimental paclitaxel-induced neuropathic pain in mice

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    Willias Masocha

    2016-11-01

    Full Text Available Paclitaxel, a chemotherapeutic agent, causes neuropathic pain whose supraspinal pathophysiology is not fully understood. Dysregulation of sodium channel expression, studied mainly in the periphery and spinal cord level, contributes to the pathogenesis of neuropathic pain. We examined gene expression of sodium channel (Nav subunits by real time polymerase chain reaction (PCR in the anterior cingulate cortex (ACC at day 7 post first administration of paclitaxel, when mice had developed paclitaxel-induced thermal hyperalgesia. The ACC was chosen because increased activity in the ACC has been observed during neuropathic pain. In the ACC of vehicle-treated animals the threshold cycle (Ct values for Nav1.4, Nav1.5, Nav1.7, Nav1.8 and Nav1.9 were above 30 and/or not detectable in some samples. Thus, comparison in mRNA expression between untreated control, vehicle-treated and paclitaxel treated animals was done for Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nax as well as Navβ1–Navβ4. There were no differences in the transcript levels of Nav1.1–Nav1.3, Nav1.6, Nax, Navβ1–Navβ3 between untreated and vehicle-treated mice, however, vehicle treatment increased Navβ4 expression. Paclitaxel treatment significantly increased the mRNA expression of Nav1.1, Nav1.2, Nav1.6 and Nax, but not Nav1.3, sodium channel alpha subunits compared to vehicle-treated animals. Treatment with paclitaxel significantly increased the expression of Navβ1 and Navβ3, but not Navβ2 and Navβ4, sodium channel beta subunits compared to vehicle-treated animals. These findings suggest that during paclitaxel-induced neuropathic pain (PINP there is differential upregulation of sodium channels in the ACC, which might contribute to the increased neuronal activity observed in the area during neuropathic pain.

  11. Management of paclitaxel-induced neurotoxicity

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    Manisha Bhutani

    2011-12-01

    Full Text Available Paclitaxel exerts its antitumor activity by promoting microtubule assembly and stabilizing microtubules. Microtubules are important for the development and maintenance of neurons. As a consequence, neurotoxicity is one of the drug’s major side effects. The risk of neurotoxicity depends on dose, duration and schedule of paclitaxel. Risk increases for patients with pre-existing conditions that may cause neuropathy (such as alcohol consumption, diabetes, or renal disease or with simultaneous or prior exposure to other neurotoxic chemotherapy such as platinum-based drugs, vinca alkaloids, immunomodulators, proteasome inhibitors, and epothilones. Patients with paclitaxel-induced neurotoxicity (PINT experience a constellation of symptoms over the course of treatment and beyond, ranging from mild to severe. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. Proprioceptive and motor effects become apparent as neuropathy becomes more advanced. These symptoms may be prolonged, severe, disabling, relatively resistant to intervention and adversely affect activities of daily living and thereby quality of life. Management is mainly symptomatic and supportive. Despite attempts to minimize PINT with changes in dose, vehicle, delivery systems, infusion schedule and premedication or co-treatment with neuroprotective agents, PINT remains dose-limiting in many instances and is a barrier to achieving the desired clinical response.

  12. Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in paclitaxel-induced mechanical allodynia

    OpenAIRE

    Ochi-ishi, Ryutaro; Nagata, Kenichiro; Inoue, Tomoyuki; Tozaki-Saitoh, Hidetoshi; Tsuda, Makoto; Inoue, Kazuhide

    2014-01-01

    Background Paclitaxel is an effective chemotherapeutic agent widely used for the treatment of solid tumors. The major dose-limiting toxicity of paclitaxel is peripheral neuropathy. The mechanisms underlying the development and maintenance of paclitaxel-induced peripheral neuropathy are still unclear, and there are no currently established effective treatments. Accumulating evidence in models of neuropathic pain in which peripheral nerves are lesioned has implicated spinal microglia and chemok...

  13. Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel

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    Muh. Akbar Bahar

    2013-01-01

    Full Text Available Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of commonly used chemotherapeutic agents. However, there are no effective strategies to treat the neuropathy. We examined whether Goshajinkigan, a herbal medicine, would prevent paclitaxel-induced allodynia without affecting the anticancer action in mice. Murine breast cancer 4T1 cells were inoculated into the mammary fat pad. Paclitaxel (10 and 20 mg/kg, intraperitoneal, alternate day from day 7 postinoculation inhibited the tumor growth, and Goshajinkigan (1 g/kg, oral, daily from day 2 postinoculation did not affect the antitumor action of paclitaxel. Mechanical allodynia developed in the inoculated region due to tumor growth and in the hind paw due to paclitaxel-induced neuropathy. Paclitaxel-induced allodynia was markedly prevented by Goshajinkigan, although tumor-associated allodynia was not inhibited by Goshajinkigan. These results suggest that Goshajinkigan prevents paclitaxel-induced peripheral neuropathy without interfering with the anti-cancer action of paclitaxel.

  14. Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

    Science.gov (United States)

    Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

    2018-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT(1A) receptors without diminishing nervous system function or chemotherapy efficacy.

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    Ward, Sara Jane; McAllister, Sean D; Kawamura, Rumi; Murase, Ryuchi; Neelakantan, Harshini; Walker, Ellen A

    2014-02-01

    Paclitaxel (PAC) is associated with chemotherapy-induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD) prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy. The ability of acute CBD pretreatment to prevent PAC-induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant-conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay. PAC-induced mechanical sensitivity was prevented by administration of CBD (2.5 - 10 mg·kg⁻¹) in female C57Bl/6 mice. This effect was reversed by co-administration of the 5-HT(1A) antagonist WAY 100635, but not the CB₁ antagonist SR141716 or the CB₂ antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability. Our data suggest that CBD is protective against PAC-induced neurotoxicity mediated in part by the 5-HT(1A) receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC-induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN. © 2013 The British Pharmacological Society.

  16. Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy

    Science.gov (United States)

    Ward, Sara Jane; McAllister, Sean D; Kawamura, Rumi; Murase, Ryuchi; Neelakantan, Harshini; Walker, Ellen A

    2014-01-01

    Background and Purpose Paclitaxel (PAC) is associated with chemotherapy-induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD) prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy. Experimental Approach The ability of acute CBD pretreatment to prevent PAC-induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant-conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay. Key Results PAC-induced mechanical sensitivity was prevented by administration of CBD (2.5 – 10 mg·kg−1) in female C57Bl/6 mice. This effect was reversed by co-administration of the 5-HT1A antagonist WAY 100635, but not the CB1 antagonist SR141716 or the CB2 antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability. Conclusions and Implications Our data suggest that CBD is protective against PAC-induced neurotoxicity mediated in part by the 5-HT1A receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC-induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN. PMID:24117398

  17. Ionic mechanisms in peripheral pain.

    Science.gov (United States)

    Fransén, Erik

    2014-01-01

    Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs. © 2014 Elsevier Inc. All rights reserved.

  18. Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel

    OpenAIRE

    Bahar, Muh. Akbar; Andoh, Tsugunobu; Ogura, Keisuke; Hayakawa, Yoshihiro; Saiki, Ikuo; Kuraishi, Yasushi

    2013-01-01

    Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of commonly used chemotherapeutic agents. However, there are no effective strategies to treat the neuropathy. We examined whether Goshajinkigan, a herbal medicine, would prevent paclitaxel-induced allodynia without affecting the anticancer action in mice. Murine breast cancer 4T1 cells were inoculated into the mammary fat pad. Paclitaxel (10 and 20 mg/kg, intraperitoneal, alternate day from day 7 postinoculation) ...

  19. Treatment of painful diabetic peripheral neuropathy.

    Science.gov (United States)

    Rosenberg, Casandra J; Watson, James C

    2015-02-01

    Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.

  20. The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB2 receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Deng Liting

    2012-09-01

    Full Text Available Abstract Background Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone CB2 agonist, produces antinociception without producing central nervous system (CNS-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel. A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4 signaling to both chemotherapy-induced neuropathy and CB2 agonist efficacy. Results AM1710 (0.1, 1 or 5 mg/kg i.p. suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB2 antagonist AM630 (3 mg/kg i.p., but not the CB1 antagonist AM251 (3 mg/kg i.p., consistent with a CB2-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p. failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action. Conclusions Our results indicate that activation of cannabinoid CB2 receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB2 receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents.

  1. Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy.

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    Raghav Sundar

    Full Text Available Sensory peripheral neuropathy caused by paclitaxel is a common and dose limiting toxicity, for which there are currently no validated predictive biomarkers. We investigated the relationship between the Charcot-Marie-Tooth protein NDRG1 and paclitaxel-induced neuropathy.Archived mammary tissue specimen blocks of breast cancer patients who received weekly paclitaxel in a single centre were retrieved and NDRG1 immunohistochemistry was performed on normal nerve tissue found within the sample. The mean nerve NDRG1 score was defined by an algorithm based on intensity of staining and percentage of stained nerve bundles. NDRG1 scores were correlated with paclitaxel induced neuropathy.111 patients were studied. 17 of 111 (15% developed severe paclitaxel-induced neuropathy. The mean nerve NDRG1 expression score was 5.4 in patients with severe neuropathy versus 7.7 in those without severe neuropathy (p = 0.0019. A Receiver operating characteristic (ROC curve analysis of the mean nerve NDRG1 score revealed an area under the curve of 0.74 (p = 0.0013 for the identification of severe neuropathy, with a score of 7 being most discriminative. 13/54 (24% subjects with an NDRG1 score 7 (p = 0.017.Low NDRG1 expression in nerve tissue present within samples of surgical resection may identify subjects at risk for severe paclitaxel-induced neuropathy. Since nerve biopsies are not routinely feasible for patients undergoing chemotherapy for early breast cancer, this promising biomarker strategy is compatible with current clinical workflow.

  2. Peripherally applied opioids for postoperative pain

    DEFF Research Database (Denmark)

    Nielsen, B N; Henneberg, S W; Schmiegelow, K

    2015-01-01

    BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June...... 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity...... difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved...

  3. Peripheral changes in endometriosis-associated pain

    Science.gov (United States)

    Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

    2014-01-01

    BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between

  4. Contrast media and pain during peripheral arteriography

    International Nuclear Information System (INIS)

    Hagen, B.; Clauss, W.

    1982-01-01

    Some contrast media (CM) were for inducing pain and heat by an intraindividual comparison in 60 patients with occlusive peripheral arterial disease. A dolorimeter and calorimeter (graduated scales) were employed to register and differentiate the subjective sensations experienced by the patient, while objective reactions (peripheral motoric reactions, circulatory parameters) were recorded by the trialist at the same time. Ioxaglate, an ionic dimer, was distinctly superior to Ioglicinate, an ionic CM. However, the differences were less marked in the comparison with a Ioglicinate-Lidocaine-mixture. Emphasis is given to the fact osmolality is the most important parameter in the development of pain. Potential points at which the intraarterially administered local anaesthetic could attack are discussed. The clinical conclusions include consideration of the cost-effectivity ratios of the tested CM's and a discussion of whether or not modern stanards still justify general anaesthesia for peripheral angiography. (orig.)

  5. Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish.

    Science.gov (United States)

    Lisse, Thomas S; Middleton, Leah J; Pellegrini, Adriana D; Martin, Paige B; Spaulding, Emily L; Lopes, Olivia; Brochu, Elizabeth A; Carter, Erin V; Waldron, Ashley; Rieger, Sandra

    2016-04-12

    Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up-regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions.

  6. 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...

  7. Trichloropropane and dichlorohydrin associated with painful peripheral neurotoxicity.

    Science.gov (United States)

    Shi, Xiaobing; Yu, Shengyuan

    2013-10-01

    Trichloropropane (TCP) and dichlorohydrin are widely used in industrial production; however, TCP and dichlorohydrin poisoning are rarely encountered in clinical practice. There have been no cases of peripheral neurotoxicity previously reported. A cluster of 23 patients who had been exposed to high levels of TCP and dichlorohydrin presented with painful peripheral neuropathy, and the pain was assessed using a visual analogue scale (VAS). Nerve conduction studies (NCS) were performed in all patients. All patients demonstrated symmetrical pin-prick pain in a stocking distribution in the lower limbs, with VAS scores between 3 and 10, with an average score of 6.8. NCS showed a mild mixture of axonal and demyelinating sensorimotor polyneuropathy in 14 of the 23 patients. After administration of standard neuropathic pain medication, pain was relieved in most patients. Painful peripheral neuropathy was the primary symptom observed in our patients, which differs from clinical and animal model reports of TCP or dichlorohydrin poisoning. However, the pathogenesis remains unidentified. TCP may be added to the list of industrial products that are toxic to the peripheral sensory nerves. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Science.gov (United States)

    2010-04-01

    ....5870 Implanted peripheral nerve stimulator for pain relief. (a) Identification. An implanted peripheral nerve stimulator for pain relief is a device that is used to stimulate electrically a peripheral nerve... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted peripheral nerve stimulator for pain...

  9. 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...

  10. 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.

  11. Evidence of peripheral nerve blocks for cancer-related pain

    DEFF Research Database (Denmark)

    Klepstad, P; Kurita, G P; Mercadante, S

    2015-01-01

    The European Association for Palliative Care has initiated a comprehensive program to achieve an over-all review of the evidence of multiple cancer pain management strategies in order to extend the current guideline for treatment of cancer pain. The present systematic review analyzed the existing...... evidence of analgesic efficacy for peripheral nerve blocks in adult patients with cancer. A search strategy was elaborated with words related to cancer, pain, peripheral nerve and block. The search was performed in PubMed, EMBASE, and Cochrane for the period until February 2014. The number of abstracts...... retrieved was 155. No controlled studies were identified. Sixteen papers presented a total of 79 cases. The blocks applied were paravertebral blocks (10 cases), blocks in the head region (2 cases), plexus blocks (13 cases), intercostal blocks (43 cases) and others (11 cases). In general, most cases reported...

  12. Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy

    OpenAIRE

    Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J.

    2011-01-01

    Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicati...

  13. 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

  14. Assessment of paclitaxel induced sensory polyneuropathy with "Catwalk" automated gait analysis in mice.

    Directory of Open Access Journals (Sweden)

    Petra Huehnchen

    Full Text Available Neuropathic pain as a symptom of sensory nerve damage is a frequent side effect of chemotherapy. The most common behavioral observation in animal models of chemotherapy induced polyneuropathy is the development of mechanical allodynia, which is quantified with von Frey filaments. The data from one study, however, cannot be easily compared with other studies owing to influences of environmental factors, inter-rater variability and differences in test paradigms. To overcome these limitations, automated quantitative gait analysis was proposed as an alternative, but its usefulness for assessing animals suffering from polyneuropathy has remained unclear. In the present study, we used a novel mouse model of paclitaxel induced polyneuropathy to compare results from electrophysiology and the von Frey method to gait alterations measured with the Catwalk test. To mimic recently improved clinical treatment strategies of gynecological malignancies, we established a mouse model of dose-dense paclitaxel therapy on the common C57Bl/6 background. In this model paclitaxel treated animals developed mechanical allodynia as well as reduced caudal sensory nerve action potential amplitudes indicative of a sensory polyneuropathy. Gait analysis with the Catwalk method detected distinct alterations of gait parameters in animals suffering from sensory neuropathy, revealing a minimized contact of the hind paws with the floor. Treatment of mechanical allodynia with gabapentin improved altered dynamic gait parameters. This study establishes a novel mouse model for investigating the side effects of dose-dense paclitaxel therapy and underlines the usefulness of automated gait analysis as an additional easy-to-use objective test for evaluating painful sensory polyneuropathy.

  15. Stimulation of the peripheral nervous system for pain control.

    Science.gov (United States)

    Long, D M

    1983-01-01

    Transcutaneous stimulation is a proven effective way to relieve pain. Its optimal use requires an accurate patient diagnosis. Treatment of pain as a symptom only is likely to fail. There must be a careful psychosocial evaluation, for the majority of patients who come to the doctor complaining of pain have major psychological, social, or behavioral factors that are most important in the genesis of the complaint. Drug abuse must be corrected. Related symptoms, such as anxiety and depression, must be treated. Then, a thorough trail of transcutaneous stimulation is mandatory. A desultory use will undoubtedly lead to failure. This trial must begin with patient education by experienced personnel. Then the electrodes must be properly applied, and there must be a regular follow-up of stimulation to be certain the patient is utilizing it correctly. The patient must be supported through an adequate trial which should extend over 2-4 weeks before purchase of the device is contemplated. Furthermore, all related nursing and physician personnel must be educated in the proper use of the technique. The uninformed professional who denigrates the therapy is a very effective deterrent to appropriate use. In this situation, transcutaneous electrical stimulation will be of great value in the treatment of acute musculoskeletal injury and acute postoperative pain. It will be effective in the treatment of peripheral nerve injury pain, chronic musculoskeletal abnormalities, chronic pain in the patient who has undergone multiple operations upon the low back and neck, visceral pain, some of the reflex sympathetic dystrophies, and postherpetic neuralgia. Stimulation will not help a complaint which is psychosomatic in origin. It will not influence drug addiction. It is not likely to be useful in any situation where secondary gain is important. The metabolic neuropathies, pain of spinal cord injury, and pain from cerebrovascular accident will not respond frequently enough to warrant more than

  16. Origin of pain in migraine: evidence for peripheral sensitisation

    DEFF Research Database (Denmark)

    Olesen, Jes; Burstein, Rami; Ashina, Messoud

    2009-01-01

    , in our view, neuronal hyperexcitability depends on activation of peripheral nociceptors. Although the onset of a migraine attack might take place in deep-brain structures, some evidence indicates that the headache phase depends on nociceptive input from perivascular sensory nerve terminals. The input......Migraine is the most common neurological disorder, and much has been learned about its mechanisms in recent years. However, the origin of painful impulses in the trigeminal nerve is still uncertain. Despite the attention paid recently to the role of central sensitisation in migraine pathophysiology...

  17. 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...

  18. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  19. 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

  20. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-01-01

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis. PMID:24549172

  1. Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory

    Directory of Open Access Journals (Sweden)

    Zhao Li

    2018-01-01

    Full Text Available The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1β in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function.

  2. Trigeminal pain and quantitative sensory testing in painful peripheral diabetic neuropathy.

    Science.gov (United States)

    Arap, Astrid; Siqueira, Silvia R D T; Silva, Claudomiro B; Teixeira, Manoel J; Siqueira, José T T

    2010-07-01

    To evaluate patients with Diabetes Mellitus type 2 and painful peripheral neuropathy in order to investigate oral complaints and facial somatosensory findings. Case-control study; 29 patients (12 women, mean age 57.86 yo) with Diabetes Mellitus type 2 and 31 age-gender-matched controls were evaluated with a standardized protocol for general characteristics, orofacial pain, research diagnostic criteria for temporomandibular disorders, visual analogue scale and McGill Pain questionnaire, and a systematic protocol of quantitative sensory testing for bilateral facial sensitivity at the areas innervated by the trigeminal branches, which included the thermal detection by ThermoSensi 2, tactile evaluation with vonFrey filaments, and superficial pain thresholds with a superficial algometer (Micromar). Statistical analysis was performed with Wilcoxon, chi-square, confidence intervals and Spearman (ppain was reported by 55.2% of patients, and the most common descriptor was fatigue (50%); 17.2% had burning mouth. Myofascial temporomandibular disorders were diagnosed in 9 (31%) patients. The study group showed higher sensory thresholds of pain at the right maxillary branch (p=0.017) but sensorial differences were not associated with pain (p=0.608). Glycemia and HbA(1c) were positively correlated with the quantitative sensory testing results of pain (ppain thresholds were correlated with higher glycemia and glycated hemoglobin (p=0.027 and p=0.026). There was a high prevalence of orofacial pain and burning mouth was the most common complaint. The association of loss of pain sensation and higher glycemia and glycated hemoglobin can be of clinical use for the follow-up of DM complications. 2010 Elsevier Ltd. All rights reserved.

  3. Peripheral neuropathy

    Science.gov (United States)

    ... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  4. Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Ayumu Matsuoka

    Full Text Available Bevacizumab (BEV, a humanized anti-vascular endothelial growth factor (VEGF monoclonal antibody, enhances the antitumor effectiveness of paclitaxel (PTX-based chemotherapy in many metastatic cancers. A recent study in mice showed that VEGF receptor inhibitors can interfere with the neuroprotective effects of endogenous VEGF, potentially triggering the exacerbation of PTX-induced neuropathy. In clinical trials, exacerbation of neuropathy in patients who received PTX combined with BEV (PTX+BEV has generally been explained by increased exposure to PTX owing to the extended duration of chemotherapy. We investigated whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy.Female patients with breast cancer who had received weekly PTX or PTX+BEV from September 2011 through May 2016 were studied retrospectively. PTX-induced neuropathy was evaluated at the same time points (at the 6th and 12th courses of chemotherapy in both cohorts. A multivariate Cox proportional-hazards model was used to assess the independent effect of BEV on the time to the onset of neuropathy.A total of 107 patients (median age, 55 years; range, 32-83 were studied. Sixty-one patients received PTX as adjuvant chemotherapy, 23 received PTX for metastatic disease, and 23 received PTX+BEV for metastatic disease. Peripheral sensory neuropathy was worse in patients who received PTX+BEV than in those who received PTX alone: at the 6th course, Grade 0/1/2/3 = 4/13/4/0 vs. 25/42/6/0 (P = 0.095; at the 12th course, 2/3/11/3 vs. 7/30/23/2 (P = 0.016. At the 12th course, the incidence of Grade 2 or higher neuropathy was significantly higher in patients treated with PTX+BEV than in those treated with PTX alone (74% vs. 40%; P = 0.017. In multivariate analysis, BEV was significantly associated with an increased risk of neuropathy (HR 2.32, 95% CI 1.21-4.44, P = 0.012.The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast

  5. Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models

    Directory of Open Access Journals (Sweden)

    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.

  6. Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.

    Directory of Open Access Journals (Sweden)

    Valentina A Carozzi

    Full Text Available Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations

  7. The Effect of Preintervention Preparation on Pain and Anxiety Related to Peripheral Cannulation Procedures in Children.

    Science.gov (United States)

    Tunç-Tuna, Pinar; Açikgoz, Ayfer

    2015-12-01

    This study was performed to determine the effect of several preintervention preparation practices on pain and anxiety related to the peripheral cannulation procedure in children ages 9-12 years. The study included 60 Turkish children (28 female, 32 male, randomly selected by lot), 30 of whom were included in the intervention group and 30 of whom were included in the control group. The children's demographic data were collected by a data collection form prepared by the researcher. The children in the intervention group read the training manual before peripheral cannulation, and the procedure was demonstrated on a teddy bear. Their level of pain was assessed using the Wong-Baker Faces Rating Scale, and their level of anxiety was determined by the Spielberger State-Trait Anxiety Inventory for Children, before and during the procedure in both groups. Results showed that while anxiety and pain scores increased during the actual procedure compared to the preparatory procedure in the control group (anxiety t = -4.957, pain Z(a) = -4.048), anxiety and pain scores decreased during the actual procedure in the intervention group compared to the preparatory procedure (anxiety t = 7.896, pain t = 6.196). When the pain and anxiety scores were examined, it was found that both anxiety and pain scores in the intervention group were significantly lower than in the control group. In conclusion, children in this study experienced pain and situational anxiety during peripheral cannulation, and this pain can be reduced by preparing the child in advance of the procedure. It is suggested that children should be informed about and able to practice the procedure on a toy or model before peripheral cannulation. Preparation of the children to painful procedures in accordance with their cognitive development can reduce anxiety and pain. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  8. Mechanisms-based classifications of musculoskeletal pain: part 2 of 3: symptoms and signs of peripheral neuropathic pain in patients with low back (± leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-08-01

    As a mechanisms-based classification of pain \\'peripheral neuropathic pain\\' (PNP) refers to pain arising from a primary lesion or dysfunction in the peripheral nervous system. Symptoms and signs associated with an assumed dominance of PNP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of PNP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients\\' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of two symptoms and one sign predictive of PNP, including: \\'Pain referred in a dermatomal or cutaneous distribution\\

  9. Paclitaxel-induced apoptosis is BAK-dependent, but BAX and BIM-independent in breast tumor.

    Directory of Open Access Journals (Sweden)

    Anna V Miller

    Full Text Available Paclitaxel (Taxol-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim(-/- MEFs (mouse embryonic fibroblasts, the bim(-/- mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak (-/- MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel sensitivity was not affected in bax(-/- MEFs or in human breast cancer cells in which BAX was down-regulated, suggesting that paclitaxel-induced apoptosis is BAK-dependent, but BAX-independent. In human breast cancer cells, paclitaxel treatment resulted in MCL-1 degradation which was prevented by a proteasome inhibitor, MG132. A Cdk inhibitor, roscovitine, blocked paclitaxel-induced MCL-1 degradation and apoptosis, suggesting that Cdk activation at mitotic arrest could induce subsequent MCL-1 degradation in a proteasome-dependent manner. BAK was associated with MCL-1 in untreated cells and became activated in concert with loss of MCL-1 expression and its release from the complex. Our data suggest that BAK is the mediator of paclitaxel-induced apoptosis and could be an alternative target for overcoming paclitaxel resistance.

  10. 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...

  11. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

  12. The role of peripheral afferents in persistent inguinal postherniorrhaphy pain

    DEFF Research Database (Denmark)

    Wijayasinghe, N; Ringsted, T K; Bischoff, J M

    2016-01-01

    ) in the medial aspect of the inguinal region that triggers pain upon minimal pressure. As TPs may play a role in the pathophysiology of PIPP, the aim of this trial was to investigate the analgesic effects of local anaesthetic TP-blockade. METHODS: A randomized, double-blind, placebo-controlled, crossover trial......-algometry) and quantitative sensory testing (pressure pain thresholds, thermal detection/pain thresholds, supra-threshold heat perception), before and after the TP-blockade. RESULTS: The median (95% CI) reduction in pain was 63% (44.1 to 73.6%) after bupivacaine compared with 36% (11.6 to 49.7%; P=0.003) after placebo....... Significant increases in cool detection (P=0.01) and pressure pain thresholds (P=0.009) with decreases in supra-threshold heat pain perception (P=0.003) were seen after bupivacaine only. In four out of six volunteers, increased thermal and evoked-pain thresholds after bupivacaine compared with placebo...

  13. Peripheral analgesic effects of ketamine in acute inflammatory pain

    DEFF Research Database (Denmark)

    Pedersen, J L; Galle, T S; Kehlet, H

    1998-01-01

    BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers...... on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo...... hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P ketamine treatment compared with placebo immediately after injection (P

  14. Peripheral Mechanisms of Dental Pain: The Role of Substance P

    Directory of Open Access Journals (Sweden)

    Paola Sacerdote

    2012-01-01

    Full Text Available Current evidence supports the central role of neuropeptides in the molecular mechanisms underlying dental pain. In particular, substance P, a neuropeptide produced in neuron cell bodies localised in dorsal root and trigeminal ganglia, contributes to the transmission and maintenance of noxious stimuli and inflammatory processes. The major role of substance P in the onset of dental pain and inflammation is increasingly being recognised. Well-grounded experimental and clinical observations have documented an increase in substance P concentration in patients affected by caries, pulpitis, or granulomas and in those undergoing standard orthodontic or orthodontic/dental care procedures. This paper focuses on the role of substance P in the induction and maintenance of inflammation and dental pain, in order to define future lines of research for the evaluation of therapeutic strategies aimed at modulating the complex effects of this mediator in oral tissues.

  15. Concurrent Peripheral Pathologies and Complex Regional Pain Syndrome Type 1 as Contributors to Acute Post-Stroke Shoulder Pain: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyed Majid Akhavan Hejazi

    2012-04-01

    Full Text Available Post-stroke shoulder pain is associated with either a peripheral or central pathology. However, most of the time, it is challenging to establish a cause-and-effect relationship between the suggested pathology and shoulder pain reported. We report a 66 year-old man who developed a right hemiplegic shoulder pain two months post stroke with initial investigations suggestive of peripheral pathologies. Pharmacological and non-pharmacological treatment did not improve his shoulder pain. Later he developed complex regional pain syndrome (CRPS of the right hand and the initial shoulder pain subsequently relieved following resolution of the CRPS.

  16. Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

    Directory of Open Access Journals (Sweden)

    Coderre Terence J

    2009-09-01

    Full Text Available Abstract Background During the chronic stage of Complex Regional Pain Syndrome (CRPS, impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS. Discussion The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin. Summary The origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patient's report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients.

  17. Duloxetine for the treatment of painful diabetic peripheral neuropathy in Venezuela: economic evaluation.

    Science.gov (United States)

    Carlos, Fernando; Espejel, Luis; Novick, Diego; López, Rubén; Flores, Daniel

    2015-09-25

    Painful diabetic peripheral neuropathy affects 40-50% of patients with diabetic neuropathy, leading to impaired quality of life and substantial costs. Duloxetine and pregabalin have evidence-based support, and are formally approved for controlling painful diabetic peripheral neuropathy. We used a 12-week decision model for examining painful diabetic peripheral neuropathy first-line therapy with daily doses of duloxetine 60mg or pregabalin 300mg, under the perspective of the Instituto Venezolano de los Seguros Sociales. We gathered model parameters from published literature and expert´s opinion, focusing on the magnitude of pain relief, the presence of adverse events, the possibility of withdrawal owing to intolerable adverse events or due to lack of efficacy, and the quality-adjusted life years expected in each strategy. We analyzed direct medical costs (which are expressed in Bolívares Fuertes, BsF) comprising drug acquisition besides additional care devoted to treatment of adverse events and poor pain relief. We conducted both deterministic and probabilistic sensitivity analyses. Total expected costs per 1000 patients were BsF 1 046 146 (26%) lower with duloxetine than with pregabalin. Most of these savings (91%) corresponds to the difference in the acquisition’s cost of each medication. duloxetine also provided 23 more patients achieving good pain relief and a gain of about two quality-adjusted life years per 1000 treated. Model was robust to plausible changes in main parameters. Duloxetine remained the preferred option in 93.9% of the second-order Monte Carlo simulations. This study suggests duloxetine dominates (i.e., is more effective and lead to gains in quality-adjusted life years), remaining less costly than pregabalin for treatment of painful diabetic peripheral neuropathy.

  18. Technical Note: Treatment of Sacroiliac Joint Pain with Peripheral Nerve Stimulation.

    Science.gov (United States)

    Guentchev, Marin; Preuss, Christian; Rink, Rainer; Peter, Levente; Wocker, Ernst-Ludwig; Tuettenberg, Jochen

    2015-07-01

    Sacroiliac joint (SIJ) pain affects older adults with a prevalence of up to 20% among patients with chronic low back pain. While pain medication, joint blocks and denervation procedures achieve pain relief in most patients, some cases fail to improve. Our goal was to determine the effectiveness of SIJ peripheral nerve stimulation in patients with severe conservative therapy-refractory SIJ pain. Here we present 12 patients with severe conservative therapy-refractory pain receiving an SIJ peripheral nerve stimulation. Patient satisfaction, pain, and quality of life were evaluated by means of the International Patient Satisfaction Index (IPSI), visual analog scale (VAS), and Oswestry Disability Index 2.0 (ODI) using standard questionnaires. For stimulation we placed an eight-pole peripheral nerve electrode parallel to the SIJ. Two weeks postoperatively, our patients reported an average ODI reduction from 57% to 32% and VAS from 9 to 2.1. IPSI was 1.1. After six months, the therapy was rated as effective in seven out of eight patients reporting at that period. The average ODI was low at 34% (p = 0.0006), while the VAS index rose to 3.8 (p < 0.0001) and IPSI to 1.9. Twelve months after stimulation, six out of seven patients considered their treatment a success with an average ODI of 21% (p < 0.0005), VAS 1.7 (p < 0.0001), and IPSI 1.3. We conclude that SIJ stimulation is a promising therapeutic strategy in the treatment of intractable SIJ pain. Further studies are required to determine the precise target group and long-term effect of this novel treatment method. © 2014 International Neuromodulation Society.

  19. Painful Diabetic Peripheral Neuropathy: Consensus Recommendations on Diagnosis, Assessment and Management

    DEFF Research Database (Denmark)

    Tesfaye, S; Vileikyte, L; Rayman, G

    2011-01-01

    use of opiates such as the synthetic opioid tramadol, morphine and oxycodone controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated......Painful Diabetic peripheral neuropathy (painful DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors are proven to contribute to the aetiology...... of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been proven to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements...

  20. Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

    Directory of Open Access Journals (Sweden)

    Elaine G Boland

    Full Text Available Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN with those from healthy volunteers (HV. Twenty-four participants (n = 12 MM-CIPN, n = 12 HV underwent Blood Oxygen Level-Dependent (BOLD fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected. Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected. Significant positive correlation existed between the total neuropathy score (reduced version and activation in the frontal operculum (close to insular cortex during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87. Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

  1. Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

    International Nuclear Information System (INIS)

    Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh

    2017-01-01

    Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

  2. Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh, E-mail: ashutosh.niperhyd@gov.in

    2017-05-01

    Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

  3. The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: a pilot study

    Science.gov (United States)

    Bhatt, Ravi R; Martin, Sarah R; Evans, Subhadra; Lung, Kirsten; Coates, Thomas D; Zeltzer, Lonnie K; Tsao, Jennie C

    2017-01-01

    Background Vaso-occlusive pain crises (VOCs) are the “hallmark” of sickle-cell disease (SCD) and can lead to sympathetic nervous system dysfunction. Increased sympathetic nervous system activation during VOCs and/or pain can result in vasoconstriction, which may increase the risk for subsequent VOCs and pain. Hypnosis is a neuromodulatory intervention that may attenuate vascular and pain responsiveness. Due to the lack of laboratory-controlled pain studies in patients with SCD and healthy controls, the specific effects of hypnosis on acute pain-associated vascular responses are unknown. The current study assessed the effects of hypnosis on peripheral blood flow, pain threshold, tolerance, and intensity in adults with and without SCD. Subjects and methods Fourteen patients with SCD and 14 healthy controls were included. Participants underwent three laboratory pain tasks before and during a 30-minute hypnosis session. Peripheral blood flow, pain threshold, tolerance, and intensity before and during hypnosis were examined. Results A single 30-minute hypnosis session decreased pain intensity by a moderate amount in patients with SCD. Pain threshold and tolerance increased following hypnosis in the control group, but not in patients with SCD. Patients with SCD exhibited lower baseline peripheral blood flow and a greater increase in blood flow following hypnosis than controls. Conclusion Given that peripheral vasoconstriction plays a role in the development of VOC, current findings provide support for further laboratory and clinical investigations of the effects of cognitive–behavioral neuromodulatory interventions on pain responses and peripheral vascular flow in patients with SCD. Current results suggest that hypnosis may increase peripheral vasodilation during both the anticipation and experience of pain in patients with SCD. These findings indicate a need for further examination of the effects of hypnosis on pain and vascular responses utilizing a randomized

  4. Effect of kamikihito (TJ-137) on paclitaxel-induced olfactory neuropathy in vivo

    International Nuclear Information System (INIS)

    Yamamoto, Junpei

    2012-01-01

    A Kampo product, kamikihito (product name code: TJ-137), has ingredients that promote nerve growth. Paclitaxel, a cancer chemotherapeutic agent, is toxic to olfactory nerve cells in vivo. We found that TJ-137 is effective in reducing paclitaxel induced olfactory neuropathy in vivo. Female 7-week-old Bulb/c mice were fed food containing TJ-137, or control food, for 14 days before and after intravenous paclitaxel administration. 201 Tl uptake in nasal turbinates of TJ-137 treated mice (n=8) and control mice (n=9) was assessed by gamma spectrometry 6 hrs after nasal administration of 201 Tl. The epithelial changes in the nasal turbinates of mice were assessed by H and E and immunohistochemical staining for the olfactory marker protein (OMP). The accumulation of the neuronal tracer (Dextran tetramethylrhodamine) in the olfactory bulb was assessed in frozen sections of mice 48 hrs after nasal administration of the tracer. The epithelium of nasal turbinates of TJ-137 treated mice was less injured than that of the control mice after paclitaxel administration. The nasal epithelium was significantly thicker in TJ-137 treated mice compared to control mice (P=0.019). The accumulation of the neuronal tracer in the olfactory bulb was higher in the TJ-137 treated mice compared to controls. 201 Tl uptake per weight in nasal turbinate of TJ-137 treated mice was significantly higher than that of control mice (P=0.008). Pre-medication with TJ-137 (kamikihito) was effective in increasing olfactory nerve viability after paclitaxel administration in vivo. (author)

  5. Profound and persistent painful paclitaxel peripheral neuropathy in a premenopausal patient.

    LENUS (Irish Health Repository)

    Quintyne, K I

    2011-01-01

    The authors herein report the case of a 35-year-old woman undergoing adjuvant therapy for node positive breast cancer, who presented with short and rapidly progressive history of bilateral lower limb symptoms of peripheral neuropathy following therapy with paclitaxel. MRI of her neural axis revealed no leptomeningeal enhancement or focal metastatic lesions. Neurophysiological tests favoured toxic sensory axonal polyneuropathy. She remains symptomatic following discontinuation of therapy 20 months ago, and is under review with pain management.

  6. 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.

  7. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Arjun eMuralidharan

    2016-05-01

    Full Text Available Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤450g of gravel on any two days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund’s complete adjuvant (FCA or saline, or underwent unilateral chronic constriction injury (CCI of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA- and CCI-rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

  8. 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.

  9. Long-Term Reduction of Sacroiliac Joint Pain With Peripheral Nerve Stimulation.

    Science.gov (United States)

    Guentchev, Marin; Preuss, Christian; Rink, Rainer; Peter, Levente; Sailer, Martin H M; Tuettenberg, Jochen

    2017-10-01

    We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment. To investigate the long-term (up to 4 years) response rate of this novel treatment. Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient. Quality of life, pain, and patient satisfaction were assessed using the Oswestry Disability Index 2.0, Visual Analog Scale (VAS), and International Patient Satisfaction Index. Patients reported a pain reduction from 8.8 to 1.6 (VAS) at 1 year ( P < .001), and 13 of 14 patients (92.9%) rated the therapy as effective (International Patient Satisfaction Index score ≤ 2). At 2 years, average pain score was 1.9 ( P < .001), and 9 of 10 patients (90.0%) considered the treatment a success. At 3 years, 8 of 9 patients (88.9%) were satisfied with the treatment results, reporting an average VAS of 2.0 ( P < .005). At 4 years, 2 of 3 patients were satisfied with the treatment results. We have shown for the first time that PNS is a successful long-term therapy for SIJ pain. Copyright © 2017 by the Congress of Neurological Surgeons

  10. 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

  11. Management of pain secondary to temporomandibular joint syndrome with peripheral nerve stimulation.

    Science.gov (United States)

    Rodriguez-Lopez, Manuel J; Fernandez-Baena, Mariano; Aldaya-Valverde, Carlos

    2015-01-01

    Temporomandibular joint syndrome, or Costen syndrome, is a clinically diagnosed disorder whose most common symptoms include joint pain and clicking, difficulty opening the mouth, and temporomandibular joint discomfort. The temporomandibular joint (TMJ) is supplied by the auriculotemporal nerve, a collateral branch of the mandibular nerve (the V3 branch of the trigeminal nerve). The aim of this study is to assess the effectiveness and safety of permanent peripheral nerve stimulation to relieve TMJ pain. This case series is a prospective study. Pain Unit of a regional universitary hospital. The study included 6 female patients with temporomandibular pain lasting from 2 to 8 years that did not respond to intraarticular local anesthetic and corticoid injections. After a positive diagnostic block test, the patients were implanted with quadripolar or octapolar leads in the affected preauricular region for a 2-week stimulation test phase, after which the leads were connected to a permanent implanted pulse generator. Results of the visual analog scale, SF-12 Health Survey, Brief Pain Inventory, and drug intake were recorded at baseline and at 4, 12, and 24 weeks after the permanent implant. Five out of 6 patients experienced pain relief exceeding 80% (average 72%) and received a permanent implant. The SF-12 Health Survey results were very positive for all specific questions, especially items concerning the physical component. Patients reported returning to normal physical activity and rest at night. Four patients discontinued their analgesic medication and 1 patient reduced their gabapentin dose by 50%. Sample size; impossibility of placebo control. Patients affected with TMJ syndrome who do not respond to conservative treatments may find a solution in peripheral nerve stimulation, a simple technique with a relatively low level of complications.

  12. 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.

  13. Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective multicenter study.

    Science.gov (United States)

    Kloimstein, Herwig; Likar, Rudolf; Kern, Michael; Neuhold, Josef; Cada, Miroslav; Loinig, Nadja; Ilias, Wilfried; Freundl, Brigitta; Binder, Heinrich; Wolf, Andreas; Dorn, Christian; Mozes-Balla, Eva Maria; Stein, Rolf; Lappe, Ivo; Sator-Katzenschlager, Sabine

    2014-02-01

    The goal of this study was to evaluate the long-term efficacy and safety of peripheral nerve field stimulation (PNFS) for chronic low back pain (cLBP). In this prospective, multicenter observational study, 118 patients were admitted to 11 centers throughout Austria and Switzerland. After a screening visit, all patients underwent a trial stimulation period of at least seven days before implantation of the permanent system. Leads were placed in the subcutaneous tissues of the lower back directly in the region of greatest pain. One hundred five patients were implanted with a permanent stimulating system. Patients' evaluation of pain and functional levels were completed before implantation and one, three, and six months after implantation. Adverse events, medication usage, and coverage of the painful area and predictive value of transcutaneous electrical nerve stimulation (TENS) were monitored. All pain and quality-of-life measures showed statistically significant improvement during the treatment period. These included the average pain visual analog scale, the Oswestry Disability Questionnaire, the Becks Depression Inventory, and the Short Form-12 item Health survey. Additionally, medication usage with opioids, nonsteroidal anti-inflammatory drugs, and anti-convulsants showed a highly significant reduction. Complications requiring surgical intervention were reported in 9.6% of the patients. The degree of coverage of painful areas seems to be an important criterion for efficacy of PNFS, whereas TENS is presumably no predictor. This prospective, multicenter study confirms that PNFS is an effective therapy for the management of cLBP. Significant improvements in many aspects of the pain condition were measured, and complications were minimal. © 2013 International Neuromodulation Society.

  14. The effects of electroacupuncture on analgesia and peripheral sensory thresholds in patients with burn scar pain.

    Science.gov (United States)

    Cuignet, Olivier; Pirlot, A; Ortiz, S; Rose, T

    2015-09-01

    The aim of this study is to observe if the effects of electro-acupuncture (EA) on analgesia and peripheral sensory thresholds are transposable from the model of heat pain in volunteers to the clinical setting of burn scar pain. After severe burns, pathological burn scars (PPBS) may occur with excruciating pain that respond poorly to treatment and prevent patients from wearing their pressure garments, thereby leading to unesthetic and function-limiting scars. EA might be of greater benefit in terms of analgesia and functional recovery, should it interrupt this vicious circle by counteracting the peripheral hyperalgesia characterizing PPBS. Therefore we enrolled 32 patients (22 males/10 females) aged of 46±11 years with clinical signs of PPBS and of neuropathic pain despite treatment. The study protocol consisted in 3 weekly 30-min sessions of standardized EA with extra individual needles in accordance to Traditional Chinese Medicine, in addition of previous treatments. We assessed VAS for pain and quantitative sensory testing (QST) twice: one week before and one after protocol. QST measured electrical thresholds for non-nociceptive A-beta fibers, nociceptive A-delta and C fibers in 2 dermatomes, respectively from the PPBS and from the contralateral pain-free areas. Based on heat pain studies, EA consisted in sessions at the extremity points of the main meridian flowing through PPBS (0.300s, 5Hz, sub noxious intensity, 15min) and at the bilateral paravertebral points corresponding to the same metameric level, 15min. VAS reduction of 3 points or below 3 on a 10 points scale was considered clinically relevant. Paired t-test compared thresholds (mean [SD]) and Wilcoxon test compared VAS (median [IQR]) pre and after treatment, significant ppatients - even those from the subgroup of non-responders to pain - that is worth to be mentioned and requires further studies to be confirmed. This observational study is the first that confirms the effects of acupuncture on

  15. Selective Fiber Degeneration in the Peripheral Nerve of a Patient With Severe Complex Regional Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Adrien Yvon

    2018-04-01

    Full Text Available Aims: Complex regional pain syndrome (CRPS is characterized by chronic debilitating pain disproportional to the inciting event and accompanied by motor, sensory, and autonomic disturbances. The pathophysiology of CRPS remains elusive. An exceptional case of severe CRPS leading to forearm amputation provided the opportunity to examine nerve histopathological features of the peripheral nerves.Methods: A 35-year-old female developed CRPS secondary to low voltage electrical injury. The CRPS was refractory to medical therapy and led to functional loss of the forelimb, repeated cutaneous wound infections leading to hospitalization. Specifically, the patient had exhausted a targeted conservative pain management programme prior to forearm amputation. Radial, median, and ulnar nerve specimens were obtained from the amputated limb and analyzed by light and transmission electron microscopy (TEM.Results: All samples showed features of selective myelinated nerve fiber degeneration (47–58% of fibers on electron microscopy. Degenerating myelinated fibers were significantly larger than healthy fibers (p < 0.05, and corresponded to the larger Aα fibers (motor/proprioception whilst smaller Aδ (pain/temperature fibers were spared. Groups of small unmyelinated C fibers (Remak bundles also showed evidence of degeneration in all samples.Conclusions: We are the first to show large fiber degeneration in CRPS using TEM. Degeneration of Aα fibers may lead to an imbalance in nerve signaling, inappropriately triggering the smaller healthy Aδ fibers, which transmit pain and temperature. These findings suggest peripheral nerve degeneration may play a key role in CRPS. Improved knowledge of pathogenesis will help develop more targeted treatments.

  16. Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states

    Directory of Open Access Journals (Sweden)

    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.

  17. Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice

    Directory of Open Access Journals (Sweden)

    Dorsey Susan G

    2011-04-01

    Full Text Available Abstract Background A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH wide dynamic range neurons in oxaliplatin-treated mice Results We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.

  18. Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways.

    Science.gov (United States)

    Zheng, Gen; Hong, Shuangsong; Hayes, John M; Wiley, John W

    2015-11-01

    Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control DRGs treated with corticosterone in vitro. The reciprocal changes of CB1, TRPV1 and sodium channels were cell-specific and observed in the sub-population of nociceptive neurons. Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Role of cytochrome P450 2C8*3 (CYP2C8*3) in paclitaxel metabolism and paclitaxel-induced neurotoxicity

    DEFF Research Database (Denmark)

    Lee, Mi-Young; Apellániz-Ruiz, María; Johansson, Inger

    2015-01-01

    AIM: The CYP2C8*3 allele has been suggested as a risk factor for paclitaxel-induced neuropathy but the data hitherto published are conflicting. MATERIALS & METHODS: In total 435 patients were investigated with respect to maximum neuropathy grade and accumulated paclitaxel dose. The enzymatic prop...

  20. Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury

    Directory of Open Access Journals (Sweden)

    Nan Gu

    2016-07-01

    Full Text Available Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT by using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.

  1. Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms

    Science.gov (United States)

    Wang, Ying; Lei, Jianxun; Gupta, Mihir; Peng, Fei; Lam, Sarah; Jha, Ritu; Raduenz, Ellis; Beitz, Al J.; Gupta, Kalpna

    2016-01-01

    Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund’s adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints. PMID:27687125

  2. Electromagnetic Field Devices and Their Effects on Nociception and Peripheral Inflammatory Pain Mechanisms.

    Science.gov (United States)

    Ross, Christina L; Teli, Thaleia; Harrison, Benjamin S

    2016-03-01

    -dependent interaction between the mechanical interventions of EMF and cell signaling along the peripheral inflammatory pain pathway.

  3. Peripheral and central components of habituation of heat pain perception and evoked potentials in humans.

    Science.gov (United States)

    Greffrath, Wolfgang; Baumgärtner, Ulf; Treede, Rolf-Detlef

    2007-12-05

    For the neurophysiological examination of nociceptive pathways, contact-heat evoked potentials (contact-heat EPs) are elicited by repetitive brief noxious heat stimuli. Suppression of heat responses in primary nociceptive neurons during repetitive stimulation has been shown in animal models in vivo and in vitro. We now investigated whether heat pain and contact-heat EPs in humans display equivalent signs of habituation. Heat pain and EPs were elicited in 16 volunteers with a contact thermode (30 degrees Cs(-1)). Heat pulses at three intensities (pain threshold, moderate noxious and maximum available) were applied to the right forearm either by moving the thermode after each pulse to variable locations or when fixed to one location (inter-stimulus intervals 8-10s). Contact-heat EPs consisted of an early negativity in temporal leads (N1), followed by a biphasic response at the vertex (N2-P2). Pain ratings and contact-heat EPs (N1 and N2-P2 components) displayed significant temperature dependence. N2-P2 correlated positively with ratings. With stimulation at variable locations, both measures slowly decreased with time constants tau of 2 min (ratings) and 12 min (EPs). With stimulation at a fixed location, habituation was much faster for both, ratings (tau=10s) and EPs (tau=33 s). As a consequence, both measures were significantly reduced (pheat pain perception and contact-heat EPs display signs of rapid habituation when stimulation is restricted to a fixed location and thus, reflect fatigue of peripheral nociceptive neurons. Habituation within the central nervous system is slower and less pronounced.

  4. Liposomal bupivacaine peripheral nerve block for the management of postoperative pain.

    Science.gov (United States)

    Hamilton, Thomas W; Athanassoglou, Vassilis; Trivella, Marialena; Strickland, Louise H; Mellon, Stephen; Murray, David; Pandit, Hemant G

    2016-08-25

    Postoperative pain remains a significant issue with poor perioperative pain management associated with an increased risk of morbidity and mortality. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained release. To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration peripheral nerve block for the management of postoperative pain. We identified randomised trials of liposomal bupivacaine peripheral nerve block for the management of postoperative pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), Ovid MEDLINE (1946 to January Week 1 2016), Ovid MEDLINE In-Process (14 January 2016), EMBASE (1974 to 13 January 2016), ISI Web of Science (1945 to 14 January 2016), and reference lists of retrieved articles. We sought unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials. The date of the most recent search was 15 January 2016. Randomised, double-blind, placebo- or active-controlled clinical trials of a single dose of liposomal bupivacaine administered as a peripheral nerve block in adults aged 18 years or over undergoing elective surgery at any surgical site. We included trials if they had at least two comparison groups for liposomal bupivacaine peripheral nerve block compared with placebo or other types of analgesia. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We performed analyses using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5. We planned to perform a meta-analysis, however there were insufficient data to ensure a clinically meaningful answer; as such we have produced a 'Summary of findings' table in a narrative format, and where possible we assessed the

  5. Pain reduction peripheral arteriographies of the upper and lower extriemities in a double blind test

    International Nuclear Information System (INIS)

    Schmidt, K.R.; Pfeifer, K.J.; Huber, R.; Welter, H.

    1980-01-01

    36 aortofemoral and 18 brachial angiographies effected under standardized conditions in a double blind test in approximately two equal parts with Lidocain/Ioglicinate and Metrizamide, respectively, were evaluated with regard to vascular pain and sensation of heat during the examination. With the femoralis angiograms reduction of vascular pain was on the average somewhat greater, although this could not be established statistically when using Metrizamide. In the case of the angiogram of the arm, pain was on the average equally low in both cases. Of the 14 patients who had received injections of both contrast media in varying succession at intervals of 20 minutes, 6 patients considered the Metrizamide injection to be more agreeable, whereas 2 preferred the Lidocain/Ioglicinate injection and 6 patients did not notice any significant difference. The average sensation of heat during contrast medium visualisation of the legs and arms was equal with both substances. Lidocain/Ioglicinate and Metrizamide are approximately equally well suited for peripheral angiography of arms and legs, rendering narcosis and strapping down of the extremities unneccessary in normal cases. (orig.) [de

  6. The Discriminative validity of "nociceptive," "peripheral neuropathic," and "central sensitization" as mechanisms-based classifications of musculoskeletal pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-02-01

    OBJECTIVES: Empirical evidence of discriminative validity is required to justify the use of mechanisms-based classifications of musculoskeletal pain in clinical practice. The purpose of this study was to evaluate the discriminative validity of mechanisms-based classifications of pain by identifying discriminatory clusters of clinical criteria predictive of "nociceptive," "peripheral neuropathic," and "central sensitization" pain in patients with low back (+\\/- leg) pain disorders. METHODS: This study was a cross-sectional, between-patients design using the extreme-groups method. Four hundred sixty-four patients with low back (+\\/- leg) pain were assessed using a standardized assessment protocol. After each assessment, patients\\' pain was assigned a mechanisms-based classification. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various clinical criteria. RESULTS: Multivariate analyses using binary logistic regression with Bayesian model averaging identified a discriminative cluster of 7, 3, and 4 symptoms and signs predictive of a dominance of "nociceptive," "peripheral neuropathic," and "central sensitization" pain, respectively. Each cluster was found to have high levels of classification accuracy (sensitivity, specificity, positive\\/negative predictive values, positive\\/negative likelihood ratios). DISCUSSION: By identifying a discriminatory cluster of symptoms and signs predictive of "nociceptive," "peripheral neuropathic," and "central" pain, this study provides some preliminary discriminative validity evidence for mechanisms-based classifications of musculoskeletal pain. Classification system validation requires the accumulation of validity evidence before their use in clinical practice can be recommended. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  7. Text Messaging to Improve Disease Management in Patients With Painful Diabetic Peripheral Neuropathy.

    Science.gov (United States)

    Bauer, Victoria; Goodman, Nancy; Lapin, Brittany; Cooley, Camille; Wang, Ed; Craig, Terri L; Glosner, Scott E; Juhn, Mark S; Cappelleri, Joseph C; Sadosky, Alesia B; Masi, Christopher

    2018-06-01

    Purpose The purpose of the study was to determine the impact of educational text messages on diabetes self-management activities and outcomes in patients with painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN identified from a large integrated health system who agreed to participate were randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self-management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes health beliefs, and glycated hemoglobin (A1C). Changes from baseline were evaluated at 6 months and compared between groups. Results Demographic characteristics were balanced between groups (N = 62; 53% female, mean age = 63 years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no difference between groups. UC+TxtM but not UC was associated with significant improvements from baseline on all SDSCA subscales. On diabetes health beliefs, UC+TxtM patients reported significantly increased benefits and reduced barriers and susceptibility relative to UC at 6 months. A1C declined in both groups, but neither change was significant relative to baseline. Conclusions Patients with pDPN who receive twice-daily text messages regarding diabetes management reported reduced pain relative to baseline, although this change was not significant compared with usual care. In addition, text messaging was associated with increased self-management activities and improved diabetes health beliefs and total self-care. These results warrant further investigation.

  8. Pain-relieving effectiveness, quality of life and tolerability of repeated capsaicin 8% patch treatment of peripheral neuropathic pain in Scandinavian clinical practice

    DEFF Research Database (Denmark)

    Hansson, P; Jensen, Troels Staehelin; Kvarstein, G

    2018-01-01

    CONTEXT: Clinical trials have demonstrated the efficacy and safety of the capsaicin 8% patch in patients with peripheral neuropathic pain (PNP); however, few studies have assessed this treatment in a clinical practice. OBJECTIVE: To determine whether treatment and re-treatment with the capsaicin ...

  9. 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...

  10. Peripheral Neuropathic Facial/Trigeminal Pain and RANTES/CCL5 in Jawbone Cavitation

    Directory of Open Access Journals (Sweden)

    Johann Lechner

    2015-01-01

    Full Text Available Introduction. In this study, we elucidate the possible causative role of chronic subclinical inflammation in jawbone of patients with atypical facial pain (AFP and trigeminal neuralgia (TRN in the local overexpression of the chemokine regulated on activation and normal T-cell expressed and secreted (RANTES/C-C motif ligand 5 CCL5. Neurons contain opioid receptors that transmit antipain reactions in the peripheral and central nervous system. Proinflammatory chemokines like RANTES/CCL5 desensitize μ-opioid receptors in the periphery sensory neurons and it has been suggested that RANTES modifies the nociceptive reaction. Materials and Methods. In 15 patients with AFP/TRN, we examined fatty degenerated jawbone (FDOJ samples for the expression of seven cytokines by multiplex analysis and compared these results with healthy jawbones. Results. Each of these medullary jawbone samples exhibited RANTES as the only highly overexpressed cytokine. The FDOJ cohort with AFP/TRN showed a mean 30-fold overexpression of RANTES compared to healthy jawbones. Conclusions. To the best of our knowledge, no other research has identified RANTES overexpression in silent inflamed jawbones as a possible cause for AFP/TRN. Thus, we hypothesize that the surgical clearing of FDOJ might diminish RANTES signaling pathways in neurons and contribute to resolving chronic neurological pain in AFP/TRN patients.

  11. The validity of upper-limb neurodynamic tests for detecting peripheral neuropathic pain.

    Science.gov (United States)

    Nee, Robert J; Jull, Gwendolen A; Vicenzino, Bill; Coppieters, Michel W

    2012-05-01

    The validity of upper-limb neurodynamic tests (ULNTs) for detecting peripheral neuropathic pain (PNP) was assessed by reviewing the evidence on plausibility, the definition of a positive test, reliability, and concurrent validity. Evidence was identified by a structured search for peer-reviewed articles published in English before May 2011. The quality of concurrent validity studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool, where appropriate. Biomechanical and experimental pain data support the plausibility of ULNTs. Evidence suggests that a positive ULNT should at least partially reproduce the patient's symptoms and that structural differentiation should change these symptoms. Data indicate that this definition of a positive ULNT is reliable when used clinically. Limited evidence suggests that the median nerve test, but not the radial nerve test, helps determine whether a patient has cervical radiculopathy. The median nerve test does not help diagnose carpal tunnel syndrome. These findings should be interpreted cautiously, because diagnostic accuracy might have been distorted by the investigators' definitions of a positive ULNT. Furthermore, patients with PNP who presented with increased nerve mechanosensitivity rather than conduction loss might have been incorrectly classified by electrophysiological reference standards as not having PNP. The only evidence for concurrent validity of the ulnar nerve test was a case study on cubital tunnel syndrome. We recommend that researchers develop more comprehensive reference standards for PNP to accurately assess the concurrent validity of ULNTs and continue investigating the predictive validity of ULNTs for prognosis or treatment response.

  12. Paclitaxel-induced hypothermia and hypoperfusion increase breast cancer metastasis and angiogenesis in mice

    Science.gov (United States)

    Ami, Nozomi; Sato, Hideki; Hayakawa, Yoshihiro

    2018-01-01

    Housing temperature has been shown to influence thermoregulation and behavior of preclinical cancer models; and anti-cancer drugs typically reduce peripheral blood flow and body temperature. In the present study, the effects of paclitaxel (PTX)-induced reduction of body temperature and peripheral blood flow on metastatic 4T1 breast cancer was investigated in a mouse model and the modification of these effects by thermoneutral temperature was also assessed. A single dose of PTX decreased the body temperature and peripheral blood flow in mice housed at a standard temperature (23°C). Furthermore, although lung metastasis and angiogenesis of inoculated 4T1 cells increased in mice pretreated with PTX, mice housed at a thermoneutral temperature (30°C) could compensate their body temperature and peripheral blood flow compared with control mice, and also suppressed 4T1 angiogenesis and metastasis to lung. The present results imply that maintenance of body temperature or efficient energy supply for thermogenesis may prevent tumor relapse or metastasis after chemotherapy. PMID:29434941

  13. Tanshinone IIA Attenuates Diabetic Peripheral Neuropathic Pain in Experimental Rats via Inhibiting Inflammation

    Directory of Open Access Journals (Sweden)

    Baojian Zhang

    2018-01-01

    Full Text Available Diabetic peripheral neuropathic pain (DPNP is a common and intractable complication of diabetes. Conventional therapies are always not ideal; development of novel drugs is still needed to achieve better pain relief. Recent evidences have demonstrated that inflammation is involved in the onset and maintenance of DPNP. The anti-inflammatory property of Tanshinone IIA (TIIA makes it a promising candidate to block or alter the pain perception. This study was conducted to investigate whether TIIA could attenuate DPNP in streptozotocin- (STZ- induced rats model and its potential mechanisms. TIIA was administered to STZ-induced diabetic rats at the dose of 40 mg/kg once a day for 3 weeks. The effects of TIIA on thermal hyperalgesia and mechanical allodynia were investigated using behavioral tests. The mRNA level and expression of interleukin- (IL- 1β, interleukin- (IL- 6, tumor necrosis factor- (TNF- α, and interleukin- (IL- 10 in the fourth to sixth segments of the dorsal root ganglion (L4–6 DRG were detected by quantitative real-time PCR (qPCR and Western blot. TIIA treatment significantly attenuated mechanical allodynia and thermal hyperalgesia in diabetic rats. In addition, the expression of the proinflammatory cytokines IL-1β, IL-6, and TNF-α was inhibited, and the level of the anti-inflammatory cytokine IL-10 was increased by TIIA. This study demonstrated that TIIA has significant antiallodynic and antihyperalgesic effects in a rat model of STZ-induced DPNP, and the effect may be associated with its anti-inflammation property.

  14. Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain

    Directory of Open Access Journals (Sweden)

    Busch Melanie

    2009-12-01

    Full Text Available Abstract Background Leukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, anti-bacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC on complete Freund's adjuvant-induced inflammatory pain in rats. Results POMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin. Conclusion Although MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.

  15. Burden of Illness of Diabetic Peripheral Neuropathic Pain: A Qualitative Study.

    Science.gov (United States)

    Brod, Meryl; Pohlman, Betsy; Blum, Steven I; Ramasamy, Abhilasha; Carson, Robyn

    2015-08-01

    Diabetic peripheral neuropathy (DPN) is the result of nerve damage in the toes, feet, or hands, causing loss of feeling or pain for up to 50% of patients. The purpose of this qualitative study was to assess the burden and impact of DPN pain (DPNP) symptoms on patient's functioning and well-being. Four focus groups and 47 telephone interviews were conducted to understand the experience and impacts of DPNP from the patient's perspective. All participants were over the age of 18 years, read/spoke English, had a documented diagnosis of DPNP with symptoms for 6 months and a minimum 12-month history of diabetes mellitus, and had a daily pain rating of at least 4 on an 11-point numerical rating scale. Interview transcripts were analyzed thematically based on modified grounded theory principles. There were 70 respondents--48 (68.6%) males and 22 (31.4%) females. The mean age was 54.0 years (range 26-70), and nearly all respondents had type 2 diabetes (87%). Analysis identified four major areas of impact; DPNP patients reported difficulties with: (1) physical function, i.e. walking, exercise, energy, standing, balance, bending, and mobility; (2) daily life, i.e. productivity, recreational activities, work, enjoyment, focus, and chores; (3) social/psychological, i.e. anxiety, friends/family, irritability, depression, and fear; and (4) sleep, i.e. sleep, falling asleep, waking in the night, returning to sleep, and not feeling rested upon awakening. DPNP is a significant complication of diabetes with multiple impacts for patient functioning and well-being, which increase the burden of disease.

  16. Evaluating the efficacy of lavender aromatherapy on peripheral venous cannulation pain and anxiety: A prospective, randomized study.

    Science.gov (United States)

    Karaman, Tugba; Karaman, Serkan; Dogru, Serkan; Tapar, Hakan; Sahin, Aynur; Suren, Mustafa; Arici, Semih; Kaya, Ziya

    2016-05-01

    This study was designed to evaluate the effectiveness of lavender aromatherapy on pain, anxiety, and level of satisfaction associated with the peripheral venous cannulation (PVC) in patients undergoing surgery. One hundred and six patients undergoing surgery were randomized to receive aromatherapy with lavender essential oil (the lavender group) or a placebo (the control group) during PVC. The patients' pain, anxiety, and satisfaction scores were measured. There was no statistically significantly difference between the groups in terms of demographic data. After cannulation, the pain and anxiety scores (anxiety 2) of the patients in the lavender group were significantly lower than the control group (for p = 0.01 for pain scores; p aromatherapy had beneficial effects on PVC pain, anxiety, and satisfaction level of patients undergoing surgery. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.

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    Kouichi Isami

    Full Text Available Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2 expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages into the injured nerve and spinal cord by using bone marrow (BM chimeric mice by crossing wildtype (WT and TRPM2-knockout (TRPM2-KO mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP(+ BM cells (TRPM2(BM+/Rec+, TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+ mice was attenuated in TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. The numbers of GFP(+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP(+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2(BM+/Rec+ mice. However, the numbers of GFP(-/Iba1(+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal

  18. Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy

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    Daisuke Kawata

    2017-09-01

    Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3 or interleukin-10 (IL-10 from replication-defective herpes simplex virus (HSV-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2, and expression of the transgene was controlled by doxycycline (DOX. We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.

  19. Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy.

    Science.gov (United States)

    Kawata, Daisuke; Wu, Zetang

    2017-09-15

    Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.

  20. Prevalence and biochemical risk factors of diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese adults with type 2 diabetes mellitus.

    Science.gov (United States)

    Pai, Yen-Wei; Lin, Ching-Heng; Lee, I-Te; Chang, Ming-Hong

    To investigate the prevalence and risk factors for diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese. A cross-sectional, hospital-based observational study was conducted. We enrolled 2837 adults with type 2 diabetes mellitus. Diabetic peripheral neuropathy with or without pain were diagnosed using 2 validated screening tools, namely the Michigan Neuropathy Screening Instrument and Douleur Neuropathique 4 questionnaire. In our sample, 2233 participants had no neuropathy, 476 had diabetic peripheral neuropathy without pain, and 128 had diabetic peripheral neuropathy with neuropathic pain, representing an overall diabetic peripheral neuropathy prevalence of 21.3%, and the prevalence of neuropathic pain in diabetic peripheral neuropathy was 21.2%. Multivariate analysis revealed that older age (Pperipheral neuropathy, whereas older age (Pperipheral neuropathy with neuropathic pain. During clinical visits involving biochemical studies, the risk for diabetic peripheral neuropathy with neuropathic pain should be considered for people with older age, elevated glycated haemoglobin, low high-density lipoprotein cholesterol and overt proteinuria, with particular attention given to increased levels of albuminuria while concerning neuropathic pain. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  1. Selective peripheral nerve resection for treatment of persistent pain around the knee joint after total knee arthroplasty.

    Science.gov (United States)

    Zhong, Guangjun; Liang, Zhu; Kan, Jiang; Muheremu, Aikeremujiang

    2018-01-01

    Objective This study was performed to determine the efficacy of selective peripheral nerve resection for treatment of persistent neuropathic pain after total knee arthroplasty (TKA). Methods Patients who underwent TKA in our department from January 2013 to July 2016 and experienced persistent pain around the knee joint after TKA were retrospectively included in the current study. Sixty patients were divided into experimental and control groups according the treatment they received. The treatment effect was evaluated by the Hospital for Special Surgery (HSS) knee score and visual analog scale (VAS) pain score preoperatively and at 1, 2, 3, 6, and 12 months postoperatively. Results The HSS knee scores were higher in both groups after than before the treatment, and HSS knee scores were significantly higher in the experimental group than in the control group. The VAS pain scores were lower in both groups after than before the treatment, and VAS pain scores were significantly lower in the experimental group than in the control group. Conclusions Selective peripheral nerve resection is an effective treatment method for persistent neuropathic pain after TKA.

  2. Correlation between pain response and improvements in patient-reported outcomes and health-related quality of life in duloxetine-treated patients with diabetic peripheral neuropathic pain

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    Ogawa K

    2015-08-01

    Full Text Available Kei Ogawa,1 Shinji Fujikoshi,2 William Montgomery,3 Levent Alev1 1Medical Science, 2Statistical Science, Eli Lilly Japan K.K., Kobe, Japan; 3Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia Objective: We assessed whether quality of life (QoL improvement in duloxetine-treated patients with diabetic peripheral neuropathic pain (DPNP correlates with the extent of pain relief.Methods: Pooled data from three multicountry, double-blind, 12-week, placebo-controlled trials of duloxetine-treated (duloxetine 60 mg once daily; total number =335 patients with DPNP were analyzed. Based on improvement in 24-hour average pain scores, patients were stratified into four groups. Improvement in QoL, which was measured as the change from baseline in two patient-reported health outcome measures (Short Form [SF]-36 and five-dimension version of the EuroQol Questionnaire [EQ-5D], was evaluated and compared among the four groups. Pearson’s correlation coefficient was calculated to assess the correlation between improvement in pain scores and improvement in QoL.Results: The group with more pain improvement generally showed greater mean change from baseline in all of the SF-36 scale scores and on the EQ-5D index. Pearson’s correlation coefficients ranged from 0.114 to 0.401 for the SF-36 scale scores (P<0.05, and it was 0.271 for the EQ-5D (P<0.001.Conclusion: Improvement in pain scores was positively correlated with improvement in QoL and patient-reported outcomes in duloxetine-treated patients. Keywords: diabetic peripheral neuropathic pain, duloxetine, efficacy, function, quality of life

  3. Investigating and comparing effects of atropine and physostigmine in peripheral pain examination due to formalin injection on rats

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    Mohammad Pourahmadi

    2016-07-01

    Full Text Available There areseveral neurotransmittersat feel the pain and processing nervoussystem, and until now cholinergic system has not been well studied in this field. The purpose of this research is investigating effects of atropine and physostigmine on the response of formalin pain test. We divided 50 male wistar head rats into 5 groups , first group ( saline normal injection 5 µ , second group ( 1% formalin injection into 50 µ , third group ( physostigmine injection 0/1 mg / kg , fourth group (atropine injection 2 mg / kg , fifth group ( atropine injection 2 mg / kg and physostigmine 0/1 mg/kg , after formalin injection , the animals were placed inside mirror pain machine and it was recorded pain response at the time ranges 0-5 and 15-45 . Results investigated with spss software and ANOVA and Duncan’s test. Formalin injection causes pain response in both time ranges. Atropine injection alone had no effect on pain response. Physostigmine effect alone, with a significant reduction (p< 0/05 in the number of foot motions in both stage and duration causesof licking and biting in the 15-45 minutes stage . Atropine and physostigmine injections in fifth group cause significant reduction in the number of foot motions and duration of licking and biting in the time range of 15-45 minutes.Perhaps there is a close relationship between cholinergic system and peripheral pain that can be taken through the action of muscarinic receptors.

  4. 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.

  5. The peripheral and central mechanisms of transition of acute to chronic pain and the possible role of cyclooxygenase-2 inhibition in the prevention of pain syndrome chronization

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    O. S. Davydov

    2016-01-01

    Full Text Available Chronic pain syndromes as a cause of suffering, short-term or persistent disability, and social losses greatly worsen quality of life. The mechanisms leading to the occurrence and maintenance of chronic pain are traditionally of interest for in-depth study since each of them is potentially a target for pharmacotherapy. Peripheral and central sensitizations, as well as disinhibition make different contributions to the development of chronic pain. The fact that cyclooxygenase-2 (COX-2 inhibitors may affect at both the peripheral and central, spinal levels, by modulating such a phenomenon as central sensitization, has been recently discussed. There are theoretical prerequisites for a discussion of this action of COX-2 inhibitors; however, clinical findings supporting this hypothesis have been scarce so far. In this connection, of interest is the clinical trial published in 2016, which may suggest to a high degree of accuracy that some analgesic effect of the selective COX-2 inhibitor etoricoxib is realized through the central mechanisms of pain modulation. 

  6. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis.

    Science.gov (United States)

    Barr, Andrew J; Campbell, T Mark; Hopkinson, Devan; Kingsbury, Sarah R; Bowes, Mike A; Conaghan, Philip G

    2015-08-25

    Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. PROSPERO registration number: CRD 42013005009.

  7. A review of the clinical utility of duloxetine in the treatment of diabetic peripheral neuropathic pain

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    King JB

    2015-08-01

    Full Text Available Jordan B King, Marisa B Schauerhamer, Brandon K Bellows Pharmacotherapy Outcomes Research Center, University of Utah College of Pharmacy, Salt Lake City, UT, USA Abstract: Diabetes mellitus is a world-wide epidemic with many long-term complications, with neuropathy being the most common. In particular, diabetic peripheral neuropathic pain (DPNP, can be one of the most distressing complications associated with diabetes, leading to decreases in physical and mental quality of life. Despite the availability of many efficient medications, DPNP remains a challenge to treat, and the optimal sequencing of pharmacotherapy remains unknown. Currently, there are only three medications approved by the US Food and Drug Administration specifically for the management of DPNP. Duloxetine (DUL, a selective serotonin-norepinephrine reuptake inhibitor, is one of these. With the goal of optimizing pharmacotherapy use in DPNP population, a review of current literature was conducted, and the clinical utility of DUL described. Along with early clinical trials, recently published observational studies and pharmacoeconomic models may be useful in guiding decision making by clinicians and managed care organizations. In real-world practice settings, DUL is associated with decreased or similar opioid utilization, increased medication adherence, and similar health care costs compared with current standard of care. DUL has consistently been found to be a cost-effective option over short time-horizons. Currently, the long-term cost-effectiveness of DUL is unknown. Evidence derived from randomized clinical trials, real-world observations, and economic models support the use of DUL as a first-line treatment option from the perspective of the patient, clinician, and managed care payer. Keywords: clinical trials, pharmacoeconomic studies, opioid-utilization, health care utilization, pregabalin, tricyclic antidepressants, gabapentin

  8. Duloxetine compliance and its association with healthcare costs among patients with diabetic peripheral neuropathic pain.

    Science.gov (United States)

    Wu, N; Chen, S; Boulanger, L; Fraser, K; Bledsoe, S L; Zhao, Y

    2009-09-01

    Duloxetine is approved to treat diabetic peripheral neuropathic pain (DPNP) in the US. The study objective was to examine the predictors of duloxetine compliance, and its association with healthcare costs among DPNP patients. The study used administrative claims databases to identify non-depressed DPNP patients with a duloxetine prescription dispensed between October 1, 2004 and December 31, 2006. Two cohorts of patients were constructed based on compliance to duloxetine therapy over 1-year follow-up with high compliance defined as a medication possession ratio (MPR) > or =0.80. All-cause, diabetes-, and DPNP-related healthcare costs during 1-year follow-up were estimated. Logistic regressions were performed to examine how average daily dose (ADD) of duloxetine and other factors may influence compliance. Multivariate regressions were estimated to examine the association between compliance and healthcare costs. The study included 1,380 commercially insured (mean age 55 years) and 974 patients with employer-sponsored Medicare supplemental insurance (mean age 75 years). In both populations, patients with an ADD >30 mg were more likely to be compliant with the therapy compared with those with an ADD of compliance patients had greater all-cause ($5,334, pcosts ($3,414, pcompliance patients, with the biggest difference from inpatient costs (all-cause: $7,508; diabetes-related: $3,785, all pcosts were not significant. DPNP patients with a higher ADD of duloxetine over a 1-year follow-up period were more compliant with the therapy. Duloxetine patients with high compliance were also associated with lower healthcare costs. Due to the use of a retrospective cohort design on administrative claims database, limitations of this analysis include a lack of formal diagnostic testing of patients, and inability to infer causality or measure factors such as DPNP severity that are not captured in such database.

  9. Olesoxime (cholest-4-en-3-one, oxime): Analgesic and neuroprotective effects in a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel

    OpenAIRE

    Xiao, Wen Hua; Zheng, Felix Y.; Bennett, Gary J.; Bordet, Thierry; Pruss, Rebecca M.

    2009-01-01

    Olesoxime is a small cholesterol-like molecule that was discovered in a screening program aimed at finding treatment for amyotrophic lateral sclerosis and other diseases where motor neurons degenerate. In addition to its neuroprotective and pro-regenerative effects on motor neurons in vitro and in vivo, it has been shown to have analgesic effects in rat models of painful peripheral neuropathy due to vincristine and diabetes. We used a rat model of painful peripheral neuropathy produced by the...

  10. 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.

  11. Peripheral Pain-Sensing Neurons: from Molecular Diversity to Functional Specialization

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    Aziz Moqrich

    2014-01-01

    Full Text Available Recent work in Cell Reports by Minett et al. and Yang et al. highlights the complexity of pain pathways and points to new ways of thinking about chronic and disease-related pain.

  12. Self-reported pain severity, quality of life, disability, anxiety and depression in patients classified with 'nociceptive', 'peripheral neuropathic' and 'central sensitisation' pain. The discriminant validity of mechanisms-based classifications of low back (±leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-04-01

    Evidence of validity is required to support the use of mechanisms-based classifications of pain clinically. The purpose of this study was to evaluate the discriminant validity of \\'nociceptive\\' (NP), \\'peripheral neuropathic\\' (PNP) and \\'central sensitisation\\' (CSP) as mechanisms-based classifications of pain in patients with low back (±leg) pain by evaluating the extent to which patients classified in this way differ from one another according to health measures associated with various dimensions of pain. This study employed a cross-sectional, between-subjects design. Four hundred and sixty-four patients with low back (±leg) pain were assessed using a standardised assessment protocol. Clinicians classified each patient\\'s pain using a mechanisms-based classification approach. Patients completed a number of self-report measures associated with pain severity, health-related quality of life, functional disability, anxiety and depression. Discriminant validity was evaluated using a multivariate analysis of variance. There was a statistically significant difference between pain classifications on the combined self-report measures, (p = .001; Pillai\\'s Trace = .33; partial eta squared = .16). Patients classified with CSP (n = 106) reported significantly more severe pain, poorer general health-related quality of life, and greater levels of back pain-related disability, depression and anxiety compared to those classified with PNP (n = 102) and NP (n = 256). A similar pattern was found in patients with PNP compared to NP. Mechanisms-based pain classifications may reflect meaningful differences in attributes underlying the multidimensionality of pain. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  13. Increased Interleukin-6 Activity Associated with Painful Chemotherapy-Induced Peripheral Neuropathy in Women after Breast Cancer Treatment

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    Angela Starkweather

    2010-01-01

    Full Text Available Accumulating evidence suggests that neural-immune interactions are involved in the development of painful chemotherapy-induced peripheral neuropathy, particularly through the increased release of proinflammatory cytokines. The purpose of this study was used to evaluate levels of interleukin [IL]-6 and IL-6 receptors in women with breast cancer after the conclusion of chemotherapy who either had painful symptoms of chemotherapy-induced peripheral neuropathy (CIPN group, N=20 or did not experience CIPN symptoms (Comparison group, N=20. CIPN participants had significantly higher levels of IL-6 and soluble IL-6R (sIL-6R compared to women without CIPN symptoms (P<.001 for both. In addition, soluble gp130, which blocks the IL-6/sIL-6R complex from binding to gp130 within the cellular membrane, was significantly lower (P<.01. Circulating concentrations of sIL-6R were inversely correlated with the density of IL-6R on the cell surface of monocytes in the total sample (r=−.614,P=.005. These findings suggest that IL-6 transsignaling may be an important biological mechanism associated with the persistence of painful CIPN symptoms, with potential implications for symptom management and research.

  14. Role of peripheral sigma-1 receptors in ischaemic pain: Potential interactions with ASIC and P2X receptors.

    Science.gov (United States)

    Kwon, S G; Roh, D H; Yoon, S Y; Choi, S R; Choi, H S; Moon, J Y; Kang, S Y; Kim, H W; Han, H J; Beitz, A J; Oh, S B; Lee, J H

    2016-04-01

    The role of peripheral sigma-1 receptors (Sig-1Rs) in normal nociception and in pathologically induced pain conditions has not been thoroughly investigated. Since there is mounting evidence that Sig-1Rs modulate ischaemia-induced pathological conditions, we investigated the role of Sig-1Rs in ischaemia-induced mechanical allodynia (MA) and addressed their possible interaction with acid-sensing ion channels (ASICs) and P2X receptors at the ischaemic site. We used a rodent model of hindlimb thrombus-induced ischaemic pain (TIIP) to investigate their role. Western blot was performed to observe changes in Sig-1R expression in peripheral nervous tissues. MA was measured after intraplantar (i.pl.) injections of antagonists for the Sig-1, ASIC and P2X receptors in TIIP rats or agonists of each receptor in naïve rats. Sig-1R expression significantly increased in skin, sciatic nerve and dorsal root ganglia at 3 days post-TIIP surgery. I.pl. injections of the Sig-1R antagonist, BD-1047 on post-operative days 0-3 significantly attenuated the development of MA during the induction phase, but had no effect on MA when given during the maintenance phase (days 3-6 post-surgery). BD-1047 synergistically increased amiloride (an ASICs blocker)- and TNP-ATP (a P2X antagonist)-induced analgesic effects in TIIP rats. In naïve rats, i.pl. injection of Sig-1R agonist PRE-084 alone did not produce MA; but it did induce MA when co-administered with either an acidic pH solution or a sub-effective dose of αβmeATP. Peripheral Sig-1Rs contribute to the induction of ischaemia-induced MA via facilitation of ASICs and P2X receptors. Thus, peripheral Sig-1Rs represent a novel therapeutic target for the treatment of ischaemic pain. © 2015 European Pain Federation - EFIC®

  15. Examining Changes in Central and Peripheral Pain as Mediates of Fatigue Improvement: Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

    Science.gov (United States)

    Druce, Katie L; Jones, Gareth T; Macfarlane, Gary J; Basu, Neil

    2016-07-01

    Following anti-tumor necrosis factor (anti-TNF) therapy, improvements in rheumatoid arthritis (RA) fatigue are driven by reductions in pain. However, therapies may modify both central and peripheral pain. This study sought to examine the hypothesis that reductions in fatigue after anti-TNF therapy reflect changes in central, not peripheral, pain mechanisms. Data came from patients with severe baseline fatigue (Short Form 36 health survey [SF-36] vitality scale ≤12.5; n = 2,652), recruited to the British Society for Rheumatology Biologics Register for RA for commencing anti-TNF therapies between October 2000 and November 2008. Data of interest comprised change over 6 months in fatigue, pain (SF-36 bodily pain scale), and disease activity constituents (Disease Activity Score in 28 joints, erythrocyte sedimentation rate [ESR], global health, swollen joints, and tender joints). Principal components factor analysis with varimax rotation determined latent variables of symptom change; variables were accepted provided they had eigenvalues ≥1. Six factors were identified, of which 2 met acceptance criteria (eigenvalues of 2.39 and 1.14, respectively). Following rotation, loadings indicated that factor 1 comprised markers of peripheral inflammation: change in ESR, swollen joints, tender joints, and global health. This distinct loading led to factor 1 being labeled peripheral inflammation. Conversely, factor 2 comprised change in pain, fatigue, and global health and an absence of peripheral inflammation markers and was therefore labeled central inflammation. Following anti-TNF therapies, reductions in fatigue and pain appear to reflect improvements in central, rather than peripheral, inflammation. Therefore, for those seeking to treat fatigue via pain mechanisms, improvements may be maximized by the application of treatment modalities that effectively target central mechanisms. © 2016, American College of Rheumatology.

  16. Improved foot sensitivity and pain reduction in patients with peripheral neuropathy after treatment with monochromatic infrared photo energy--MIRE.

    Science.gov (United States)

    Harkless, Lawrence B; DeLellis, Salvatore; Carnegie, Dale H; Burke, Thomas J

    2006-01-01

    The medical records of 2239 patients (mean age=73 years) with established peripheral neuropathy (PN) were examined to determine whether treatment with MIRE was, in fact, associated with increased foot sensitivity to the Semmes Weinstein monofilament (SWM) 5.07 and a reduction in neuropathic pain. The PN in 1395 of these patients (62%) was due to diabetes. Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1+/-2.9 were insensitive to the SWM 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot. After treatment, the number of insensate sites on both feet decreased to 2.4+/-2.6, an improvement of 66%. Of the 2078 (93%) patients initially presenting with loss of protective sensation, 1106 (53%) no longer had loss of protective sensation after treatment (P<.0001); 1563 patients (70%) also exhibited neuropathic pain in addition to sensory impairment. Prior to treatment with MIRE, pain measured on the 11-point visual analogue scale (VAS) was 7.2+/-2.2 points, despite the use of a variety of pain-relieving therapeutic agents. After treatment with MIRE, pain was reduced by 4.8+/-2.4 points, a 67% reduction. Therefore, MIRE appears to be associated with significant clinical improvement in foot sensation and, simultaneously, a reduction in neuropathic pain in a large cohort of primarily Medicare aged, community-dwelling patients, initially diagnosed with PN. The quality of life associated with these two outcomes cannot be underappreciated.

  17. Cingulate Alpha-2A Adrenoceptors Mediate the Effects of Clonidine on Spontaneous Pain Induced by Peripheral Nerve Injury

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    Yong-Jie Wang

    2017-09-01

    Full Text Available The anterior cingulate cortex (ACC is an important brain area for the regulation of neuropathic pain. The α2A adrenoceptor is a good target for pain management. However, the role of cingulate α2A adrenoceptors in the regulation of neuropathic pain has been less studied. In this study, we investigated the involvement of cingulate α2A adrenoceptors in the regulation of neuropathic pain at different time points after peripheral nerve injury in mice. The application of clonidine, either systemically (0.5 mg/kg intraperitoneally or specifically to the ACC, increased paw withdrawal thresholds (PWTs and induced conditioned place preference (CPP at day 7 after nerve injury, suggesting that cingulate α2 adrenoceptors are involved in the regulation of pain-like behaviors. Quantitative real-time PCR data showed that α2A adrenoceptors are the dominant α2 adrenoceptors in the ACC. Furthermore, the expression of cingulate α2A adrenoceptors was increased at day 3 and day 7 after nerve injury, but decreased at day 14, while no change was detected in the concentration of adrenaline or noradrenaline. BRL-44408 maleate, a selective antagonist of α2A adrenoceptors, was microinfused into the ACC. This blocking of cingulate α2A adrenoceptors activity abolished the CPP induced by clonidine (0.5 mg/kg intraperitoneally but not the effects on PWTs at day 7. However, clonidine applied systemically or specifically to the ACC at day 14 increased the PWTs but failed to induce CPP; this negative effect was reversed by the overexpression of cingulate α2A adrenoceptors. These results suggest that cingulate α2A adrenoceptors are necessary for the analgesic effects of clonidine on spontaneous pain.

  18. The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model.

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    Qi-Liang Mao-Ying

    Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN characterized by loss of sensory sensitivity and pain in hands and feet is the major dose-limiting toxicity of many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin is the most widely used prescription drug in the world and improves glycemic control in diabetes patients. There is some evidence that metformin enhances the efficacy of cancer treatment. The aim of this study was to test the hypothesis that metformin protects against chemotherapy-induced neuropathic pain and sensory deficits. Mice were treated with cisplatin together with metformin or saline. Cisplatin induced increased sensitivity to mechanical stimulation (mechanical allodynia as measured using the von Frey test. Co-administration of metformin almost completely prevented the cisplatin-induced mechanical allodynia. Co-administration of metformin also prevented paclitaxel-induced mechanical allodynia. The capacity of the mice to detect an adhesive patch on their hind paw was used as a novel indicator of chemotherapy-induced sensory deficits. Co-administration of metformin prevented the cisplatin-induced increase in latency to detect the adhesive patch indicating that metformin prevents sensory deficits as well. Moreover, metformin prevented the reduction in density of intra-epidermal nerve fibers (IENFs in the paw that develops as a result of cisplatin treatment. We conclude that metformin protects against pain and loss of tactile function in a mouse model of CIPN. The finding that metformin reduces loss of peripheral nerve endings indicates that mechanism underlying the beneficial effects of metformin includes a neuroprotective activity. Because metformin is widely used for treatment of type II diabetes, has a broad safety profile, and is currently being tested as an adjuvant drug in cancer treatment, clinical translation of these findings could be rapidly achieved.

  19. Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia

    DEFF Research Database (Denmark)

    Ge, H-Y; Nie, Hongling; Graven-Nielsen, Thomas

    2012-01-01

    OBJECTIVE: Sustained isometric muscle contraction (fatiguing contraction) recruits segmental and/or extrasegmental descending inhibition in healthy subjects but not in fibromyalgia (FM). We hypothesized that fatiguing contraction may shift descending pain modulation from inhibition towards...

  20. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.

    Science.gov (United States)

    Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina

    2016-09-08

    Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.

  1. Investigation of Peripheral Effects of Citrus Limon Essential Oil on Somatic Pain in Male Wistar Rats: Role of Histaminergic System

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    Ali Mojtahedin

    2016-12-01

    Full Text Available Background & Objective: One of the plants used in traditional medicine is lemon which has analgesic effect. However, little research has been performed on the analgesic effect of lemon and mechanisms of action with an emphasis on neurotransmitters systems. Therefore, the present study set to investigate the peripheral effects of lemon essential oil on somatic pain using formalin test with an emphasis on histaminergic system in male Wistar rats. Materiala & Methods: Sixty male rats weighing approximately 200-250g and aged 14-16 wk were divided into 10 groups: sham (Salin + Formalin 1% intraplantar, three treatment groups with lemon essential oil (EO (12.5, 25 and 50 mg/kg, three treatment groups with Chlorpheniramine (5, 10 and 20 mg/kg, 1 treatment group with Histamine (10 mg/kg, 1 pretreatment group with Chlorpheniramine (20 mg/kg + EO (50mg/kg, and 1 pretreatment group with Histamine (10 mg/kg + EO (50 mg/kg. Formalin test was used to assess somatic pain. Data analysis was performed using one-way ANOVA. Results:  Intraperitoneal injection of lemon essential oil reduced the pain response induced by formalin in both phases (P<0.05. Pretreatment with chlorpheniramine and lemon essential oil enhanced the analgesic response in both phases (P<0.05. Conclusion: Lemon essential oil had analgesic effects, probably caused by the histaminergic system.

  2. Dynamics of circadian thalamocortical flow of information during a peripheral neuropathic pain condition

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    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.

  3. Feasibility of Topical Applications of Natural High-Concentration Capsaicinoid Solutions in Patients with Peripheral Neuropathic Pain: A Retrospective Analysis

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    Fanny Bauchy

    2016-01-01

    Full Text Available Background. Capsaicin, one of several capsaicinoid compounds, is a potent TRPV1 agonist. Topical application at high concentration (high concentration, >1% induces a reversible disappearance of epidermal free nerve endings and is used to treat peripheral neuropathic pain (PNP. While the benefit of low-concentration capsaicin remains controversial, the 8%-capsaicin patch (Qutenza®, 2010, Astellas, Netherlands has shown its effectiveness. This patch is, however, costly and natural high-concentration capsaicinoid solutions may represent a cheaper alternative to pure capsaicin. Methods. In this retrospective study, 149 patients were screened, 132 were included with a diagnosis of neuropathic pain, and eighty-four were retained in the final analyses (median age: 57.5 years [IQR25–75: 44.7–67.1], male/female: 30/54 with PNP who were treated with topical applications of natural high-concentration capsaicinoid solutions (total number of applications: 137. Indications were postsurgical PNP (85.7% and nonsurgical PNP (14.3% (posttraumatic, HIV-related, postherpetic, and radicular PNP. Objectives. To assess the feasibility of topical applications of natural high-concentration capsaicinoid solutions for the treatment of PNP. Results. The median treated area was 250 cm2 [IQR25–75: 144–531]. The median amount of capsaicinoids was 55.1 mg [IQR25–75: 28.7–76.5] per plaster and the median concentration was 172.3 μg/cm2 [IQR25–75: 127.6–255.2]. Most patients had local adverse effects on the day of treatment, such as mild to moderate burning pain and erythema. 13.6–19.4% of the patients experienced severe pain or erythema. Following treatment, 62.5% of patients reported a lower pain intensity or a smaller pain surface, and 35% reported a sustained pain relief lasting for at least 4 weeks. Conclusion. Analgesic topical treatment with natural high-concentration capsaicinoid is feasible and may represent a low cost alternative to alleviate

  4. Cross-Excitation in Peripheral Sensory Ganglia Associated with Pain Transmission

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    Katsuhiro Omoto

    2015-08-01

    Full Text Available Despite the absence of synaptic contacts, cross-excitation of neurons in sensory ganglia during signal transmission is considered to be chemically mediated and appears increased in chronic pain states. In this study, we modulated neurotransmitter release in sensory neurons by direct application of type A botulinum neurotoxin (BoNT/A to sensory ganglia in an animal model of neuropathic pain and evaluated the effect of this treatment on nocifensive. Unilateral sciatic nerve entrapment (SNE reduced the ipsilateral hindpaw withdrawal threshold to mechanical stimulation and reduced hindpaw withdrawal latency to thermal stimulation. Direct application of BoNT/A to the ipsilateral L4 dorsal root ganglion (DRG was localized in the cell bodies of the DRG and reversed the SNE-induced decreases in withdrawal thresholds within 2 days of BoNT/A administration. Results from this study suggest that neurotransmitter release within sensory ganglia is involved in the regulation of pain-related signal transmission.

  5. Population analyses of efficacy and safety of ABT-594 in subjects with diabetic peripheral neuropathic pain.

    Science.gov (United States)

    Dutta, Sandeep; Hosmane, Balakrishna S; Awni, Walid M

    2012-06-01

    ABT-594, a neuronal nicotinic acetylcholine receptor ligand, is 30- to 100-fold more potent than morphine in animal models of nociceptive and neuropathic pain. Efficacy and safety of ABT-594 in subjects with painful diabetic polyneuropathy was evaluated in a phase 2 study. The objective of this work was to use a nonlinear mixed effects model-based approach for characterizing the relationship between dose and response (efficacy and safety) of ABT-594. Subjects (N = 266) were randomized into four groups in a double-blind, placebo-controlled, 7-week study to receive twice daily regimens of placebo or 150, 225, and 300 μg of ABT-594. The primary efficacy variable, pain score (11-point Likert scale), was assessed on five occasions. The probability of change from baseline pain score of ≥1, ≥2, and ≥3 was modeled using cumulative logistic regression with dose and days of treatment as explanatory variables. The incidence of five most frequently occurring adverse events (AEs) was modeled using linear logistic regression. ABT-594 ED(50) values (improvement in 50% of subjects) for improvement in pain scores of ≥1, ≥2, and ≥3 were 50, 215, and 340 μg, respectively, for the average number of days (33) on treatment. The rank order of ED(50) values for AEs was nausea, vomiting, dizziness, headache, and abnormal dreams; nicotine users were less sensitive to AEs. Population pharmacodynamic models developed to characterize the improvement in pain score and incidence of adverse events indicate an approximately twofold separation between the ED(50) values for efficacy and AEs.

  6. Profound and persistent painful paclitaxel peripheral neuropathy in a premenopausal patient

    OpenAIRE

    Quintyne, K I; Mainstone, P; McNamara, B; Boers, P; Wallis, F; Gupta, R K

    2011-01-01

    The authors herein report the case of a 35-year-old woman undergoing adjuvant therapy for node positive breast cancer, who presented with short and rapidly progressive history of bilateral lower limb symptoms of peripheral neuropathy following therapy with paclitaxel. MRI of her neural axis revealed no leptomeningeal enhancement or focal metastatic lesions. Neurophysiological tests favoured toxic sensory axonal polyneuropathy. She remains symptomatic following discontinuation of therapy 20 mo...

  7. Circulating Angiogenic Growth Factors in Diabetes Patients with Peripheral Arterial Disease and Exertional Leg Pain in Ghana

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    Kwame Yeboah

    2017-01-01

    Full Text Available Objective. Peripheral arterial disease (PAD is a common complication of diabetes, associated with impairment in angiogenesis. Angiogenesis is regulated by angiogenic growth factors such as angiopoietin 1 (Ang-1, Ang-2, and vascular endothelial growth factor (VEGF. We studied the association between angiogenic growth factors versus PAD and exertional leg symptoms in diabetes patients in Ghana. Method. In this cross-sectional study, ankle-brachial index was measured with oscillometrically and exertional leg symptoms were screened with Edinburgh claudication questionnaire in 140 diabetes patients and 110 nondiabetes individuals. Circulating levels of Ang-1, Ang-2, and VEGF were measured with immunosorbent assay. Results. The prevalence of PAD and exertional leg pain was 16.8% and 24.8%, respectively. Compared to non-PAD participants, PAD patients had higher VEGF levels [85.8 (37.5–154.5 versus 57.7 (16.6–161.1 p=0.032] and lower Ang-1 levels [31.3 (24.8–42.6 versus 40.9 (28.2–62.1, p=0.017]. In multivariable logistic regression, patients with exertional leg pain had increased the odds of plasma Ang-2 levels [OR (95% CI: 2.08 (1.08–6.41, p=0.036]. Conclusion. Diabetes patients with PAD and exertional leg pain have imbalance in angiogenic growth factors, indicating impaired angiogenesis. In patients with exertional leg pains, Ang-2 may be an important biomarker.

  8. Cytidine 5’-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats

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    Emril DR

    2016-05-01

    Full Text Available Dessy R Emril,1 Samekto Wibowo,2 Lucas Meliala,2 Rina Susilowati3 1Department of Neurology, Faculty of Medicine, Syiah Kuala University, Banda Aceh, 2Department of Neurology, 3Department of Histology and Cell Biology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, IndonesiaBackground: Cytidine 5’-diphosphocholine (citicoline has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury.Methods: Forty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 µmol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT tests were used to assess motoric function.Results: The crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17 compared with the crush/saline group (53.33%, n=15, P<0.005. The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P<0.001. However, the sciatic functional index analysis did not show significant differences between groups (P=0.35. The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18 and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume.Conclusion: In situ administration of 0.4 mL of 100 μmol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery

  9. Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study.

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    Tomasello, Caterina; Pinto, Rita Maria; Mennini, Chiara; Conicella, Elena; Stoppa, Francesca; Raucci, Umberto

    2018-04-06

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy, in need of effective treatment. Preliminary data support the efficacy of scrambler therapy (ST), a noninvasive cutaneous electrostimulation device, in adults with CIPN. We test the efficacy, safety, and durability of ST for neuropathic pain in adolescents with CIPN. We studied nine pediatric patients with cancer and CIPN who received ST for pain control. Each patient received 45-min daily sessions for 10 consecutive days as a first step, but some of them required additional treatment. Pain significantly improved comparing Numeric Rate Scale after 10 days of ST (9.22 ± 0.83 vs. 2.33 ± 2.34; P < 0.001) and at the end of the optimized cycle (EOC) (9.22 ± 0.83 vs. 0.11 ± 0.33, P < 0.001). The improvement in quality of life was significantly reached on pain interference with general activity (8.67 ± 1.66 vs. 3.33 ± 2.12, P < 0.0001), mood (8.33 ± 3.32 vs. 2.78 ± 2.82, P < 0.0005), walking ability (10.00 vs. 2.78 ± 1.22, P < 0.0001), sleep (7.56 ± 2.24 vs. 2.67 ± 1.41, P < 0.001), and relations with people (7.89 ± 2.03 vs. 2.11 ± 2.03, P < 0.0002; Lansky score 26.7 ± 13.2 vs. 10 days of ST 57.8 ± 13.9, P < 0.001; 26.7 ± 13.2 vs. EOC 71.1 ± 16.2, P < 0.001). Based on these preliminary data, ST could be a good choice for adolescents with CIPN for whom pain control is difficult. ST caused total relief or dramatic reduction in CIPN pain and an improvement in quality of life, durable in follow-up. It caused no detected side effects, and can be retrained successfully. Further larger studies should be performed to confirm our promising preliminary data in pediatric patients with cancer. © 2018 Wiley Periodicals, Inc.

  10. Are there abnormalities in peripheral and central components of somatosensory evoked potentials in non - specific chronic low back pain ?

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    Christian Puta

    2016-10-01

    Full Text Available Chronic low back pain (CLBP was shown to be associated with longer reflex response latencies of trunk muscles during external upper limb perturbations. One theoretical, but rarely investigated possibility for longer reflex latencies might be related to modulated somatosensory information processing. Therefore, the present study investigated somatosensory evoked potentials (SEPs to median nerve stimulation in CLBP patients and healthy controls (HC. Latencies of the peripheral N9 SEP component were used as primary outcome. In addition, latencies and amplitudes of the central N20 SEP component, sensory thresholds, motor thresholds, and nerve conduction velocity were also analyzed in CLBP patients and HC. There is a trend for the CLBP patients to exhibited longer N9 latencies at the ipsilateral Erb’s point compared to HC. This trend is substantiated by significantly longer N9 latencies in CLBP patients compared to normative data. None of the other parameters showed any significant difference between CLBP patients and HC. Overall, our data indicate small differences of the peripheral N9 SEP component; however, these differences cannot explain the reflex delay observed in CLBP patients. While it was important to rule out the contribution of early somatosensory processing and to elucidate its contribution to the delayed reflex responses in CLBP patients, further research is needed to find the primary source(s of time-delayed reflexes in CLBP.

  11. Frequencies of different peripheral nervous system pathologies among Cases of Lumbar Radicular Pain using Electrodiagnostic Studies

    International Nuclear Information System (INIS)

    Ayaz, S.; Waheed, A.; Ali, L.

    2014-01-01

    Objective: to discover the spectrum of diagnoses on nerve conduction studies/ Electromyography in patients with lumbar radicular pain, test preponderance of the commonest pathology and correlate commonest pathology with age > 50 years, gender and unilateral involvement. Study design: A descriptive cross-sectional study of 539 patients. Place and Duration of the study: the department of Electrodiagnostic studies, Armed Forces Institute of Rehabilitation Medicine, Rawalpindi from January 2012 to December 2012. Material and methods: using non-probability consecutive sampling 539 patients referred with complaints of lumbar radicular pain were subjected to electrodiagnostic evaluation for presence of lumbosacral radiculopathy, polyneuropathy, sciatic nerve injury or a combination of these. The preponderance of commonest pathology was tested statistically. The frequencies were then related statistically to age > 50 years, gender and unilateral or bilateral involvement. Result: A total of 539 patients (age:18-85 years) were registered. 355 (66% ) were males and 261 (48.4%) patients were > 50 years. Nerve conduction studies/Electromyography findings were abnormal in 386 (77.6%) patients. The commonest diagnosis was lumbosacral radiculopathy in 65% followed by polyneuropathy with superimposed lumbosacral radiculopathy in 7%. The preponderance of lumbosacral radiculopathy was statistically found significant (p 50 years. Conclusion: Lumbosacral radiculopathy is highly expected to be found on nerve conduction studies /electromyography in patients who present with lumbar radicular pain. The lumbosacral radiculopathy is more common in individuals of age 50 years and above. (author)

  12. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

    Science.gov (United States)

    Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  13. An interesting case of peripheral vascular disease, vascular reperfusion, and subsequent development of pain due to Paget's disease of bone.

    Science.gov (United States)

    Kwun, Sunna; Tucci, Joseph R

    2013-01-01

    To present a case of Paget's disease of bone that was unmasked after vascular reperfusion. In this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget's disease and peripheral vascular disease. A 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget's disease of bone, which was subsequently confirmed by imaging. This patient's development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget's disease of bone.

  14. Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

    Science.gov (United States)

    O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

    2015-09-01

    Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of

  15. Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain

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    Le Trong

    2009-02-01

    Full Text Available Abstract Background Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP. Approved or recommended drugs in this indication include duloxetine (DLX, pregabalin (PGB, gabapentin (GBP and amitriptyline (AMT. We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator. Methods We searched PubMed, EMBASE, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs assessing DLX, PGB, GBP and AMT in DPNP. Study arms using approved dosages with assessments after 5–13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24 h PS for all three drugs, and response rate (≥ 50% pain reduction and Patient Global Impression of Improvement/Change (PGI-I/C for DLX and PGB only. Tolerability criteria included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Direct comparisons versus placebo were conducted with pooled fixed – and random-effects analyses on endpoints reported in at least two studies of each drug. Indirect comparisons were performed between DLX and each of PGB and GBP using Bayesian simulation. Results Three studies of DLX, six of PGB, two of GBP and none of AMT met the inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and GBP, all were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences. Conclusion From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine

  16. Cost-effectiveness of duloxetine versus routine treatment for U.S. patients with diabetic peripheral neuropathic pain.

    Science.gov (United States)

    Wu, Eric Q; Birnbaum, Howard G; Mareva, Milena N; Le, T Kim; Robinson, Rebecca L; Rosen, Amy; Gelwicks, Steve

    2006-06-01

    The purpose of this study was to compare the cost-effectiveness of duloxetine versus routine treatment in management of diabetic peripheral neuropathic pain (DPNP). Two hundred thirty-three patients with DPNP who completed a 12-week, double-blind, placebo-controlled, randomized, multicenter duloxetine trial were re-randomized into a 52-week, open-label trial of duloxetine 60 mg twice daily versus routine treatment. Routine treatment included pain management therapies. Effectiveness was measured by using the bodily pain domain (BP) of the Medical Outcomes Study Short Form 36 (SF-36). Costs were analyzed from 3 perspectives: third party payer (direct medical costs), employer (direct and indirect medical costs), and societal (patient's out-of-pocket costs and total medical costs). Costs of study medications were not included because of limited data. Bootstrap method was applied to calculate statistical inference of the incremental cost-effectiveness ratio (ICER). Routine treatment most frequently used included gabapentin (56%), venlafaxine (36%), and amitripytline (15%). From employer and societal perspectives, duloxetine was cost-effective (ICER= -342 dollars and -429 dollars, respectively, per unit of SF-36 BP; both P

  17. Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome.

    Science.gov (United States)

    Shinoda, Masamichi; Takeda, Mamoru; Honda, Kuniya; Maruno, Mitsuru; Katagiri, Ayano; Satoh-Kuriwada, Shizuko; Shoji, Noriaki; Tsuchiya, Masahiro; Iwata, Koichi

    2015-12-01

    Burning mouth syndrome is characterized by altered sensory qualities, namely tongue pain hypersensitivity. We found that the mRNA expression of Artemin (Artn) in the tongue mucosa of patients with burning mouth syndrome was significantly higher than that of control subjects, and we developed a mouse model of burning mouth syndrome by application of 2,4,6-trinitrobenzene sulfonic acid (TNBS) diluted with 50% ethanol to the dorsum of the tongue. TNBS treatment to the tongue induced persistent, week-long, noninflammatory tongue pain and a significant increase in Artn expression in the tongue mucosa and marked tongue heat hyperalgesia. Following TNBS treatment, the successive administration of the transient receptor potential vanilloid 1 (TRPV1) antagonist SB366791 or neutralizing anti-Artn antibody completely inhibited the heat hyperalgesia. The number of glial cell line-derived neurotrophic factor family receptor α3 (GFRα3)-positive and TRPV1-positive trigeminal ganglion (TG) neurons innervating the tongue significantly increased following TNBS treatment and was significantly reduced by successive administration of neutralizing anti-Artn antibody. The capsaicin-induced current in TG neurons innervating the tongue was enhanced following TNBS treatment and was inhibited by local administration of neutralizing anti-Artn antibody to the tongue. These results suggest that the overexpression of Artn in the TNBS-treated tongue increases the membrane excitability of TG neurons innervating the tongue by increasing TRPV1 sensitivity, which causes heat hyperalgesia. This model may be useful for the study of tongue pain hypersensitivity associated with burning mouth syndrome.

  18. Real-life efficacy of pregabalin for the treatment of peripheral neuropathic pain in daily clinical practice in Denmark: the NEP-TUNE study

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    Crawford ME

    2016-05-01

    Full Text Available Michael E Crawford,1 Peter Bo Poulsen,2 Berit Schiøttz-Christensen,3 Andreas Habicht,4 Mette Strand,2 Flemming W Bach5 1Copenhagen City Pain Clinic, Copenhagen K, 2Pfizer Denmark ApS, Ballerup, 3Spine Center Southern Denmark, Lillebælt Hospital, Middelfart, 4Signifikans ApS, Vedbæk, 5Department of Neurology, Aalborg University Hospital, Aalborg, Denmark Objective: The aim of this study was to provide evidence regarding the real-life efficacy of pregabalin in the treatment of peripheral neuropathic pain (NeP in Denmark. Methods: In this prospective, observational, noninterventional study, pregabalin (Lyrica® was prescribed following usual clinical practice. Compared with baseline, the primary study end points after 3 months of observation were changes in 1 the average level of pain during the past week, 2 the worst level of pain during the past week, and 3 the least level of pain during the past week. The Wilcoxon signed-rank test was used to perform paired analyses, and a multivariate regression analysis investigated factors driving change in pain. Results: A total of 86 of the 128 patients included were regarded as efficacy evaluable (those completing 3 months of pregabalin treatment. Patients (59 years were long-time sufferers of peripheral NeP, and 38% of them had comorbidities. The majority had previously been treated with tricyclic antidepressants or gabapentin. The average dose of pregabalin was 81.5 mg/d at baseline and 240 mg/d after 3 months. A clinically and statistically significant improvement of 2.2 points in the average level of pain intensity was found after 3 months. The higher the pain intensity at baseline, the higher was the reduction of the pain score. Positive results were also found for pain-related sleep interference, patients’ global impression of change, quality of life, and work and productivity impairment. Twenty-one patients reported 28 adverse events. Conclusion: This real-life study indicates that for some

  19. The involvement of peripheral alpha 2-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain.

    Science.gov (United States)

    Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Paranos, Sonja Lj; Prostran, Milica S; Bosković, Bogdan

    2007-11-01

    We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.pl.), BRL 44408 (100 and 200 nmol/paw; i.pl.) and MK-912 (10 and 20 nmol/paw; i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/paw; i.pl.) in a dose-dependent manner. The effects of antagonists were due to local effects since they were not observed after administration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED(50) (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. Isobolographic analysis revealed an additive antihyperalgesic effect. Our results indicate that the peripheral alpha2A and alpha2C adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia.

  20. Delayed ethylene glycol poisoning presenting with abdominal pain and multiple cranial and peripheral neuropathies: a case report

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    Sran Hersharan

    2010-07-01

    Full Text Available Abstract Introduction Ethylene glycol poisoning may pose diagnostic difficulties if the history of ingestion is not volunteered, or if the presentation is delayed. This is because the biochemical features of high anion-gap metabolic acidosis and an osmolar gap resolve within 24 to 72 hours as the ethylene glycol is metabolized to toxic metabolites. This case illustrates the less well-known clinical features of delayed ethylene glycol poisoning, including multiple cranial and peripheral neuropathies, and the clinical findings which may point towards this diagnosis in the absence of a history of ingestion. Case presentation A 53-year-old Afro-Caribbean man presented with vomiting, abdominal pain and oliguria, and was found to have acute renal failure requiring emergency hemofiltration, and raised inflammatory markers. Computed tomography imaging of the abdomen revealed the appearance of bilateral pyelonephritis, however he failed to improve with broad-spectrum antibiotics, and subsequently developed multiple cranial neuropathies and increasing obtundation, necessitating intubation and ventilation. Computed tomography of the brain showed no focal lesions, and a lumbar puncture revealed a raised cerebrospinal fluid opening pressure and cyto-albuminological dissociation. Nerve conduction studies revealed a sensorimotor radiculoneuropathy mimicking a Guillain-Barre type lesion with an atypical distribution. It was only about two weeks after presentation that the history of ethylene glycol ingestion one week before presentation was confirmed. He had a slow recovery on the intensive care unit, requiring renal replacement therapy for eight weeks, and complicated by acute respiratory distress syndrome, neuropathic pain and a slow neurological recovery requiring prolonged rehabilitation. Conclusions Although neuropathy as a result of ethylene glycol poisoning has been described in a few case reports, all of these were in the context of a known history of

  1. First do no harm: pain relief for the peripheral venous cannulation of adults, a systematic review and network meta-analysis.

    Science.gov (United States)

    Bond, Mary; Crathorne, Louise; Peters, Jaime; Coelho, Helen; Haasova, Marcela; Cooper, Chris; Milner, Quentin; Shawyer, Vicki; Hyde, Christopher; Powell, Roy

    2016-10-01

    Peripheral venous cannulation is an everyday practice in hospitals, which many adults find painful. However, anaesthesia for cannulation is usually only offered to children. Inadequate pain relief is not only unpleasant for patients but may cause anxiety about further treatment and deter patients from seeking medical care in the future. The aim of this study is to discover the most effective local anaesthetic for adult peripheral venous cannulation and to find out how the pain of local anaesthetic application compares with that of unattenuated cannulation. These aims are addressed through a systematic review, network meta-analysis and random-effects meta-analysis. Searching covered 12 databases including MEDLINE and EMBASE from 1990 to August 2015. The main included study design was RCTs. The primary outcome measure is self-reported pain, measured on a 100 mm visual analogue scale. The systematic review found 37 includable studies, 27 of which were suitable for network meta-analysis and two for random-effects meta-analysis. The results of the network meta-analysis indicate that none of the 17 anaesthetic considered had a very high probability of being the most effective when compared to each other; 2 % lidocaine had the highest probability (44 %). When the anaesthetics were compared to no treatment, the network meta-analysis showed that again 2 % lidocaine was estimated to be the most effective (mean difference -25.42 (95 % CI -32.25, -18.57). Other members of the 'caine' family were also estimated to be more effective than no treatment as were Ametop ® , EMLA ® and Rapydan ® patch. The meta-analysis compared the pain of anaesthetic application with the unattenuated pain of cannulation. This found that all applications of local anaesthetic were less painful than cannulation without local anaesthetic. In particular a 1 % lidocaine injection was estimated to be -12.97 (95 % CI -15.71, -10.24) points (100 mm VAS) less painful than unattenuated cannulation

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

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    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

  3. Impact of comorbid depression or anxiety on patterns of treatment and economic outcomes among patients with diabetic peripheral neuropathic pain.

    Science.gov (United States)

    Boulanger, Luke; Zhao, Yang; Foster, Talia S; Fraser, Kimberly; Bledsoe, Stacey L; Russell, Mason W

    2009-07-01

    The objective of this retrospective analysis was to assess the correlation of comorbid depression and/or anxiety to patterns of treatment, healthcare utilization, and associated costs among diabetic peripheral neuropathic pain (DPNP) patients, employing a large US administrative claims database. Patients under age 65 with commercial insurance and patients aged 65 and older with employer-sponsored Medicare supplemental insurance were selected for the study if they had at least one diagnosis of DPNP in 2005. The first observed DPNP claim was considered the 'index date.' All individuals had a 12-month pre-index and 12-month follow-up period. For both populations, two subgroups were constructed for individuals with depression and/or anxiety (DPNP-DA cohort) or without these disorders (DPNP-only cohort). Patients' demographic characteristics, clinical characteristics, and medication use were compared over the pre-index period. Healthcare expenditures and resource utilization were measured for the post-index period. Two-part models were used to examine the impact of comorbid depression and/or anxiety on healthcare utilization and costs, controlling for demographic and clinical characteristics. The study identified 11,854 DPNP-only and 1512 DPNP-DA patients in the Medicare supplemental cohort, and 11,685 and 2728 in the commercially insured cohort. Compared to DPNP-only patients over the follow-up period, a significantly higher percentage of DPNP-DA patients were dispensed pain and DPNP-related medication. All components of healthcare utilization, except home healthcare visits and physician office visits, were more likely to be provided to DPNP-DA patients versus the DPNP-only cohort (all p bias between study cohorts, mis-identification of DPNP and/or depression, and inability to assess indirect costs as well as use and cost of over-the-counter medications. These findings indicate that the healthcare costs were significantly higher for DPNP patients comorbid with

  4. Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN

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    Annalisa Canta

    2015-06-01

    Full Text Available The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN. This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy.

  5. Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

    Science.gov (United States)

    Canta, Annalisa; Pozzi, Eleonora; Carozzi, Valentina Alda

    2015-01-01

    The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy. PMID:29056658

  6. 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

  7. A Cost-Consequences analysis of the effect of Pregabalin in the treatment of peripheral Neuropathic Pain in routine medical practice in Primary Care settings

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    Torrades Sandra

    2011-01-01

    Full Text Available Abstract Background Neuropathic pain (NeP is a common symptom of a group of a variety of conditions, including diabetic neuropathy, trigeminal neuralgia, or postherpetic neuralgia. Prevalence of NeP has been estimated to range between 5-7.5%, and produces up to 25% of pain clinics consultations. Due to its severity, chronic evolution, and associated co-morbidities, NeP has an important individual and social impact. The objective was to analyze the effect of pregabalin (PGB on pain alleviation and longitudinal health and non-health resources utilization and derived costs in peripheral refractory NeP in routine medical practice in primary care settings (PCS in Spain. Methods Subjects from PCS were older than 18 years, with peripheral NeP (diabetic neuropathy, post-herpetic neuralgia or trigeminal neuralgia, refractory to at least one previous analgesic, and included in a prospective, real world, and 12-week two-visit cost-of-illness study. Measurement of resources utilization included both direct healthcare and indirect expenditures. Pain severity was measured by the Short Form-McGill Pain Questionnaire (SF-MPQ. Results One-thousand-three-hundred-fifty-four PGB-naive patients [58.8% women, 59.5 (12.7 years old] were found eligible for this secondary analysis: 598 (44% switched from previous therapy to PGB given in monotherapy (PGBm, 589 (44% received PGB as add-on therapy (PGB add-on, and 167 (12% patients changed previous treatments to others different than PGB (non-PGB. Reductions of pain severity were higher in both PGBm and PGB add-on groups (54% and 51%, respectively than in non-PGB group (34%, p Conclusion In Spanish primary care settings, PGB given either add-on or in monotherapy in routine medical practice was associated with pain alleviation leading to significant longitudinal reductions in resource use and total costs during the 12-week period of the study compared with non-PGB-therapy of patients with chronic NeP of peripheral origin

  8. Dose Titration of Pregabalin in Patients with Painful Diabetic Peripheral Neuropathy: Simulation Based on Observational Study Patients Enriched with Data from Randomized Studies.

    Science.gov (United States)

    Alexander, Joe; Edwards, Roger A; Manca, Luigi; Grugni, Roberto; Bonfanti, Gianluca; Emir, Birol; Whalen, Edward; Watt, Stephen; Parsons, Bruce

    2018-03-01

    Achieving a therapeutic response to pregabalin in patients with painful diabetic peripheral neuropathy (pDPN) requires adequate upward dose titration. Our goal was to identify relationships between titration and response to pregabalin in patients with pDPN. Data were integrated from nine randomized, placebo-controlled clinical trials as well as one 6-week open-label observational study conducted by 5808 physicians (2642 patients with pDPN) in standard outpatient settings in Germany. These studies evaluated pregabalin for treatment of pDPN. Using these data, we examined "what if" scenarios using a microsimulation platform that integrates data from randomized and observational sources as well as autoregressive-moving-average with exogenous inputs models that predict pain outcomes, taking into account weekly changes in pain, sleep interference, dose, and other patient characteristics that were unchanging. Final pain levels were significantly different depending on dose changes (P titration regardless of baseline pain severity. Altogether, 78.5% of patients with pDPN had 0-1 dose change, and 15.2% had ≥ 2 dose changes. Simulation demonstrated that the 4.8% of inadequately titrated patients who did not improve/very much improve their pain levels would have benefited from ≥ 2 dose changes. Patient satisfaction with tolerability (range 90.3-96.2%) was similar, regardless of baseline pain severity, number of titrations, or extent of improvement, suggesting that tolerability did not influence treatment response patterns. Upward dose titration reduced pain in patients with pDPN who actually received it. Simulation also predicted pain reduction in an inadequately titrated nonresponder subgroup of patients had they actually received adequate titration. The decision not to uptitrate must have been driven by factors other than tolerability. Pfizer, Inc.

  9. An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    William Eardley

    2010-04-01

    Full Text Available William Eardley, Cory TothDepartment of Clinical Neurosciences and the University of Calgary, Calgary, AB, CanadaAbstract: Although many therapies are used in the management of neuropathic pain (NeP due to polyneuropathy (PN, few comparison studies exist. We performed a prospective, non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS pain scores were assessed after 3 and 6 months in intervention groups and in a cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain Inventory [BPI], quality of life and health status measures [EuroQol 5 Domains, EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and Depression Scale [HADS] and Short Form 36 Health Survey [SF-36] after 6 months of therapy. Significant improvements in VAS pain scores occurred for all treatment groups after 6 months. Improvements in aspects of daily life and anxiety were identified in all treatment groups. Our data suggest that monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for NeP management. We advocate for head-to-head, randomized, double-blinded studies of current NeP therapies.Keywords: peripheral neuropathy, neuropathic pain, pharmacotherapy, venlafaxine, gabapentin

  10. Evaluating the Measurement Properties of the Self-Assessment of Treatment Version II, Follow-Up Version, in Patients with Painful Diabetic Peripheral Neuropathy

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    Floortje van Nooten

    2017-01-01

    Full Text Available Background. The Self-Assessment of Treatment version II (SAT II measures treatment-related improvements in pain and impacts and impressions of treatment in neuropathic pain patients. The measure has baseline and follow-up versions. This study assesses the measurement properties of the SAT II. Methods. Data from 369 painful diabetic peripheral neuropathy (PDPN patients from a phase III trial assessing capsaicin 8% patch (Qutenza® efficacy and safety were used in these analyses. Reliability, convergent validity, known-groups validity, and responsiveness (using the Brief Pain Inventory-Diabetic Neuropathy [BPI-DN] and Patient Global Impression of Change [PGIC] analyses were conducted, and minimally important differences (MID were estimated. Results. Exploratory factor analysis supported a one-factor solution for the six impact items. The SAT II has good internal consistency (Cronbach’s alpha: 0.96 and test-retest reliability (intraclass correlation coefficients: 0.62–0.88. Assessment of convergent validity showed moderate to strong correlations with change in other study endpoints. Scores varied significantly by level of pain intensity and sleep interference (p<0.05 defined by the BPI-DN. Responsiveness was shown based on the PGIC. MID estimates ranged from 1.2 to 2.4 (pain improvement and 1.0 to 2.0 (impact scores. Conclusions. The SAT II is a reliable and valid measure for assessing treatment improvement in PDPN patients.

  11. Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.

    Science.gov (United States)

    Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun; Liu, Xian-Guo

    2016-01-01

    Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. © The Author(s) 2016.

  12. Real-life efficacy of pregabalin for the treatment of peripheral neuropathic pain in daily clinical practice in Denmark

    DEFF Research Database (Denmark)

    Crawford, Michael E; Poulsen, Peter Bo; Schiøttz-Christensen, Berit

    2016-01-01

    clinical practice. Compared with baseline, the primary study end points after 3 months of observation were changes in 1) the average level of pain during the past week, 2) the worst level of pain during the past week, and 3) the least level of pain during the past week. The Wilcoxon signed-rank test...

  13. The relationship between numbness, tingling and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA

    NARCIS (Netherlands)

    Wolf, S.L.; Barton, D.L.; Qin, R.; Wos, E.J.; Sloan, J.A.; Liu, H.; Aaronson, N.K.; Satele, D.V.; Mattar, B.I.; Green, N.B.; Loprinzi, C.L.

    2012-01-01

    Background: Chemotherapy-induced peripheral neuropathy (CIPN) is characterized by numbness, tingling, and shooting/burning pain. This analysis was performed to describe the relationship between numbness, tingling, and shooting/burning pain in patients with CIPN, as reported using the EORTC

  14. TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.

    Directory of Open Access Journals (Sweden)

    Nina Boiko

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN, a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1 channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.

  15. Clinical and economic consequences of treating patients with peripheral neuropathic pain with brand name or generic drugs in routine clinical practice: The effects of age and sex.

    Science.gov (United States)

    Navarro-Artieda, R; Rejas-Gutiérrez, J; Pérez-Paramo, M; Sicras-Mainar, A

    2018-04-01

    We aimed to analyse the effects of age and sex on pain and cost for patients with chronic peripheral neuropathic pain (PNP) who have started treatment with brand name gabapentin versus generic gabapentin (EFG). We conducted a retrospective multicentre study using electronic medical records (EMR) for patients of both sexes, older than 18, who began treatment with brand name or generic gabapentin. Adherence (medication possession ratio [MPR]), persistence, use of healthcare resources, cost, and pain reduction were measured for one year. We analysed 1369 EMRs [61.1% women; mean age 64.6 (15.9), 52.4%≥65 years]; 400 used brand name drugs while 969 used generic gabapentin. Persistence and adherence were higher in patients using brand name gabapentin (7.3 vs 6.3 months, Pbrand-name gabapentin in both age groups (brand treatment showed greater pain relief: 13.5% (10.9-16.2) and 10.8% (8.2-13.5) in brand name medication showed greater persistence and adherence to treatment than those taking generic drugs. Brand name treatment also involved lower healthcare costs, and greater pain relief. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Vladimir Skljarevski

    2012-01-01

    Full Text Available We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE study that examine duloxetine 40 and 60 mg once daily (QD in patients with diabetic peripheral neuropathic pain (DPNP. In all placebo-controlled studies, duloxetine showed significantly (P≤.01 greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P≤.05 greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P≤.01 for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P≤.01 between treatment groups in 3 out of 4 studies. The open-label study showed maintenance of analgesic effect of duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients discontinued because of adverse events (placebo groups: 2.6% to 7.4%. Most commonly reported treatment-emergent adverse events were nausea, somnolence, and headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the management of DPNP.

  17. Subcutaneous peripheral nerve stimulation with inter-lead stimulation for axial neck and low back pain: case series and review of the literature.

    Science.gov (United States)

    Burgher, Abram H; Huntoon, Marc A; Turley, Todd W; Doust, Matthew W; Stearns, Lisa J

    2012-01-01

    While pain in the extremities often responds to treatment using spinal cord stimulation (SCS), axial pain is notoriously refractory to SCS. Interest in subcutaneous peripheral nerve stimulation (SQ PNS) as an alternative to SCS has emerged, but the most appropriate electrode locations and neurostimulator programming techniques are not yet clear. A retrospective review was conducted of consecutive patients evaluated from August 2009 to December 2010 who had undergone trial of SQ PNS with inter-lead stimulation for axial spine pain. Patients proceeding to implant were followed postoperatively with routine clinical visits and a survey form at last follow-up. Ultrasound was used intraoperatively to ensure placement of electrodes at the appropriate depth in patients with larger body mass index. Primary outcome was patient-reported pain relief at last follow-up. Literature review was conducted by searching MEDLINE (1948-present) and through an unstructured review by the authors. Ten patients underwent trial of SQ PNS and six proceeded to permanent implantation. Fifty percent (3/6) of implanted patients preferred neurostimulation programming that included inter-lead stimulation ("cross-talk"). Average duration of postoperative follow-up was 4.5 months (range 2-9 months). Average patient-reported pain relief at last follow-up was 45% (range 20-80%). One patient required re-operation for migration. Patients not proceeding to implant had paresthesia coverage but no analgesia. SQ PNS is a promising therapy for axial neck and back pain based on a small cohort of patients. Ultrasound was useful to assist with electrode placement at the most appropriate depth beneath the skin. While inter-lead stimulation has been preferred by patients in published reports, we did not find it clearly influenced pain relief. Future investigations should include a randomized, controlled study design, as well as defined implantation technique and neurostimulator programming algorithms. © 2011

  18. Neuron-Derived ADAM10 Production Stimulates Peripheral Nerve Injury-Induced Neuropathic Pain by Cleavage of E-Cadherin in Satellite Glial Cells.

    Science.gov (United States)

    Li, Jian; Ouyang, Qing; Chen, Cheng-Wen; Chen, Qian-Bo; Li, Xiang-Nan; Xiang, Zheng-Hua; Yuan, Hong-Bin

    2017-09-01

    Increasing evidence suggests the potential involvement of metalloproteinase family proteins in the pathogenesis of neuropathic pain, although the underlying mechanisms remain elusive. Using the spinal nerve ligation model, we investigated whether ADAM10 proteins participate in pain regulation. By implementing invitro methods, we produced a purified culture of satellite glial cells to study the underlying mechanisms of ADAM10 in regulating neuropathic pain. Results showed that the ADAM10 protein was expressed in calcitonin gene-related peptide (CGRP)-containing neurons of the dorsal root ganglia, and expression was upregulated following spinal nerve ligation surgery invivo. Intrathecal administration of GI254023X, an ADAM10 selective inhibitor, to the rats one to three days after spinal nerve ligation surgery attenuated the spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia. Intrathecal injection of ADAM10 recombinant protein simulated pain behavior in normal rats to a similar extent as those treated by spinal nerve ligation surgery. These results raised a question about the relative contribution of ADAM10 in pain regulation. Further results showed that ADAM10 might act by cleaving E-cadherin, which is mainly expressed in satellite glial cells. GI254023X reversed spinal nerve ligation-induced downregulation of E-cadherin and activation of cyclooxygenase 2 after spinal nerve ligation. β-catenin, which creates a complex with E-cadherin in the membranes of satellite glial cells, was also downregulated by spinal nerve ligation surgery in satellite glial cells. Finally, knockdown expression of β-catenin by lentiviral infection in purified satellite glial cells increased expression of inducible nitric oxide synthase and cyclooxygenase 2. Our findings indicate that neuron-derived ADAM10 production stimulates peripheral nerve injury-induced neuropathic pain by cleaving E-cadherin in satellite glial cells. © 2017 American Academy of Pain Medicine

  19. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study

    DEFF Research Database (Denmark)

    Demant, Dyveke T; Lund, Karen; Vollert, Jan

    2014-01-01

    In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo...... patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment....... The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined...

  20. Role of Peripheral Alpha2 Adrenergic Receptors in Tonic Pain During Different Stages of Estrous Cycle in Rats

    OpenAIRE

    AR Abyazi Shelmani; M Taherianfard

    2007-01-01

    Introduction: Estrogen and progesterone are supposed to modify pain sensitivity. However, the actual role of each of these steroid hormones in this respect is not well known. Plasma concentrations of these hormones show variation during estrous cycle. The role of alpha2 receptors in tonic pain has been pointed out. The aim of the present study was to investigate the agonist and antagonist effect of alpha2 adrenergic receptors on tonic pain sensitivity during all stages of estrous cycle in fem...

  1. Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: results from a retrospective chart review and cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Sadosky A

    2013-02-01

    Full Text Available Alesia Sadosky,1 Caroline Schaefer,2 Rachael Mann,3 Felicia Bergstrom,2 Rebecca Baik,2 Bruce Parsons,1 Srinivas Nalamachu,4 Edward Nieshoff,5 Brett R Stacey,6 Alan Anschel,7 Michael Tuchman81Pfizer Inc, New York, NY, 2Covance Market Access Services Inc, Gaithersburg, MD, 3Covance Market Access Services Inc, San Diego, CA, 4International Clinical Research Institute, Overland Park, KS, 5Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, 6Oregon Health and Science University, Portland, OR, 7Rehabilitation Institute of Chicago, Chicago, IL, 8Palm Beach Neurological Center, Palm Beach Gardens, FL, USABackground: The purpose of this study was to characterize the burden of illness among adult subjects with painful diabetic peripheral neuropathy (pDPN seeking treatment in the US.Methods: This observational study recruited 112 subjects with pDPN during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire, which included demographics, symptom duration, health care resource use, out-of-pocket costs, employment status, and validated measures that assessed pain, functioning, sleep, anxiety and depression, health status, and productivity. Investigators completed a case report form based on a 6-month retrospective chart review to capture clinical information, pDPN-related treatments, and other pDPN-related health care resource use over the past 6 months. Annualized costs were extrapolated based on reported 6-month health care resource use.Results: The mean age of the subjects was 61.1 years, 52.7% were female, and 17.9% were in paid employment. The most common comorbid conditions were sleep disturbance/insomnia (43.8%, depressive symptoms (41.1%, and anxiety (35.7%. The mean pain severity score was 5.2 (0–10 scale, and 79.5% reported moderate or severe pain. The mean pain interference with function score was 5.0 (0–10 scale overall, with 2.0 among mild, 5.1 among moderate, and 7

  2. Characteristics, treatment, and health care expenditures of Medicare supplemental-insured patients with painful diabetic peripheral neuropathy, post-herpetic neuralgia, or fibromyalgia.

    Science.gov (United States)

    Johnston, Stephen S; Udall, Margarita; Alvir, Jose; McMorrow, Donna; Fowler, Robert; Mullins, Daniel

    2014-04-01

    To describe the characteristics, treatment, and health care expenditures of Medicare Supplemental-insured patients with painful diabetic peripheral neuropathy (pDPN), post-herpetic neuralgia (PHN), or fibromyalgia. Retrospective cohort study. United States clinical practice, as reflected within a database comprising administrative claims from 2.3 million older adults participating in Medicare supplemental insurance programs. Selected patients were aged ≥65 years, continuously enrolled in medical and prescription benefits throughout years 2008 and 2009, and had ≥1 medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for DPN, PHN, or fibromyalgia, followed within 60 days by a medication or pain intervention procedure used in treating pDPN, PHN, or fibromyalgia during 2008-2009. Utilization of, and expenditures on, pain-related and all-cause pharmacotherapy and medical interventions in 2009. The study included 25,716 patients with pDPN (mean age 75.2 years, 51.2% female), 4,712 patients with PHN (mean age 77.7 years, 63.9% female), and 25,246 patients with fibromyalgia (mean age 74.4 years, 73.0% female). Patients typically had numerous comorbidities, and many were treated with polypharmacy. Mean annual expenditures on total pain-related health care and total all-cause health care, respectively, (in 2010 USD) were: $1,632, $24,740 for pDPN; $1,403, $16,579 for PHN; and $1,635, $18,320 for fibromyalgia. In age-stratified analyses, pain-related health care expenditures decreased as age increased. The numerous comorbidities, polypharmacy, and magnitude of expenditures in this sample of Medicare supplemental-insured patients with pDPN, PHN, or fibromyalgia underscore the complexity and importance of appropriate management of these chronic pain patients. Wiley Periodicals, Inc.

  3. Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: a multicentre, randomized, assessor-blinded study.

    Science.gov (United States)

    Jensen, T S; Høye, K; Fricová, J; Vanelderen, P; Ernault, E; Siciliano, T; Marques, S

    2014-10-01

    Application of the capsaicin 8% patch is associated with treatment-related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream is recommended; however, this may be uncomfortable and time consuming. We conducted a multicentre, randomized (1:1), assessor-blinded study in patients with peripheral neuropathic pain to assess tolerability of the capsaicin patch following topical lidocaine (4%) or oral tramadol (50 mg) pretreatment. The primary endpoint was the proportion of patients tolerating capsaicin patch application (ability to receive ≥90% of a 60-min application). Numeric Pain Rating Scale (NPRS) scores were assessed before, during and after treatment. Overall, 122 patients were included (61 per arm). The capsaicin patch was tolerated by 121 patients. Tolerability of the capsaicin patch was similar following pretreatment with lidocaine and tramadol. Following patch application, pain levels increased up to 55 min (change from baseline of 1.3 for lidocaine and 1.4 for tramadol). After patch removal, tramadol-treated patients experienced greater pain relief up to the end of day 1; in the evening, mean changes in NPRS scores from baseline were 0 for lidocaine and -1 for tramadol. Proportions of patients reporting increases of ≥2 NPRS points or >33% from baseline at one or more time point(s) on the day of treatment were similar between arms. Adverse event incidence was comparable between arms. Capsaicin 8% patch tolerability was similar in the two arms, with comparable results for most secondary endpoints. Tramadol given 30 min before patch application should be considered as an alternative pretreatment option in patients receiving capsaicin patch treatment. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  4. Peripheral Nerve Stimulation of Brachial Plexus Nerve Roots and Supra-Scapular Nerve for Chronic Refractory Neuropathic Pain of the Upper Limb.

    Science.gov (United States)

    Bouche, Bénédicte; Manfiotto, Marie; Rigoard, Philippe; Lemarie, Jean; Dix-Neuf, Véronique; Lanteri-Minet, Michel; Fontaine, Denys

    2017-10-01

    We report the outcome of a consecutive series of 26 patients suffering from chronic medically-refractory neuropathic pain of the upper limb (including 16 patients with complex regional pain syndrome), topographically limited, treated by brachial plexus (BP) nerve roots or supra-scapular nerve (SSN) peripheral nerve stimulation (PNS). The technique consisted in ultrasound-guided percutaneous implantation of a cylindrical lead (Pisces-Quad, Medtronic) close to the SSN or the cervical nerve roots within the BP, depending on the pain topography. All the patients underwent a positive trial stimulation before lead connection to a subcutaneous stimulator. Chronic bipolar stimulation mean parameters were: frequency 55.5 Hertz, voltage 1.17 Volts. The voltage was set below the threshold inducing muscle contractions or paresthesias. Two patients were lost immediately after surgery. At last follow-up (mean 27.5 months), the 20 patients still using the stimulation experienced a mean pain relief of 67.1%. Seventeen patients were improved ≥50%, including 12 improved ≥70%. In 11 patients with a follow-up >2 years, the mean pain relief was 68%. At last follow-up, respectively, six out of the nine (67%) patients treated by SSN stimulation and 10 out of 17 patients (59%) treated by BP stimulation were improved ≥50%. At last follow-up, 12 out of 20 patients still using the stimulation were very satisfied, six were satisfied, and two were poorly satisfied. Complications were: stimulation intolerance due to shock-like sensations (three cases), superficial infection (1), lead fractures (2), and migration (1). In this pilot study, SSN or BP roots PNS provided a relatively safe, durable and effective option to control upper limb neuropathic pain. © 2017 International Neuromodulation Society.

  5. Effects of low-dose IV ketamine on peripheral and central pain from major limb injuries sustained in combat.

    Science.gov (United States)

    Polomano, Rosemary C; Buckenmaier, Chester C; Kwon, Kyung H; Hanlon, Alexandra L; Rupprecht, Christine; Goldberg, Cynthia; Gallagher, Rollin M

    2013-07-01

    Examine response patterns to low-dose intravenous (IV) ketamine continuous infusions on multiple pain outcomes, and demonstrate effectiveness, safety, and tolerability of ketamine administration on general wards. Retrospective case series of consecutive patients given low-dose IV ketamine continuous infusions. Walter Reed Army Medical Center, Washington, DC. Nineteen eligible inpatients with neuropathic pain from major limb injuries sustained in combat with inadequate pain control from multimodal analgesia. A 3-day IV infusion of ketamine at doses ≤ 120 μg/kg/h. Daily present (PPI), average (API), and worst (WPI) pain intensity (0-10), global pain relief (GPR) (1 "no relief" to 5 "complete relief"), daily assessments of adverse events, and daily opioid requirements measured during therapy. A significant reduction in PPI (P pain (PLP) (N = 10; P = 0.0436) were observed. Mean percent increase in overall GPR was better for those reporting GPR scores ≤ 3 (N = 13) in the first 24 hours of therapy (P = 0.0153). While not significant, mean opioid requirement (IV morphine equivalents) decreased from 129.9 mgs ± 137.3 on day 1 to 112.14 ± 86.3 24 hours after therapy. Low-dose ketamine infusions for complex combat injury pain were safe and effective, and demonstrated response patterns over time and by baseline pain score stratification and presence or absence of PLP. Wiley Periodicals, Inc.

  6. Percutaneous Augmented Peripheral Osteoplasty in Long Bones of Oncologic Patients for Pain Reduction and Prevention of Impeding Pathologic Fracture: The Rebar Concept

    International Nuclear Information System (INIS)

    Kelekis, A.; Filippiadis, D.; Anselmetti, G.; Brountzos, E.; Mavrogenis, A.; Papagelopoulos, P.; Kelekis, N.; Martin, J.-B.

    2016-01-01

    PurposeTo evaluate clinical efficacy/safety of augmented peripheral osteoplasty in oncologic patients with long-term follow-up.Materials and MethodsPercutaneous augmented peripheral osteoplasty was performed in 12 patients suffering from symptomatic lesions of long bones. Under extensive local sterility measures, anesthesiology care, and fluoroscopic guidance, direct access to lesion was obtained and coaxially a metallic mesh consisting of 25–50 medical grade stainless steel micro-needles (22 G, 2–6 cm length) was inserted. PMMA for vertebroplasty was finally injected under fluoroscopic control. CT assessed implant position 24-h post-treatment.ResultsClinical evaluation included immediate and delayed follow-up studies of patient’s general condition, NVS pain score, and neurological status. Imaging assessed implant’s long-term stability. Mean follow-up was 16.17 ± 10.93 months (range 2–36 months). Comparing patients’ scores prior (8.33 ± 1.67 NVS units) and post (1.42 ± 1.62 NVS units) augmented peripheral osteoplasty, there was a mean decrease of 6.92 ± 1.51 NVS units. Overall mobility improved in 12/12 patients. No complication was observed.ConclusionPercutaneous augmented peripheral osteoplasty (rebar concept) for symptomatic malignant lesions in long bones seems to be a possible new technique for bone stabilization. This combination seems to provide necessary stability against shearing forces applied in long bones during weight bearing

  7. Percutaneous Augmented Peripheral Osteoplasty in Long Bones of Oncologic Patients for Pain Reduction and Prevention of Impeding Pathologic Fracture: The Rebar Concept

    Energy Technology Data Exchange (ETDEWEB)

    Kelekis, A., E-mail: akelekis@med.uoa.gr; Filippiadis, D., E-mail: dfilippiadis@yahoo.gr [University General Hospital “ATTIKON”, 2nd Radiology Department (Greece); Anselmetti, G., E-mail: gc.anselmetti@fastwebnet.it [GVM Care and Research Maria Pia Hospital (Italy); Brountzos, E., E-mail: ebrountz@med.uoa.gr [University General Hospital “ATTIKON”, 2nd Radiology Department (Greece); Mavrogenis, A., E-mail: afm@otenet.gr; Papagelopoulos, P., E-mail: pjp@hol.gr [University General Hospital “ATTIKON”, A Orthopedic Clinic (Greece); Kelekis, N., E-mail: kelnik@med.uoa.gr [University General Hospital “ATTIKON”, 2nd Radiology Department (Greece); Martin, J.-B., E-mail: jbmartin@cird.ch [Centre Imaginerie Rive Droite & Gauche (Switzerland)

    2016-01-15

    PurposeTo evaluate clinical efficacy/safety of augmented peripheral osteoplasty in oncologic patients with long-term follow-up.Materials and MethodsPercutaneous augmented peripheral osteoplasty was performed in 12 patients suffering from symptomatic lesions of long bones. Under extensive local sterility measures, anesthesiology care, and fluoroscopic guidance, direct access to lesion was obtained and coaxially a metallic mesh consisting of 25–50 medical grade stainless steel micro-needles (22 G, 2–6 cm length) was inserted. PMMA for vertebroplasty was finally injected under fluoroscopic control. CT assessed implant position 24-h post-treatment.ResultsClinical evaluation included immediate and delayed follow-up studies of patient’s general condition, NVS pain score, and neurological status. Imaging assessed implant’s long-term stability. Mean follow-up was 16.17 ± 10.93 months (range 2–36 months). Comparing patients’ scores prior (8.33 ± 1.67 NVS units) and post (1.42 ± 1.62 NVS units) augmented peripheral osteoplasty, there was a mean decrease of 6.92 ± 1.51 NVS units. Overall mobility improved in 12/12 patients. No complication was observed.ConclusionPercutaneous augmented peripheral osteoplasty (rebar concept) for symptomatic malignant lesions in long bones seems to be a possible new technique for bone stabilization. This combination seems to provide necessary stability against shearing forces applied in long bones during weight bearing.

  8. 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.

  9. Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls – a hypothesis-generating pilot study

    Directory of Open Access Journals (Sweden)

    Bäckryd E

    2015-07-01

    Full Text Available Emmanuel Bäckryd,1,2 Bijar Ghafouri,1,2 Anders K Carlsson,1,2 Patrik Olausson,1,2 Björn Gerdle1,2 1Division of Community Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden; 2Pain and Rehabilitation Centre, Anaesthetics, Operations and Specialty Surgery Centre, Region Östergötland, Linköping, SwedenAbstract: Pain medicine lacks objective biomarkers to guide diagnosis and treatment. Combining two-dimensional gel proteomics with multivariate data analysis by projection, we exploratively analyzed the cerebrospinal fluid of eleven patients with severe peripheral neuropathic pain due to trauma and/or surgery refractory to conventional treatment and eleven healthy controls. Using orthogonal partial least squares discriminant analysis, we identified a panel of 36 proteins highly discriminating between the two groups. Due to a possible confounding effect of age, a new model with age as outcome variable was computed for patients (n=11, and four out of 36 protein spots were excluded due to a probable influence of age. Of the 32 remaining proteins, the following seven had the highest discriminatory power between the two groups: an isoform of angiotensinogen (upregulated in patients, two isoforms of alpha-1-antitrypsin (downregulated in patients, three isoforms of haptoglobin (upregulated in patients, and one isoform of pigment epithelium-derived factor (downregulated in patients. It has recently been hypothesized that the renin–angiotensin system may play a role in the pathophysiology of neuropathic pain, and a clinical trial of an angiotensin II receptor antagonist was recently published. It is noteworthy that when searching for neuropathic pain biomarkers with a purely explorative methodology, it was indeed a renin–angiotensin system protein that had the highest discriminatory power between patients and controls in the present study. The results from this hypothesis

  10. How effective is tetracaine 4% gel, before a peripherally inserted central catheter, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial [ISRCTN75884221

    Directory of Open Access Journals (Sweden)

    Blanchard Colline

    2006-05-01

    Full Text Available Abstract Background Procedural pain relief is sub-optimal in infants, especially small and vulnerable ones. Tetracaine gel 4% (Ametop®, Smith-Nephew provides pain relief in children and larger infants, but its efficacy in smaller infants and for peripherally inserted central catheters (PICC remains uncertain. The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight (VLBW infants during insertion of a PICC. Methods Medically stable infants greater than or equal to 24 weeks gestation, requiring a non-urgent PICC, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. The PICC was inserted according to a standard protocol. Pain was assessed using the Premature Infant Pain Profile (PIPP. A 3-point change in the pain score was considered clinically significant, leading to a sample size of 54 infants, with 90% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. Results Fifty-four infants were included, 27 +/- 2 weeks gestation, 916 +/- 292 grams and 6.5 +/- 3.2 days of age. Baseline characteristics were similar between groups. The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group (difference 0.86, 95% CI -1.86, 3.58. Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group (difference -78, 95% CI -539, 117. Local skin erythema was observed transiently in 4 infants (3 in the treatment and 1 in the placebo group. No serious harms were observed. Conclusion Tetracaine 4% when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants.

  11. Integrating data from randomized controlled trials and observational studies to predict the response to pregabalin in patients with painful diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Joe Alexander

    2017-07-01

    Full Text Available Abstract Background More patient-specific medical care is expected as more is learned about variations in patient responses to medical treatments. Analytical tools enable insights by linking treatment responses from different types of studies, such as randomized controlled trials (RCTs and observational studies. Given the importance of evidence from both types of studies, our goal was to integrate these types of data into a single predictive platform to help predict response to pregabalin in individual patients with painful diabetic peripheral neuropathy (pDPN. Methods We utilized three pivotal RCTs of pregabalin (398 North American patients and the largest observational study of pregabalin (3159 German patients. We implemented a hierarchical cluster analysis to identify patient clusters in the Observational Study to which RCT patients could be matched using the coarsened exact matching (CEM technique, thereby creating a matched dataset. We then developed autoregressive moving average models (ARMAXs to estimate weekly pain scores for pregabalin-treated patients in each cluster in the matched dataset using the maximum likelihood method. Finally, we validated ARMAX models using Observational Study patients who had not matched with RCT patients, using t tests between observed and predicted pain scores. Results Cluster analysis yielded six clusters (287–777 patients each with the following clustering variables: gender, age, pDPN duration, body mass index, depression history, pregabalin monotherapy, prior gabapentin use, baseline pain score, and baseline sleep interference. CEM yielded 1528 unique patients in the matched dataset. The reduction in global imbalance scores for the clusters after adding the RCT patients (ranging from 6 to 63% depending on the cluster demonstrated that the process reduced the bias of covariates in five of the six clusters. ARMAX models of pain score performed well (R 2 : 0.85–0.91; root mean square errors: 0.53–0

  12. The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms.

    Science.gov (United States)

    Alsalem, Mohammad; Wong, Amy; Millns, Paul; Arya, Pallavi Huma; Chan, Michael Siang Liang; Bennett, Andrew; Barrett, David A; Chapman, Victoria; Kendall, David A

    2013-04-01

    The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9- and 13- hydroxyoctadecadienoic acid (HODE)] to TRPV1-mediated noxious responses and inflammatory pain responses. 9- and 13-HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan-inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9-HODE- and 13-HODE-evoked responses, and the contribution of 15-lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9- and 13-HODE and 15-lipoxygenase to inflammatory pain behaviour. 9-HODE (35 ± 7 pmol g(-1)) and 13-HODE (32 ± 6 pmol g(-1)) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9- and 13-HODE were detected in DRGs and TRPV1 antagonist-sensitive calcium responses evoked, which were blocked by the 15-lipoxygenase inhibitor PD146176 and an anti-13-HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan-inflamed hindpaw (P PD146176 significantly (P < 0.01) attenuated carrageenan-induced hyperalgesia. This study demonstrates that, although 9- and 13-HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  13. Patellar and Achilles tendinopathies are predominantly peripheral pain states : a blinded case control study of somatosensory and psychological profiles

    NARCIS (Netherlands)

    Plinsinga, Melanie L; van Wilgen, Cornelis P; Brink, Michel S; Vuvan, Viana; Stephenson, Aoife; Heales, Luke J; Mellor, Rebecca; Coombes, Brooke K; Vicenzino, Bill T

    Study design Case-control design. Background Tendinopathy is characterised by pain on tendon loading. In persistent cases of upper limb tendinopathy, it is frequently associated with central nervous system sensitisation, whereas less commonly linked in the case of persistent lower limb

  14. Role of Peripheral Alpha2 Adrenergic Receptors in Tonic Pain During Different Stages of Estrous Cycle in Rats

    Directory of Open Access Journals (Sweden)

    AR Abyazi Shelmani

    2007-12-01

    Full Text Available Introduction: Estrogen and progesterone are supposed to modify pain sensitivity. However, the actual role of each of these steroid hormones in this respect is not well known. Plasma concentrations of these hormones show variation during estrous cycle. The role of alpha2 receptors in tonic pain has been pointed out. The aim of the present study was to investigate the agonist and antagonist effect of alpha2 adrenergic receptors on tonic pain sensitivity during all stages of estrous cycle in female rats. Methods: Xylasine as alpha2 agonist and yohimbin as alpha2 antagonist were used via intraperitoneal route (IP. Adult rats weighing 180-200 grams were used. Animals were maintained on 12h reverse light/dark cycle for 7 days prior to the experiment. Water and food was available ad libitum. Formalin test was performed by subcutaneous injection of 50 l formalin (2.5% solution into the hind paw. Formalin test was performed in all stages of estrous cycle for 60 minutes. Animals were divided into four groups; 1- control group (intact animal, 2- Sham group (animals received 0.2 ml normal saline by IP route, 3- Agonist groups (animals received 0.2 ml xylasine 1, 3 mg/kg body weight by IP route and 4- Antagonist group (animals received 0.2 ml yohimbine 1, 3 mg/kg body weight by IP route. Data were statistically analyzed using 2 way ANOVA test followed by Tukey's test as post-hoc test. P<0.05 was considered significant. Results: Results showed that xylasine significantly (p<0.05 decreases pain sensitivity in all stages of estrous cycle. Analgesic effect of xylasine was maximum in estrus stage of estrous cycle and minimum in metestrus stage of estrous cycle. Yohimbine significantly (p<0.05 increases pain sensitivity in all stages of estrous cycle. Hyperalgesic effect of yohimbine was maximum in metestrus stage of estrous cycle and minimum in estrus stage of estrous cycle. Conclusion: These results indicate that alpha2 adrenergic system and endogenous

  15. Duloxetine for the management of diabetic peripheral neuropathic pain: evidence-based findings from post hoc analysis of three multicenter, randomized, double-blind, placebo-controlled, parallel-group studies

    DEFF Research Database (Denmark)

    Kajdasz, Daniel K; Iyengar, Smriti; Desaiah, Durisala

    2007-01-01

    peripheral neuropathic pain (DPNP). METHODS: Data were pooled from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in which patients received 60 mg duloxetine either QD or BID or placebo. NNT was calculated based on rates of response (defined as >or=30...

  16. Participation of peripheral TRPV1, TRPV4, TRPA1 and ASIC in a magnesium sulfate-induced local pain model in rat.

    Science.gov (United States)

    Srebro, Dragana; Vučković, Sonja; Prostran, Milica

    2016-12-17

    We previously showed that magnesium sulfate (MS) has systemic antinociceptive and local peripheral pronociceptive effects. The role of transient receptor potential (TRP) channels and acid-sensing ion channels (ASICs) in the mechanism of action of MS has not been investigated in detail. The aim of this study was to explore the participation of TRP channels in the pronociceptive action of MS in rats after its intraplantar injection. The paw withdrawal threshold (PWT) to mechanical stimuli was measured by the electronic von Frey test. Drugs that were tested were either co-administered with an isotonic pH-unadjusted or pH-adjusted solution of MS intraplantarily, or to the contralateral paw to exclude systemic effects. We found that the subcutaneous administration of both pH-adjusted (7.4) and pH-unadjusted (about 6.0) isotonic (6.2% w/v in water) solutions of MS induce the pain at the injection site. The pH-unadjusted MS solution-induced mechanical hyperalgesia decreased in a dose-dependent manner as a consequence of co-injection of capsazepine, a selective TRPV1 antagonist (20, 100 and 500pmol/paw), RN-1734, a selective TRPV4 antagonist (1.55, 3.1 and 6.2μmol/paw), HC-030031, a selective TRPA1 antagonist (5.6, 28.1 and 140nmol/paw), and amiloride hydrochloride, a non-selective ASIC inhibitor (0.83, 2.5 and 7.55μmol/paw). In pH-adjusted MS-induced hyperalgesia, the highest doses of TRPV1, TRPV4 and TRPA1 antagonists displayed effects that were, respectively, either similar, less pronounced or delayed in comparison to the effect induced by administration of the pH-unadjusted MS solution; the ASIC antagonist did not have any effect. These results suggest that the MS-induced local peripheral mechanical hyperalgesia is mediated via modulation of the activity of peripheral TRPV1, TRPV4, TRPA1 and ASICs. Specific local inhibition of TRP channels represents a novel approach to treating local injection-related pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All

  17. Wireless peripheral nerve stimulation for complex regional pain syndrome type I of the upper extremity: a case illustration introducing a novel technology.

    Science.gov (United States)

    Herschkowitz, Daniel; Kubias, Jana

    2018-04-13

    Complex regional pain syndrome (CRPS) is a debilitating painful disorder, cryptic in its pathophysiology and refractory condition with limited therapeutic options. Type I CRPS with its variable relationship to trauma has often no discernible fractures or nerve injuries and remains enigmatic in its response to conservative treatment as well as the other limited interventional therapies. Neuromodulation in the form of spinal cord and dorsal root ganglion stimulation (SCS, DRGS) has shown encouraging results, especially of causalgia or CRPS I of lower extremities. Upper extremity CRPS I is far more difficult. To report a case of upper extremity CRPS I treated by wireless peripheral nerve stimulation (WPNS) for its unique features and minimally invasive technique. The system does not involve implantation of battery or its connections. A 47 year old female patient presented with refractory CRPS I following a blunt trauma to her right forearm. As interventional treatment in the form of local anesthetics (Anesthesia of peripheral branches of radial nerve) and combined infusions of ketamine/lidocaine failed to provide any significant relief she opted for WPNS treatment. Based on the topographic distribution, two electrodes (Stimwave Leads: FR4A-RCV-A0 with tines, Generation 1 and FR4A-RCV-B0 with tines, Generation 1), were placed along the course of radial and median nerves under ultrasonography monitoring and guided by intraoperative stimulation. This procedure did not involve implantation of extension cables or the power source. At a frequency of 60 Hz and 300 μs the stimulation induced paresthesia along the distribution of the nerves. Therapeutic relief was observed with high frequency (HF) stimulation (HF 10 kHz/32 μs, 2.0 mA) reducing her pain from a visual analogue scale (VAS) score of 7-4 postoperatively. Three HF stimulations programs were provided at the time of discharge, as she improved in her sensory impairment to touch, pressure and temperature at her first

  18. Pain

    OpenAIRE

    H.W. Snyman

    1980-01-01

    The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  19. Pain

    Directory of Open Access Journals (Sweden)

    H.W. Snyman

    1980-09-01

    Full Text Available The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  20. The McKenzie method compared with manipulation when used adjunctive to information and advice in low back pain patients presenting with centralization or peripheralization. A randomized controlled trial

    DEFF Research Database (Denmark)

    Petersen, Tom; Larsen, Kristian; Nordsteen, Jan

    2011-01-01

    .Methods. A total of 350 patients suffering from low back pain with a duration of more than 6 weeks who presented with centralization or peripheralization of symptoms with or without signs of nerve root involvement, were enrolled in the trial. Main outcome was number of patients with treatment success defined...... a structured exercise programme tailored to the individual patient as well as manual therapy for the treatment of persistent low back pain. There is presently insufficient evidence to recommend the use of specific decision methods tailoring specific therapies to clinical subgroups of patients in primary care...... for more than six weeks presenting with centralization or peripheralization of symptoms, we found the McKenzie method to be slightly more effective than manipulation when used adjunctive to information and advice....

  1. Karolinska institutet 200-year anniversary. Symposium on traumatic injuries in the nervous system: injuries to the spinal cord and peripheral nervous system - injuries and repair, pain problems, lesions to brachial plexus.

    Science.gov (United States)

    Sköld, Mattias K; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

    2011-01-01

    The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented.

  2. Karolinska Institutet 200-Year Anniversary. Symposium on Traumatic Injuries in the Nervous System: Injuries to the Spinal Cord and Peripheral Nervous System – Injuries and Repair, Pain Problems, Lesions to Brachial Plexus

    Science.gov (United States)

    Sköld, Mattias K.; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

    2011-01-01

    The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented. PMID:21629875

  3. Duloxetine in the long-term management of diabetic peripheral neuropathic pain: An open-label, 52-week extension of a randomized controlled clinical trial.

    Science.gov (United States)

    Wernicke, Joachim F; Raskin, Joel; Rosen, Amy; Pritchett, Yili L; D'Souza, Deborah N; Iyengar, Smriti; Knopp, Kelly; Le, Trong K

    2006-09-01

    Duloxetine hydrochloride, a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor, is relatively balanced in its affinity for both 5-HT and NE reuptake inhibition and is the first US Food and Drug Administration-approved prescription drug for the management of diabetic peripheral neuropathic pain (DPNP). The aim of this study was to determine whether management of DPNP with duloxetine interferes with the treatment of diabetes. It also examined the tolerability of long-term exposure to duloxetine with regard to the progression of diabetic complications, and assessed the impact of DPNP management with duloxetine versus routine care. This was a 52-week, multicenter, re-randomized, open-label extension of a parallel, double-blind, randomized, placebo-controlled, acute (12-week) study. Patients who completed the duloxetine or placebo acute treatment period were randomly reassigned in a 2:1 ratio to treatment with duloxetine 60 mg BID or routine care for an additional 52 weeks. The study included male and female outpatients aged ≥18 years with a diagnosis of DPNP caused by type 1 or type 2 diabetes. Over the course of the 52-week study, visits were scheduled on the following weeks (of the extension phase of the study): 1 (via phone only), 2, 4, 8, 12, 20, 28, 40, and 52. Tolerability was assessed by review and analyses of discontinuation rates, adverse events (AEs), laboratory data, vital signs, electrocardiographic results, concomitant medications, and diabetic complications. Treatment-emergent AEs (TEAEs) were defined as AEs that appeared during therapy (were not present at baseline) or were exacerbated during treatment. Data on AEs and concomitant medications were collected at every visit. Data on blood pressure, heart rate, and significant hypoglycemic events were collected at every visit starting from week 2. Fasting clinical chemistry and electrolyte group laboratory assessments were done at every visit, starting from week 4. Electrocardiographic

  4. 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.

  5. Is there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes?

    DEFF Research Database (Denmark)

    Hestehave, Sara; Munro, Gordon; Christensen, Rie

    2017-01-01

    INTRODUCTION: The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment. However...

  6. 21. Phantom pain.

    NARCIS (Netherlands)

    Wolff, A.P.; Vanduynhoven, E.; Kleef, M. van; Huygen, F.; Pope, J.E.; Mekhail, N.

    2011-01-01

    Phantom pain is pain caused by elimination or interruption of sensory nerve impulses by destroying or injuring the sensory nerve fibers after amputation or deafferentation. The reported incidence of phantom limb pain after trauma, injury or peripheral vascular diseases is 60% to 80%. Over half the

  7. Pain: Hope through Research

    Science.gov (United States)

    ... in drugstores. Chiropractic care may ease back pain, neck pain, headaches, and musculoskeletal conditions. It involves "hands-on" ... together. The peripheral nervous system refers to the cervical, thoracic, ... or dysfunction (such as pain) travel from the brain to the spinal cord ...

  8. Spinal pain

    International Nuclear Information System (INIS)

    Izzo, R.; Popolizio, T.; D’Aprile, P.; Muto, M.

    2015-01-01

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  9. Spinal pain

    Energy Technology Data Exchange (ETDEWEB)

    Izzo, R., E-mail: roberto1766@interfree.it [Neuroradiology Department, A. Cardarelli Hospital, Naples (Italy); Popolizio, T., E-mail: t.popolizio1@gmail.com [Radiology Department, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (Fg) (Italy); D’Aprile, P., E-mail: paoladaprile@yahoo.it [Neuroradiology Department, San Paolo Hospital, Bari (Italy); Muto, M., E-mail: mutomar@tiscali.it [Neuroradiology Department, A. Cardarelli Hospital, Napoli (Italy)

    2015-05-15

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  10. The Management of Myofascial Pain Syndrome

    African Journals Online (AJOL)

    QuickSilver

    pain syndrome (MFPS) was attributed to an inflammation of fibrous tissue ... Afferent nerve fibres to muscle are classified as groups I, II,. III and IV. .... tion of pain. There is evidence that pain caused by peripheral .... C. Occupational therapy.

  11. The Appropriate Use of Neurostimulation of the Spinal Cord and Peripheral Nervous System for the Treatment of Chronic Pain and Ischemic Diseases : The Neuromodulation Appropriateness Consensus Committee

    NARCIS (Netherlands)

    Deer, Timothy R.; Mekhail, Nagy; Provenzano, David; Pope, Jason; Krames, Elliot; Leong, Michael; Levy, Robert M.; Abejon, David; Buchser, Eric; Burton, Allen; Buvanendran, Asokumar; Candido, Kenneth; Caraway, David; Cousins, Michael; de Jongste, Micheal; Diwan, Sudhir; Eldabe, Sam; Gatzinsky, Kliment; Foreman, Robert D.; Hayek, Salim; Kim, Philip; Kinfe, Thomas; Kloth, David; Kumar, Krishna; Rizvi, Syed; Lad, Shivanand P.; Liem, Liong; Linderoth, Bengt; Mackey, Sean; McDowell, Gladstone; McRoberts, Porter; Poree, Lawrence; Prager, Joshua; Raso, Lou; Rauck, Richard; Russo, Marc; Simpson, Brian; Slavin, Konstantin; Staats, Peter; Stanton-Hicks, Michael; Verrills, Paul; Wellington, Joshua; Williams, Kayode; North, Richard

    Introduction: The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended

  12. Peripheral reactions

    International Nuclear Information System (INIS)

    Greiner, D.

    1978-01-01

    Peripheral collisions, that is, collisions involving a small amount of overlap of nuclear matter, are discussed including inclusive interactions, the magnitude of the peripheral cross section, fragmentation, a compilation of experiments and available data, limiting fragmentation, factorization, some models, fragment momentum distributions, and future research directions

  13. Effect of cervical vs. thoracic spinal manipulation on peripheral neural features and grip strength in subjects with chronic mechanical neck pain: a randomized controlled trial.

    Science.gov (United States)

    Bautista-Aguirre, Francisco; Oliva-Pascual-Vaca, Ángel; Heredia-Rizo, Alberto M; Boscá-Gandía, Juan J; Ricard, François; Rodriguez-Blanco, Cleofás

    2017-06-01

    Cervical and thoracic spinal manipulative therapy has shown positive impact for relief of pain and improve function in non-specific mechanical neck pain. Several attempts have been made to compare their effectiveness although previous studies lacked a control group, assessed acute neck pain or combined thrust and non-thrust techniques. To compare the immediate effects of cervical and thoracic spinal thrust manipulations on mechanosensitivity of upper limb nerve trunks and grip strength in patients with chronic non-specific mechanical neck pain. Randomized, single-blinded, controlled clinical trial. Private physiotherapy clinical consultancy. Eighty-eight subjects (32.09±6.05 years; 72.7% females) suffering neck pain (grades I or II) of at least 12 weeks of duration. Participants were distributed into three groups: 1) cervical group (N.=28); 2) thoracic group (N.=30); and 3) control group (N.=30). One treatment session consisting of applying a high-velocity low-amplitude spinal thrust technique over the lower cervical spine (C7) or the upper thoracic spine (T3) was performed, while the control group received a sham-manual contact. Measurements were taken at baseline and after intervention of the pressure pain threshold over the median, ulnar and radial nerves. Secondary measures included assessing free-pain grip strength with a hydraulic dynamometer. No statistically significant differences were observed when comparing between-groups in any of the outcome measures (P>0.05). Those who received thrust techniques, regardless of the manipulated area, reported an immediate increase in mechanosensitivity over the radial (both sides) and left ulnar nerve trunks (Ppain perception over the radial nerve also improved (P≤0.025). Low-cervical and upper-thoracic thrust manipulation is no more effective than placebo to induce immediate changes on mechanosensitivity of upper limb nerve trunks and grip strength in patients with chronic non-specific mechanical neck pain. A single

  14. [Morphological substrate and pathogenetic mechanisms of pelvic pain syndrome in endometriosis. Part II. Peripheral nerve tissue remodeling in the foci of endometriosis].

    Science.gov (United States)

    Kogan, E A; Ovakimyan, A S; Paramonova, N B; Faizullina, N M; Kazachenko, I F; Adamyan, L V

    2016-01-01

    Endometriosis (EM) is morphologically characterized by the development of extrauterine endometrioid heterotopies, the major clinical symptoms of which is chronic pelvic pain, which is a serious problem not only in modern gynecology, but also in public health as a whole. to investigate neurogenic markers in the foci of EM of various sites and histological structure in women with and without pain syndrome. The investigation was performed using the operative material (resected segments of the intestine, bladder, rectovaginal septum, and small pelvic peritoneum) obtained from 52 women with an intraoperative and morphologically verified diagnosis of EM and (Group 1) and without (Group 2) pain syndrome. Immunohistochemical examination was made on paraffin-embedded tissue sections in accordance with the standard protocols, by using the antibodies: 1) anti-PGP 9.5 polyclonal rabbit antibodies; 2) mouse anti-human neurofilament (NF) protein monoclonal antibodies (Clone 2F1); 3) mouse anti-nerve growth factor (NGF) monoclonal antibodies; 4) monoclonal mouse anti-human NGF receptor p75 (NGFRp75) antibodies (Dako, Denmark). Our findings demonstrate differences in the expression of PGP 9.5, NFs, NGF, and NGFRp75 in the foci and adjacent tissue in painful and painless EM irrespective of the locations of heterotopies. The found molecular features are a manifestation of the remodeling of nerve fibers and nerve endings in the foci of EM and PGP9.5, NGF, and NGFRp75 give rise to nerve fiber neoformation and pain syndrome in EM. At the same time, the immunohistochemical phenotype of EM foci does not depend on their site and reflects the presence or absence of pain syndrome.

  15. Peripheral dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Sushant S Kamat

    2013-01-01

    Full Text Available Dentinogenic ghost cell tumors (DGCT are uncommon lesions mainly with rare peripheral types. This report presents a case of peripheral DGCT on the left side of the mandibular alveolar ridge of a heavy smoker, a 68-year-old man, with main presenting feature as a mild pain. Submandibular lymphadenopathy and radiological "saucerization" were evident. Differential diagnosis included fibroma, neurofibroma, peripheral ameloblastoma, peripheral odontogenic fibroma, and peripheral giant cell granuloma. Histologically, ameloblastoma-like epithelial elements were seen in association with grouped ghost cells. Proliferating polyhedral cells and stellate reticulum-like cells with various densities were spread over a wide range of the field. The lesion was curetted and after 2 years of follow up, it did not recur.

  16. Is there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes?

    Directory of Open Access Journals (Sweden)

    Sara Hestehave

    Full Text Available The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment. However, a large number of researchers avoid providing such care based largely on anecdotal opinions that it might interfere with model pathophysiology in the longer term.To investigate effects of various peri-operative analgesic regimens encapsulating different mechanisms and duration of action, on the development of post-operative stress/welfare and pain-like behaviors in the Spared Nerve Injury (SNI-model of neuropathic pain.Starting on the day of surgery, male Sprague-Dawley rats were administered either vehicle (s.c., carprofen (5.0mg/kg, s.c., buprenorphine (0.1mg/kg s.c. or 1.0mg/kg p.o. in Nutella®, lidocaine/bupivacaine mixture (local irrigation or a combination of all analgesics, with coverage from a single administration, and up to 72 hours. Post-operative stress and recovery were assessed using welfare parameters, bodyweight, food-consumption, and fecal corticosterone, and hindpaw mechanical allodynia was tested for assessing development of neuropathic pain for 28 days.None of the analgesic regimes compromised the development of mechanical allodynia. Unexpectedly, the combined treatment with 0.1mg/kg s.c. buprenorphine and carprofen for 72 hours and local irrigation with lidocaine/bupivacaine, caused severe adverse effects with peritonitis. This was not observed when the combination included a lower dose of buprenorphine (0.05mg/kg, s.c., or when buprenorphine was administered alone (0.1mg/kg s.c. or 1.0mg/kg p.o. for 72 hours. An elevated rate of wound dehiscence was observed especially in the combined treatment groups, underlining the need for balanced analgesia. Repeated buprenorphine injections had positive effects on body weight the first day after surgery

  17. Altered Pain Sensitivity in Elderly Women with Chronic Neck Pain

    Science.gov (United States)

    Uthaikhup, Sureeporn; Prasert, Romchat; Paungmali, Aatit; Boontha, Kritsana

    2015-01-01

    Background Age-related changes occur in both the peripheral and central nervous system, yet little is known about the influence of chronic pain on pain sensitivity in older persons. The aim of this study was to investigate pain sensitivity in elders with chronic neck pain compared to healthy elders. Methods Thirty elderly women with chronic neck pain and 30 controls were recruited. Measures of pain sensitivity included pressure pain thresholds, heat/cold pain thresholds and suprathreshold heat pain responses. The pain measures were assessed over the cervical spine and at a remote site, the tibialis anterior muscle. Results Elders with chronic neck pain had lower pressure pain threshold over the articular pillar of C5-C6 and decreased cold pain thresholds over the cervical spine and tibialis anterior muscle when compared with controls (p pain thresholds and suprathreshold heat pain responses (p > 0.05). Conclusion The presence of pain hypersensitivity in elderly women with chronic neck pain appears to be dependent on types of painful stimuli. This may reflect changes in the peripheral and central nervous system with age. PMID:26039149

  18. Peripheral vascular response to mild indirect cooling in patients with homozygous sickle cell (SS) disease and the frequency of painful crisis.

    Science.gov (United States)

    Mohan, J; Marshall, J M; Reid, H L; Thomas, P W; Hambleton, I; Serjeant, G R

    1998-02-01

    1. In homozygous sickle cell (SS) disease, skin cooling is a common precipitating factor of the painful crisis which is associated with avascular necrosis of active bone marrow. Since skin cooling does not directly induce sickling, we have investigated the nature of the reflex vascular responses to mild cooling in SS patients in a steady state of the disease and compared them with their history of painful crises. 2. Experiments were performed in Jamaica on 60 male SS patients and 30 matched control subjects with normal haemoglobin (AA) genotype. Forearm blood flow (FBF) was measured by venous occlusion plethysmography and mean arterial pressure (MAP) by a Finapres device: forearm vascular resistance (FVR) was calculated as MAP/FBF. Cutaneous erythrocyte flux in forearm and hand was monitored by a laser Doppler meter. The contralateral hand was immersed in cool water at 16 degrees C for 2 min, 6 times, at random intervals of 0.5-3 min. 3. The first cool immersion evoked an increase in MAP, cutaneous vasoconstriction and a net increase in FVR in both AA and SS subjects. However, the direction of change in FVR varied between individuals such that 18 AA subjects showed an increase in FVR (constrictor group) while 12 showed a decrease in FVR, indicating vasodilatation in forearm muscle (dilator group). In contrast, 50 SS subjects showed an increase in FVR and only 10 showed a decrease in FVR. The proportion of subjects who showed net vasoconstriction was significantly greater in the SS than in the AA group (83% versus 60%, P = 0.03, chi 2 test). 4. By the sixth cool stimulus, the 'dilator' group of AA subjects showed no change in FVR while the 'dilator' group of SS patients showed an increase in FVR. We suggest that forearm muscle vasodilatation was the characteristic component of the alerting/defence response to novel or noxious stimuli which habituates on repetition. 5. In the whole group of SS patients, baseline values of cutaneous vascular resistance and FVR

  19. Peripheral degenerative joint diseases

    Directory of Open Access Journals (Sweden)

    Nilzio Antonio da Silva

    2008-03-01

    Full Text Available Osteoarthritis, a degenerative joint disease, is the most commonrheumatic disorder mainly in a geriatric population. Manifestationsare pain, stiffness and functional loss in the affected joint.According to etiology it is classifi ed as primary (or idiopathicand secondary. Some risk factors for disease development aregenetics, race, age, sex, obesity, occupational activities andarticular biomechanics. Pathogenesis is the same for any cause orlocalization, being catabolic alterations, with synthesis, inhibitionand reparing intent of the cartilage matrix. Metalloproteinases andcytokines (IL-1,IL-6,TNF-α actions promote infl ammatory reactionand cartilage degradation. Pain, the most important symptom,does not correlate with radiologic fi ndings. Peripheral osteoarthritisoccurs predominantly in the knee, hip and hand. Diagnosis is basedon clinical features, laboratorial tests and radiological changes.Rheumatological associations’ guidelines for treatment includenon-pharmacologic (education, physiotherapy, assistive devices,and pharmacologic (analgesics, anti-infl ammatory drugs therapyand surgery. Arthroplasty seems to work better than medicines, butshould be used if other treatments have failed.

  20. Peripheral Mechanisms of Ischemic Myalgia

    Directory of Open Access Journals (Sweden)

    Luis F. Queme

    2017-12-01

    Full Text Available Musculoskeletal pain due to ischemia is present in a variety of clinical conditions including peripheral vascular disease (PVD, sickle cell disease (SCD, complex regional pain syndrome (CRPS, and even fibromyalgia (FM. The clinical features associated with deep tissue ischemia are unique because although the subjective description of pain is common to other forms of myalgia, patients with ischemic muscle pain often respond poorly to conventional analgesic therapies. Moreover, these patients also display increased cardiovascular responses to muscle contraction, which often leads to exercise intolerance or exacerbation of underlying cardiovascular conditions. This suggests that the mechanisms of myalgia development and the role of altered cardiovascular function under conditions of ischemia may be distinct compared to other injuries/diseases of the muscles. It is widely accepted that group III and IV muscle afferents play an important role in the development of pain due to ischemia. These same muscle afferents also form the sensory component of the exercise pressor reflex (EPR, which is the increase in heart rate and blood pressure (BP experienced after muscle contraction. Studies suggest that afferent sensitization after ischemia depends on interactions between purinergic (P2X and P2Y receptors, transient receptor potential (TRP channels, and acid sensing ion channels (ASICs in individual populations of peripheral sensory neurons. Specific alterations in primary afferent function through these receptor mechanisms correlate with increased pain related behaviors and altered EPRs. Recent evidence suggests that factors within the muscles during ischemic conditions including upregulation of growth factors and cytokines, and microvascular changes may be linked to the overexpression of these different receptor molecules in the dorsal root ganglia (DRG that in turn modulate pain and sympathetic reflexes. In this review article, we will discuss the

  1. Osteoarthritis: the genesis of pain.

    Science.gov (United States)

    Fu, Kai; Robbins, Sarah R; McDougall, Jason J

    2018-05-01

    OA is a painful joint disease that predominantly affects the elderly. Pain is the primary symptom of OA, and it can present as either intermittent or constant. OA pain mechanisms are complex and have only recently been determined. Both peripheral and central processes are involved in creating the OA pain experience, making targeted therapy problematic. Nociceptive, inflammatory and neuropathic pains are all known to occur in OA, but to varying degrees in a patient- and time-specific manner. A better understanding of these multifactorial components of OA pain will lead to the development of more effective and safer pain treatments.

  2. WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy.

    Science.gov (United States)

    Feng, Chengcheng; Xu, Lijuan; Guo, Shiyun; Chen, Qian; Shen, Yuguo; Zang, Deng; Ma, Li

    2018-01-01

    WenTong HuoXue Cream (WTHX-Cream) has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN). This study investigated the gene and protein expression of the pain-related molecule PLC- β 3 in the dorsal root ganglion (DRG) of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats) and DPN model (78 rats) groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC- β 3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC- β 3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC- β 3 mRNA and protein expression in the diabetic DRG of DPN rats.

  3. Towards a neurobiological understanding of pain in chronic pancreatitis: mechanisms and implications for treatment

    Directory of Open Access Journals (Sweden)

    Søren S. Olesen

    2017-12-01

    Conclusion:. Chronic pancreatitis is associated with abnormal processing of pain at the peripheral and central level of the pain system. This neurobiological understanding of pain has important clinical implications for treatment and prevention of pain chronification.

  4. Peripheral Primitive Neuroectodermal Tumor of the Stomach: A Case Report

    International Nuclear Information System (INIS)

    Park, Woon Ju; Cho, June Sik; Shin, Kyung Sook; Jeong, Hyung Yong; Noh; Seung Moo; Song, Kyu Sang

    2010-01-01

    Peripheral primitive neuroectodermal tumors (peripheral PNETs) are very rare and highly aggressive soft tissue malignancies originating from the neural crest. To the best of our knowledge, only a few cases of peripheral PNETs of the stomach have been reported in the literature. We report a case of large peripheral primitive neuroectodermal tumor of the stomach with MDCT findings in a 22-year-old man presenting epigastric pain and vomiting

  5. Defining post-stroke pain: diagnostic challenges

    NARCIS (Netherlands)

    Roosink, M.; Geurts, Alexander C.H.; IJzerman, Maarten Joost

    Recently, a new grading system for central post-stroke pain (CPSP) was proposed, which might be used to distinguish patients with stroke who have central neuropathic pain from patients who have peripheral pain. Accordingly, for a CPSP diagnosis, all other causes of pain have to be excluded. Although

  6. Dor: aspectos atuais da sensibilização periférica e central Dolor: aspectos actuales de la sensibilización periférica y central Pain: current aspects on peripheral and central sensitization

    Directory of Open Access Journals (Sweden)

    Anita Perpétua Carvalho Rocha

    2007-02-01

    conducción nerviosa central y periférica.BACKGROUND AND OBJECTIVES: Current research has focused on the biochemical and structural plasticity of the nervous system secondary to tissue injury. The mechanisms involved in the transition from acute to chronic pain are complex and involve the interaction of receptor systems and the flow of intracellular ions, second messenger systems, and new synaptic connections. The aim of this article was to discuss the new mechanisms concerning peripheral and central sensitization. CONTENTS: Tissue injury increases the response of nociceptors, known as sensitization or facilitation. These phenomena begin after the local release of inflammatory mediators and the activation of the cells of the immune system or specific receptors in the peripheral and central nervous system. CONCLUSIONS: Tissue and neuronal lesions result in sensitization of the nociceptors and facilitation of the central and peripheral nervous conduction.

  7. WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Chengcheng Feng

    2018-01-01

    Full Text Available WenTong HuoXue Cream (WTHX-Cream has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN. This study investigated the gene and protein expression of the pain-related molecule PLC-β3 in the dorsal root ganglion (DRG of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats and DPN model (78 rats groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC-β3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC-β3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC-β3 mRNA and protein expression in the diabetic DRG of DPN rats.

  8. Paclitaxel Plasma Concentration after the First Infusion Predicts Treatment-Limiting Peripheral Neuropathy.

    Science.gov (United States)

    Hertz, Daniel L; Kidwell, Kelley M; Vangipuram, Kiran; Li, Feng; Pai, Manjunath P; Burness, Monika; Griggs, Jennifer J; Schott, Anne F; Van Poznak, Catherine; Hayes, Daniel F; Lavoie Smith, Ellen M; Henry, N Lynn

    2018-04-27

    Purpose: Paclitaxel exposure, specifically the maximum concentration ( C max ) and amount of time the concentration remains above 0.05 μmol/L ( T c >0.05 ), has been associated with the occurrence of paclitaxel-induced peripheral neuropathy. The objective of this study was to validate the relationship between paclitaxel exposure and peripheral neuropathy. Experimental Design: Patients with breast cancer receiving paclitaxel 80 mg/m 2 × 12 weekly doses were enrolled in an observational clinical study (NCT02338115). Paclitaxel plasma concentration was measured at the end of and 16-26 hours after the first infusion to estimate C max and T c >0.05 Patient-reported peripheral neuropathy was collected via CIPN20 at each dose, and an 8-item sensory subscale (CIPN8) was used in the primary analysis to test for an association with T c >0.05 Secondary analyses were conducted using C max as an alternative exposure parameter and testing each parameter with a secondary endpoint of the occurrence of peripheral neuropathy-induced treatment disruption. Results: In 60 subjects included in the analysis, the increase in CIPN8 during treatment was associated with baseline CIPN8, cumulative dose, and relative dose intensity ( P 0.05 ( P = 0.27) nor C max ( P = 0.99). In analyses of the secondary endpoint, cumulative dose (OR = 1.46; 95% confidence interval (CI), 1.18-1.80; P = 0.0008) and T c >0.05 (OR = 1.79; 95% CI, 1.06-3.01; P = 0.029) or C max (OR = 2.74; 95% CI, 1.45-5.20; P = 0.002) were associated with peripheral neuropathy-induced treatment disruption. Conclusions: Paclitaxel exposure is predictive of the occurrence of treatment-limiting peripheral neuropathy in patients receiving weekly paclitaxel for breast cancer. Studies are warranted to determine whether exposure-guided dosing enhances treatment effectiveness and/or prevents peripheral neuropathy in these patients. Clin Cancer Res; 1-9. ©2018 AACR. ©2018 American Association for Cancer Research.

  9. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete

    2016-01-01

    Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...... TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence......, clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology...

  10. Orofacial pain conditions

    DEFF Research Database (Denmark)

    Pedersen, Anne Marie Lynge; Forssell, Heli; Grinde, Bjørn

    2016-01-01

    Pain of the oral mucosa is a common accompanying symptom of various oral mucosal lesions caused by local and systemic diseases. Pain of the oral mucosa is usually associated with a known cause of tissue damage, e.g. mucosal ulcer or erosion, and it generally responds to adequate treatment...... and dissolves after healing. Chronic pain, on the other hand, persists months and years after apparent tissue healing, and attempts to alleviate pain are challenging. Neuropathic pain occurs due to damage neurogenic structures in the peripheral and/or the central nervous system. It may occur in the absence...... of any obvious noxious stimuli, and in the oral mucosal, the pain is often described as tingling and burning. In the oral cavity, burning mouth syndrome (BMS) is presently considered to have neuropathic background. It is important for dental practitioners to have a clear understanding of the various...

  11. 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...

  12. Persistent postsurgical pain: risk factors and prevention

    DEFF Research Database (Denmark)

    Kehlet, Henrik; Jensen, Troels Staehelin; Woolf, Clifford J.

    2006-01-01

    therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop...... chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk...

  13. Habitual physical activity, peripheral neuropathy, foot deformities ...

    African Journals Online (AJOL)

    joint or leg pain), lack of equipment, and exercise partner(s).20. Yet, many of these ... peripheral neuropathy and lower limb functions among a group of Nigerian .... scale for inpatients of an orthopaedic rehabilitation ward found that interclass ...

  14. Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

    Science.gov (United States)

    Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

    2015-11-01

    Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks.

  15. 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...

  16. Cannabidiol Prevents the Development of Cold and Mechanical Allodynia in Paclitaxel-Treated Female C57Bl6 Mice

    OpenAIRE

    Ward, Sara Jane; Ramirez, Michael David; Neelakantan, Harshini; Walker, Ellen Ann

    2011-01-01

    The taxane chemotherapeutic paclitaxel frequently produces peripheral neuropathy in humans. Rodent models to investigate mechanisms and treatments are largely restricted to male rats, whereas female mouse studies are lacking. We characterized a range of paclitaxel doses on cold and mechanical allodynia in male and female C57Bl/6 mice. Because the nonpsycho-active phytocannabinoid cannabidiol attenuates other forms of neuropathic pain, we assessed its effect on paclitaxel-induced allodynia. Pa...

  17. Pain management in primary care – current perspectives

    African Journals Online (AJOL)

    vances in pain medicine and continue to follow the biomedical approach, which regards a specific pathway as ... factors, present and past psychological ... patients where no peripheral abnormal- ..... chronic pain: An integrative model for the.

  18. Anorectal and Pelvic Pain.

    Science.gov (United States)

    Bharucha, Adil E; Lee, Tae Hee

    2016-10-01

    Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  19. [Neither Descartes nor Freud? current pain models in psychosomatic medicine].

    Science.gov (United States)

    Egloff, N; Egle, U T; von Känel, R

    2008-05-14

    Models explaining chronic pain based on the mere presence or absence of peripheral somatic findings or which view pain of psychological origin when there is no somatic explanation, have their shortcomings. Current scientific knowledge calls for distinct pain concepts, which integrate neurobiological and neuropsychological aspects of pain processing.

  20. Possible involvement of the Sigma-1 receptor chaperone in chemotherapeutic-induced neuropathic pain.

    Science.gov (United States)

    Tomohisa, Mori; Junpei, Ohya; Aki, Masumoto; Masato, Harumiya; Mika, Fukase; Kazumi, Yoshizawa; Teruo, Hayashi; Tsutomu, Suzuki

    2015-11-01

    Previous studies have shown that ligands of the sigma-1 receptor chaperone (Sig-1R) regulate pain-related behaviors. Clinical use of chemotherapeutics is often compromised due to their adverse side effects, particularly those related to neuropathy. Previous studies have shown that repeated administration of oxaliplatin and paclitaxel produces neuropathy in rodents. Therefore, the aim of the present study was to clarify the involvement of the Sig-1R in chemotherapeutic-induced neuropathy by examining the effects of oxaliplatin and paclitaxel on the Sig-1R levels in the spinal cord, and by examining the effects of Sig-1R agonist and antagonist on oxaliplatin- and paclitaxel-induced neuropathy in rats. Chemotherapeutic-induced neuropathic pain was accompanied by a significant reduction of the Sig-1R level in the spinal cord. Furthermore, the administration of paclitaxel to CHO cells that stably overexpressed Sig-1Rs induced the clustering of Sig-1Rs. We also found that the Sig-1R agonist SA4503 potently inhibited the neuropathy induced by oxaliplatin- and paclitaxel, whereas this action was abolished by the Sig-1R antagonist NE-100. These results suggest that the reduction of Sig-1R activity is involved in chemotherapeutic-induced neuropathy, and the Sig-1R agonist SA4503 could serve as a potential candidate for the treatment of chemotherapeutic-induced neuropathy. © 2015 Wiley Periodicals, Inc.

  1. Peripheral cold acclimatization in Antarctic scuba divers.

    Science.gov (United States)

    Bridgman, S A

    1991-08-01

    Peripheral acclimatization to cold in scuba divers stationed at the British Antarctic Survey's Signy Station was investigated during a year in Antarctica. Five divers and five non-diver controls underwent monthly laboratory tests of index finger immersion in cold water for 30 min. Index finger pulp temperature and time of onset of cold-induced vasodilatation (CIVD) were measured. Pain was recorded with verbal and numerical psychophysical subjective pain ratings. Average finger temperatures and median finger pain from 6-30 min of immersion, maximum finger temperatures during the first CIVD cycle, and finger temperatures at the onset of CIVD were calculated. Comparison of the variables recorded from divers and non-divers were performed with analysis of variance. No significant differences were found among the variables recorded from divers and non-divers. From a review of the literature, divers have responses typical of non-cold-adapted Caucasians. There is, therefore, no evidence that Signy divers peripherally acclimatized to cold. We suggest that these findings occur because either the whole body cooling which divers undergo inhibits peripheral acclimatization or because of insufficiently frequent or severe cold exposure while diving. Further basic studies on the duration, frequency and severity of cold exposure necessary to induce peripheral cold acclimatization are required before this question can be satisfactorily answered.

  2. Peripheral Neuropathy and Nerve Compression Syndromes in Burns.

    Science.gov (United States)

    Strong, Amy L; Agarwal, Shailesh; Cederna, Paul S; Levi, Benjamin

    2017-10-01

    Peripheral neuropathy and nerve compression syndromes lead to substantial morbidity following burn injury. Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy. The symptoms manifest at various times from within one week of hospitalization to many months after wound closure. Peripheral neuropathy may be caused by vascular occlusion of vasa nervorum, inflammation, neurotoxin production leading to apoptosis, and direct destruction of nerves from the burn injury. This article discusses the natural history, diagnosis, current treatments, and future directions for potential interventions for peripheral neuropathy and nerve compression syndromes related to burn injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Propylthiouracil and peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Valentina Van Boekel

    1992-06-01

    Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

  4. Pain without nociceptors?

    DEFF Research Database (Denmark)

    Minett, Michael S; Falk, Sarah; Santana-Varela, Sonia

    2014-01-01

    Nav1.7, a peripheral neuron voltage-gated sodium channel, is essential for pain and olfaction in mice and humans. We examined the role of Nav1.7 as well as Nav1.3, Nav1.8, and Nav1.9 in different mouse models of chronic pain. Constriction-injury-dependent neuropathic pain is abolished when Nav1.......7 is deleted in sensory neurons, unlike nerve-transection-related pain, which requires the deletion of Nav1.7 in sensory and sympathetic neurons for pain relief. Sympathetic sprouting that develops in parallel with nerve-transection pain depends on the presence of Nav1.7 in sympathetic neurons. Mechanical...... and cold allodynia required distinct sets of neurons and different repertoires of sodium channels depending on the nerve injury model. Surprisingly, pain induced by the chemotherapeutic agent oxaliplatin and cancer-induced bone pain do not require the presence of Nav1.7 sodium channels or Nav1.8-positive...

  5. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  6. Functional abdominal pain syndrome.

    Science.gov (United States)

    Clouse, Ray E; Mayer, Emeran A; Aziz, Qasim; Drossman, Douglas A; Dumitrascu, Dan L; Mönnikes, Hubert; Naliboff, Bruce D

    2006-04-01

    Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher comorbidity with psychiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely represents a heterogeneous group of disorders, peripheral neuropathic pain mechanisms, alterations in endogenous pain modulation systems, or both may be involved in any one patient. The diagnosis of FAPS is made on the basis of positive symptom criteria and a longstanding history of symptoms; in the absence of alarm symptoms, an extensive diagnostic evaluation is not required. Management is based on a therapeutic physician-patient relationship and empirical treatment algorithms using various classes of centrally acting drugs, including antidepressants and anticonvulsants. The choice, dose, and combination of drugs are influenced by psychiatric comorbidities. Psychological treatment options include psychotherapy, relaxation techniques, and hypnosis. Refractory FAPS patients may benefit from a multidisciplinary pain clinic approach.

  7. The pharmacotherapy of low back pain

    African Journals Online (AJOL)

    pain: Cancer, Cauda Equina Syndrome, Herniated intervertebral disc, severe or progressive ... Is associated with new bowel or bladder problems. 7. Is accompanied by .... may inhibit carbonic anhydrase and the NMDA receptor. Peripherally it ...

  8. 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.

  9. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  10. Does Transcranial Direct Current Stimulation Combined with Peripheral Electrical Stimulation Have an Additive Effect in the Control of Hip Joint Osteonecrosis Pain Associated with Sickle Cell Disease? A Protocol for a One-Session Double Blind, Block-Randomized Clinical Trial.

    Science.gov (United States)

    Lopes, Tiago da Silva; Silva, Wellington Dos Santos; Ribeiro, Sânzia B; Figueiredo, Camila A; Campbell, Fernanda Q; Daltro, Gildasio de Cerqueira; Valenzuela, Antônio; Montoya, Pedro; Lucena, Rita de C S; Baptista, Abrahão F

    2017-01-01

    Chronic pain in Sickle Cell Disease (SCD) is probably related to maladaptive plasticity of brain areas involved in nociceptive processing. Transcranial Direct Current Stimulation (tDCS) and Peripheral Electrical Stimulation (PES) can modulate cortical excitability and help to control chronic pain. Studies have shown that combined use of tDCS and PES has additive effects. However, to date, no study investigated additive effects of these neuromodulatory techniques on chronic pain in patients with SCD. This protocol describes a study aiming to assess whether combined use of tDCS and PES more effectively alleviate pain in patients with SCD compared to single use of each technique. The study consists of a one-session double blind, block-randomized clinical trial (NCT02813629) in which 128 participants with SCD and femoral osteonecrosis will be enrolled. Stepwise procedures will occur on two independent days. On day 1, participants will be screened for eligibility criteria. On day 2, data collection will occur in four stages: sample characterization, baseline assessment, intervention, and post-intervention assessment. These procedures will last ~5 h. Participants will be divided into two groups according to homozygous for S allele (HbSS) ( n = 64) and heterozygous for S and C alleles (HbSC) ( n = 64) genotypes. Participants in each group will be randomly assigned, equally, to one of the following interventions: (1) active tDCS + active PES; (2) active tDCS + sham PES; (3) sham tDCS + active PES; and (4) sham tDCS + sham PES. Active tDCS intervention will consist of 20 min 2 mA anodic stimulation over the primary motor cortex contralateral to the most painful hip. Active PES intervention will consist of 30 min sensory electrical stimulation at 100 Hz over the most painful hip. The main study outcome will be pain intensity, measured by a Visual Analogue Scale. In addition, electroencephalographic power density, cortical maps of the gluteus maximus muscle elicited by

  11. Iohexol and ioxaglate in peripheral angiography

    International Nuclear Information System (INIS)

    Stiris, M.G.; Laerum, F.

    1987-01-01

    A double-blind, cross-over trial of the non-ionic, low-osmolar contrast medium iohexol (Omnipaque) and the ionic, low-osmolar medium ioxaglate (Hexabrix) at concentrations of 300 mg I/ml was carried out in 107 consecutive patients with arterial insufficiency of the lower limbs. The purpose of the study was to observe possible 'carry-over' effects from any of the contrast media, and to evaluate patient discomfort such as pain, adverse reactions, or effect on peripheral blood pressure. No carry-over effect was seen. Ioxaglate caused less injection pain and heat sensations than iohexol, and showed less effect on the systemic blood pressure. (orig.)

  12. The McKenzie method compared with manipulation when used adjunctive to information and advice in low back pain patients presenting with centralization or peripheralization. A randomized controlled trial

    DEFF Research Database (Denmark)

    Petersen, Tom; Larsen, Kristian; Nordsteen, Jan

    2011-01-01

    as a reduction of at least 5 points or an absolute score below 5 points on the Roland Morris Questionnaire. Secondary outcomes were reduction in disability and pain, global perceived effect, general health, mental health, lost work time, and medical care utilization.Results. Both treatment groups showed...

  13. Efficacy of spinal cord stimulators in treating peripheral neuropathy: a case series.

    Science.gov (United States)

    Abd-Elsayed, Alaa; Schiavoni, Nick; Sachdeva, Harsh

    2016-02-01

    Peripheral neuropathy is a common cause of pain, and it is increasing in prevalence. Peripheral neuropathic pain is very hard to treat and can be resistant to multiple pain management modalities. Our series aimed at testing the efficacy of spinal cord stimulators (SCSs) in treating resistant painful peripheral neuropathy. Case 1: A 79-year-old man presented to our clinic with long-standing history of painful peripheral diabetic neuropathy resistant to conservative management. After failure of all possible modalities, we offered the patient an SCS trial that was very successful, and we proceeded with the permanent implant that continued to help with his pain and allowed the patient to wean down his medications. Case 2: A 60-year-old man presented with chronic peripheral neuropathy secondary to HIV, patient failed all conservative and procedural management. Patient then had an SCS trial that relieved his pain significantly. Unfortunately, we did not proceed with the implant due to deterioration of the patient general health. Case 3: A 39-year-old woman presented with painful peripheral neuropathy secondary to chemotherapy for breast cancer. After failure of medication management and procedures, patient had a SCS trial that improved her pain and we then proceeded with performing the permanent implant that controlled her pain. We presented 3 cases with chronic painful peripheral neuropathy secondary to HIV, diabetes mellitus, and chemotherapy that was resistant to conservative pain management and procedures that was successfully treated with neurostimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. NEUROBIOLOGICAL AND CLINICAL RELATIONSHIP BETWEEN PSYCHIATRIC DISORDERS AND CHRONIC PAIN

    OpenAIRE

    Barš, Marijana; Đorđević, Veljko; Gregurek, Rudolf; Bulajić, Maša

    2010-01-01

    Pain is one of the most ubiquitious problems of today's world, its impact being far-reaching. Current conceptualizations of pain medicine adopt a bio-psycho-social perspective. In this model, pain is best described as an interactive, psycho-physiological behaviour pattern that cannot be divided into independet psycho-social and physical components. Neurophysiologic substrates of the pain experience can be broken down into the pain transmission elements emanating from peripheral, spinal, and s...

  15. Taxane-Induced Peripheral Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Roser Velasco

    2015-04-01

    Full Text Available Taxane-derived agents are chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on the ability of the drugs to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often manifested as painful neuropathy experienced during treatment, and it is sometimes irreversible. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior to the initiation of treatment. The present review aims to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with the development of taxane-induced neuropathy.

  16. 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.

  17. Postoperative pain

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B

    1993-01-01

    also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree......Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...

  18. 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...

  19. Functional abdominal pain.

    Science.gov (United States)

    Grover, Madhusudan; Drossman, Douglas A

    2010-10-01

    Functional abdominal pain syndrome (FAPS) is a relatively less common functional gastrointestinal (GI) disorder defined by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods (Drossman Gastroenterology 130:1377-1390, 2006), which points to a more centrally targeted (spinal and supraspinal) basis for the symptoms. However, FAPS is frequently confused with irritable bowel syndrome and other functional GI disorders in which abdominal pain is associated with eating and bowel movements. FAPS also differs from chronic abdominal pain associated with entities such as chronic pancreatitis or chronic inflammatory bowel disease, in which the pain is associated with peripherally acting factors (eg, gut inflammation or injury). Given the central contribution to the pain experience, concomitant psychosocial disturbances are common and strongly influence the clinical expression of FAPS, which also by definition is associated with loss of daily functioning. These factors make it critical to use a biopsychosocial construct to understand and manage FAPS, because gut-directed treatments are usually not successful in managing this condition.

  20. Diagnostic approach to peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Misra Usha

    2008-01-01

    Full Text Available Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG. EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG. Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.

  1. Vasculitic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Mona Amini

    2014-02-01

    Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

  2. Mechanisms and management of functional abdominal pain

    OpenAIRE

    Farmer, Adam D; Aziz, Qasim

    2014-01-01

    Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory sys...

  3. Orofacial pain management: current perspectives

    Directory of Open Access Journals (Sweden)

    Romero-Reyes M

    2014-02-01

    Full Text Available Marcela Romero-Reyes, James M Uyanik Orofacial and Head Pain Service, Department of Oral and Maxillofacial Pathology Radiology and Medicine, New York University College of Dentistry, New York, NY, USA Abstract: Some of the most prevalent and debilitating pain conditions arise from the structures innervated by the trigeminal system (head, face, masticatory musculature, temporomandibular joint and associated structures. Orofacial pain (OFP can arise from different regions and etiologies. Temporomandibular disorders (TMD are the most prevalent orofacial pain conditions for which patients seek treatment. Temporomandibular disorders include a number of clinical problems that involve the masticatory musculature, the temporomandibular joint (TMJ or both. Trigeminal neuropathic pain conditions can arise from injury secondary to dental procedures, infection, neoplasias, or disease or dysfunction of the peripheral and/or central nervous system. Neurovascular disorders, such as primary headaches, can present as chronic orofacial pain, such as in the case of facial migraine, where the pain is localized in the second and third division of the trigeminal nerve. Together, these disorders of the trigeminal system impact the quality of life of the sufferer dramatically. A multidisciplinary pain management approach should be considered for the optimal treatment of orofacial pain disorders including both non-pharmacological and pharmacological modalities. Keywords: pain, orofacial, neuropathic, TMD, trigeminal, headache

  4. Pain and pain mechanisms in patients with inflammatory arthritis

    DEFF Research Database (Denmark)

    Rifbjerg-Madsen, S; Christensen, A W; Christensen, R

    2017-01-01

    completed the PDQ (RA: 3,826, PsA: 1,180, SpA: 1,093). 52% of all patients and 63% of PDQ-completers had VAS pain score ≥ 30 mm. The distribution of the PDQ classification-groups (18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More patients with PsA had PDQ score >18....... The objectives were to quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic features) among Danish arthritis patients using the PDQ, and to assess the association with on-going inflammation. METHODS: The PDQ was included onto the DANBIO touch screens at 22 departments of Rheumatology......28-CRP and VAS pain but not with indicators of peripheral inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in mechanism-based pain treatment....

  5. Donating Peripheral Blood Stem Cells

    Science.gov (United States)

    ... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

  6. Peripheral Neuropathy: Symptoms and Signs

    Science.gov (United States)

    ... Utah Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... more slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

  7. Pain Perception in Buddhism Perspective.

    Science.gov (United States)

    Waikakul, Waraporn; Waikakul, Saranatra

    2016-08-01

    Dhamma, which Lord Buddha has presented to people after his enlightenment, analyzes every phenomenon and objects into their ultimate elements. The explanation of sensory system is also found in a part of Dhamma named Abhidhammapitaka, the Book of the Higher Doctrine in Buddhism. To find out the relationship between explanation of pain in the present neuroscience and the explanation of pain in Abhidhamma, the study was carried out by the use of a comprehensive review. The comparisons were in terms of peripheral stimulation, signal transmission, modulation, perception, suffering, determination and decision making for the responding to pain. We found that details of the explanation on pain mechanism and perception in Abhidhamma could associate well with our present scientific knowledge. Furthermore, more refinement information about the process and its function in particular aspects of pain perception were provided in Abhidhammapitaka.

  8. Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management.

    Science.gov (United States)

    Watson, James C; Dyck, P James B

    2015-07-01

    Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  9. [Operative treatment of painful neuromas].

    Science.gov (United States)

    Stokvis, Annemieke; Coert, J Henk

    2011-01-01

    3-5% of patients with traumatic or iatrogenic peripheral nerve injury develop a painful neuroma, especially following trauma of small cutaneous sensory nerve branches. Neuroma pain is difficult to treat and often leads to loss of function and reduction of quality of life. Patients with a painful neuroma present with spontaneous electric, shooting or burning pain, allodynia, hyperalgesia and cold intolerance. The diagnosis is based on the medical history and physical examination, supplemented by Tinel's test and a diagnostic nerve blockade. Lasting pain relief is possible by means of surgical neuroma treatment performed by a plastic surgeon. Surgical treatment consists of repair or denervation of the nerve with relocation of the nerve stump in bone or muscle tissue or a vein. Referral of neuroma patients without delay to a plastic surgeon or multidisciplinary consultation is important, because the symptoms become increasingly difficult to treat over time. 3-5% of patients with traumatic or iatrogenic peripheral nerve injury develop a painful neuroma, especially following trauma of small cutaneous sensory nerve branches. Neuroma pain is difficult to treat and often leads to loss of function and reduction of quality of life. Patients with a painful neuroma present with spontaneous electric, shooting or burning pain, allodynia, hyperalgesia and cold intolerance. The diagnosis is based on the medical history and physical examination, supplemented by Tinel's test and a diagnostic nerve blockade. Lasting pain relief is possible by means of surgical neuroma treatment performed by a plastic surgeon. Surgical treatment consists of repair or denervation of the nerve with relocation of the nerve stump in bone or muscle tissue or a vein. Referral of neuroma patients without delay to a plastic surgeon or multidisciplinary consultation is important, because the symptoms become increasingly difficult to treat over time.

  10. Peripheral Ulcerative Keratitis

    Science.gov (United States)

    ... oval in shape. Diagnosis A doctor's evaluation Sometimes culture The diagnosis of peripheral ulcerative keratitis is suspected when the doctor sees the affected cornea in a person who also has a severe and/or long- ...

  11. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  12. Cannabinoids and Pain

    Directory of Open Access Journals (Sweden)

    J Michael Walker

    2001-01-01

    Full Text Available Cannabinoids have been used to treat pain for many centuries. However, only during the past several decades have rigorous scientific methods been applied to understand the mechanisms of cannabinoid action. Cannabinoid receptors were discovered in the late 1980s and have been found to mediate the effects of cannabinoids on the nervous system. Several endocannabinoids were subsequently identified. Many studies of cannabinoid analgesia in animals during the past century showed that cannabinoids block all types of pain studied. These effects were found to be due to the suppression of spinal and thalamic nociceptive neurons, independent of any actions on the motor systems. Spinal, supraspinal and peripheral sites of cannabinoid analgesia have been identified. Endocannabinoids are released upon electrical stimulation of the periaqueductal gray, and in response to inflammation in the extremities. These observations and others thus suggest that a natural function of cannabinoid receptors and their endogenous ligands is to regulate pain sensitivity. The therapeutic potential of cannabinoids remains an important topic for future investigations, with previous work suggesting utility in clinical studies of cancer and surgical pain. New modes of delivery and/or new compounds lacking the psychotropic properties of the standard cannabinoid ligands offer promise for cannabinoid therapeutics for pain.

  13. 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.

  14. Promoting peripheral myelin repair

    OpenAIRE

    Zhou, Ye; Notterpek, Lucia

    2016-01-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

  15. Role of the radiologist in the management of pain

    International Nuclear Information System (INIS)

    Quinn, S.F.; Murtagh, F.R.; Chatfield, R.; Kori, S.; Kavanagh, J.; Clark, R.A.

    1987-01-01

    Radiologists are taking an expanding role in the management of pain. The procedures most commonly used at our institution are facet blocks, peripheral nerve blocks, peripheral nerve ablations, ganglion ablations, chemoinfusions, chemoembolizations, and embolizations alone. CT is used for the facet, ganglion, and peripheral nerve procedures. The techniques for these procedures will be stressed, as meticulous technique is imperative. The radiologist must work closely with the attending clinician to determine both the neurologic level and to monitor therapy. The University of South Florida pain team flow sheet and pain evaluation method is presented

  16. Glia and pain: is chronic pain a gliopathy?

    Science.gov (United States)

    Ji, Ru-Rong; Berta, Temugin; Nedergaard, Maiken

    2013-12-01

    Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. Although widely detected in chronic pain resulting from nerve trauma, inflammation, cancer, and chemotherapy in rodents, and more recently, human immunodeficiency virus-associated neuropathy in human beings, glial reaction (activation state 1) is not thought to mediate pain sensitivity directly. Instead, activation states 2 to 4 have been demonstrated to enhance pain sensitivity via a number of synergistic neuro-glial interactions. Glial mediators have been shown to powerfully modulate excitatory and inhibitory synaptic transmission at presynaptic, postsynaptic, and extrasynaptic sites. Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of "gliopathy," that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions. Copyright © 2013 International Association for the

  17. Neural and psychosocial mechanisms of pain sensitivity in fibromyalgia.

    Science.gov (United States)

    English, Brian

    2014-06-01

    Fibromyalgia is a chronic musculoskeletal pain disorder that affects an estimated 5 million adults in the U.S. The hallmark is burning, searing, tingling, shooting, stabbing, deep aching, or sharp pain. Fibromyalgia is generally considered to be a "central sensitivity syndrome" where central sensitization is regarded as the cause of pain in its own right. Nonetheless, the case continues to be made that all central and spatially distributed peripheral components of fibromyalgia pain would fade if the peripheral generators could be silenced. Although neural mechanisms are clearly important in pain sensitivity, cognitive and social mechanisms also need to be considered. The aim of this review is to examine four mechanisms responsible for heightened pain sensitivity in fibromyalgia: peripheral sensitization, central sensitization, cognitive-emotional sensitization, and interpersonal sensitization. The purpose of framing the review in terms of pain sensitivity in fibromyalgia is to highlight that different mechanisms of sensitization are appropriately regarded as intervening variables when it comes to understanding individual differences in the experience of pain. The paper concludes by considering the implications of the findings of the review for explanations of fibromyalgia pain by nurses working in multidisciplinary teams. The trend appears to be able to explain the cause of fibromyalgia pain in terms of sensitization per se. The recommended alternative is to explain fibromyalgia pain in terms of changes in pain sensitivity and the role of underlying neural and psychosocial mechanisms. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  18. Chronic Pain and Neuropathy Following Adjuvant Chemotherapy

    DEFF Research Database (Denmark)

    Ventzel, Lise; Madsen, Caspar S; Karlsson, Páll

    2017-01-01

    Objective: To determine symptoms and characteristics of chronic sensory neuropathy in patients treated with oxaliplatin and docetaxel, including patterns of somatosensory abnormalities, pain descriptors, and psychological functioning. Design: A retrospective cross-sectional study. Setting: A chro...... mechanisms useful for future studies in the tailored treatment of prevention of chemotherapy-induced peripheral neuropathy and pain.......Objective: To determine symptoms and characteristics of chronic sensory neuropathy in patients treated with oxaliplatin and docetaxel, including patterns of somatosensory abnormalities, pain descriptors, and psychological functioning. Design: A retrospective cross-sectional study. Setting......: A chronic pain research center. Subjects: Thirty-eight patients with chronic peripheral pain and/or dysesthesia following chemotherapy. Methods:  Sensory profiles, psychological functioning, and quality of life were assessed using standardized questionnaires. In addition, standardized quantitative sensory...

  19. CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Piekarz Andrew D

    2012-07-01

    Full Text Available Abstract Background The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2 to bind to N-type voltage-activated calcium channels (CaV2.2 [Brittain et al. Nature Medicine 17:822–829 (2011]. Results and discussion Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP release compared to vehicle control. Conclusions Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of

  20. Mechanisms of Acupuncture-Electroacupuncture on Persistent Pain

    Science.gov (United States)

    Zhang, Ruixin; Lao, Lixing; Ren, Ke; Berman, Brian M.

    2014-01-01

    In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue-injury (inflammatory), nerve-injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2–10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce pro-inflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal n-methyl-d-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management that can forestall the side effects of often-debilitating pharmaceuticals. PMID:24322588

  1. Sexual pain.

    Science.gov (United States)

    Boardman, Lori A; Stockdale, Colleen K

    2009-12-01

    Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain.

  2. The burden and characteristics of peripheral arterial disease in ...

    African Journals Online (AJOL)

    The Edinburgh Claudication Question- naire was used to .... ous amputations and assess risk factors of PAD. The ..... longs the onset of claudication pain thus allowing the patient to walk ... ECQ may not be the best tool to adapt to diagnose early. PAD in our ... ciety consensus for management of peripheral arte- rial disease.

  3. Hopes for the Future of Pain Control.

    Science.gov (United States)

    Bannister, Kirsty; Kucharczyk, Mateusz; Dickenson, Anthony H

    2017-12-01

    Here we aim to present an accessible review of the pharmacological targets for pain management, and succinctly discuss the newest trends in pain therapy. A key task for current pain pharmacotherapy is the identification of receptors and channels orchestrating nociception. Notwithstanding peripheral alterations in the receptors and channels following pathophysiological events, the modulatory mechanisms in the central nervous system are also fundamental to the regulation of pain perception. Bridging preclinical and clinical studies of peripheral and central components of pain modulation, we present the different types of pain and relate these to pharmacological interventions. We firstly highlight the roles of several peripheral nociceptors, such as NGF, CGRP, sodium channels, and TRP-family channels that may become novel targets for therapies. In the central nervous system, the roles of calcium channels and gabapentinoids as well as NMDA receptors in generating excitability are covered including ideas on central sensitization. We then turn to central modulatory systems and discuss opioids and monoamines. We aim to explain the importance of central sensitization and the dialogue of the spinal circuits with the brain descending modulatory controls before discussing a mechanism-based effectiveness of antidepressants in pain therapy and their potential to modulate the descending controls. Emphasizing the roles of conditioned pain modulation and its animal's equivalent, diffuse noxious inhibitory controls, we discuss these unique descending modulations as a potential tool for understanding mechanisms in patients suffering from pain. Mechanism-based therapy is the key to picking the correct treatments and recent clinical studies using sensory symptoms of patients as surrogates for underlying mechanisms can be used to subgroup patients and reveal actions of drugs that may be lost when studying heterogenous groups of patients. Key advances in the understanding of basic pain

  4. 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.

  5. Pelvic Pain

    Science.gov (United States)

    ... OLPP) Office of Science Policy, Reporting, and Program Analysis (OSPRA) Division of Extramural Research (DER) Extramural Scientific ... treat my pain? Can pelvic pain affect my emotional well-being? How can I cope with long- ...

  6. Neck pain

    Science.gov (United States)

    ... cause of neck pain is muscle strain or tension. Most often, everyday activities are to blame. Such ... of a heart attack , such as shortness of breath, sweating, nausea, vomiting, or arm or jaw pain. ...

  7. Peripheral Sympathectomy for Raynaud's Phenomenon: A Salvage Procedure

    Directory of Open Access Journals (Sweden)

    Wen-Her Wang

    2006-10-01

    Full Text Available We retrospectively reviewed the effectiveness of peripheral sympathectomy for severe Raynaud's phenomenon. In this study, a total of 14 digits from six patients with chronic digital ischemic change were included. All patients had pain, ulcer, or gangrenous change in the affected digits and were unresponsive to pharmacologic or other nonsurgical therapies. In all cases, angiography showed multifocal arterial lesions, so microvascular reconstruction was unfeasible. Peripheral sympathectomy was performed as a salvage procedure to prevent digit amputation. The results were analyzed according to reduction of pain, healing of ulcers, and prevention of amputation. In 12 of the 14 digits, the ulcers healed and amputation was avoided. In the other two digits, the ulcers improved and progressive gangrene was limited. As a salvage procedure for Raynaud's phenomenon recalcitrant to conservative treatment, peripheral sympathectomy improves perfusion to ischemic digits and enables amputation to be avoided.

  8. Patellofemoral Pain.

    Science.gov (United States)

    Dutton, Rebecca A; Khadavi, Michael J; Fredericson, Michael

    2016-02-01

    Patellofemoral pain is characterized by insidious onset anterior knee pain that is exaggerated under conditions of increased patellofemoral joint stress. A variety of risk factors may contribute to the development of patellofemoral pain. It is critical that the history and physical examination elucidate those risk factors specific to an individual in order to prescribe an appropriate and customized treatment plan. This article aims to review the epidemiology, risk factors, diagnosis, and management of patellofemoral pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Pain Management in Functional Gastrointestinal Disorders

    Directory of Open Access Journals (Sweden)

    Antonio Vigano

    1995-01-01

    Full Text Available Pain is a common feature in functional gastrointestinal disorders (FGID. An abnormally low visceral sensory threshold, as well as a number of central, spinal and peripheral pain-modulating abnormalities, have been proposed for this syndrome. Clinical aspects of pain associated with irritable esophagus, functional dyspepsia, biliary dysmotility, inflammatory bowel syndrome and proctalgia fugax are reviewed. Because of its unclear pathophysiology, pain expression is the main target for the successful assessment and management of symptomatic FGID. The sensory, cognitive and affective components of pain intensity expression need to be addressed in the context of a good physician-patient rapport. A multidisciplinary team approach is ideal for the smaller subset of patients with severe and disabling symptoms. Although pharmacotherapy may target specific functional disorders, the role of behavioural techniques and psychotherapy appears much more important for pain management in FGID. Functional performance and quality of life improvement, rather than pain intensity, are the main therapeutic goals in these patients.

  10. [Pain in humans: experimental facts and hypotheses].

    Science.gov (United States)

    Cesaro, P

    1994-09-15

    The description of painful phenomena in humans has to take into account its different components: sensory component (relevant to nociception), affective and emotional components. Nociceptor's (physiology is best understood with electrophysiological and neurochemical methods allowing a clear description of hyperalgesia, with its peripheral and spinal mechanisms. A functional model is partly available to explain allodynia, spontaneous burning pain and lightning pain, the three main consequences following deafferentation. At the thalamo-cortical level, one can describe nociceptive pathways and other pathways or neuronal networks involved in the affective and emotional components of pain.

  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. Orofacial pain management: current perspectives.

    Science.gov (United States)

    Romero-Reyes, Marcela; Uyanik, James M

    2014-01-01

    Some of the most prevalent and debilitating pain conditions arise from the structures innervated by the trigeminal system (head, face, masticatory musculature, temporomandibular joint and associated structures). Orofacial pain (OFP) can arise from different regions and etiologies. Temporomandibular disorders (TMD) are the most prevalent orofacial pain conditions for which patients seek treatment. Temporomandibular disorders include a number of clinical problems that involve the masticatory musculature, the temporomandibular joint (TMJ) or both. Trigeminal neuropathic pain conditions can arise from injury secondary to dental procedures, infection, neoplasias, or disease or dysfunction of the peripheral and/or central nervous system. Neurovascular disorders, such as primary headaches, can present as chronic orofacial pain, such as in the case of facial migraine, where the pain is localized in the second and third division of the trigeminal nerve. Together, these disorders of the trigeminal system impact the quality of life of the sufferer dramatically. A multidisciplinary pain management approach should be considered for the optimal treatment of orofacial pain disorders including both non-pharmacological and pharmacological modalities.

  14. Phantom Pain

    Science.gov (United States)

    ... Because this is yet another version of tangled sensory wires, the result can be pain. A number of other factors are believed to contribute to phantom pain, including damaged nerve endings, scar tissue at the site of the amputation and the physical memory of pre-amputation pain in the affected area. ...

  15. Management of chronic visceral pain

    DEFF Research Database (Denmark)

    Olesen, Anne E; Farmer, Adam D; Olesen, Søren S

    2016-01-01

    Despite marked differences in underlying pathophysiology, the current management of visceral pain largely follows the guidelines derived from the somatic pain literature. The effective management of patients with chronic visceral pain should be multifaceted, including both pharmacological...... and psychological interventions, thereby providing a mechanism-orientated approach to treatment. Patients can frequently become disenfranchised, and subsequently disengaged, with healthcare providers leading to repeated consultations. Thus, a key aspect of management is to break this cycle by validating patients......' symptoms, adopting an empathic approach and taking time to educate patients. To optimize treatment and outcomes in chronic visceral pain we need to move away from approaches exclusively based on dealing with peripheral nociceptive input toward more holistic strategies, taking into account alterations...

  16. Peripheral epithelial odontogenic tumor

    International Nuclear Information System (INIS)

    Carzoglio, J.; Tancredi, N.; Capurro, S.; Ravecca, T.; Scarrone, P.

    2006-01-01

    A new case of peripheral epithelial odontogenic tumor (Pindborg tumor) is reported. It is localized in the superior right gingival region, a less frequent site, and has the histopathological features previously reported. Immunochemical studies were performed, revealing a differential positive stain to cytokeratins in tumor cells deeply seated in the tumor mass, probably related to tumoral cell heterogeneity.Interestingly, in this particular case S-100 protein positive reactivity was also detected in arborescent cells intermingled with tumoral cells, resembling Langerhans cells. Even though referred in the literature in central Pindborg tumors, no references were found about their presence in peripheral tumors, like the one that is presented here

  17. Peripheral neurostimulation for control of intractable occipital neuralgia.

    Science.gov (United States)

    Weiner, R L; Reed, K L

    1999-07-01

    Objective. To present a novel approach for treatment of intractable occipital neuralgia using percutaneous peripheral nerve electrostimulation techniques. Methods. Thirteen patients underwent 17 implant procedures for medically refractory occipital neuralgia. A subcutaneous electrode placed transversely at the level of C1 across the base of the occipital nerve trunk produced paresthesias and pain relief covering the regions of occipital nerve pain Results. With follow-up ranging from 1-½ to 6 years, 12 patients continue to report good to excellent response with greater than 50% pain control and requiring little or no additional medications. The 13th patient (first in the series) was subsequently explanted following symptom resolution. Conclusions. In patients with medically intractable occipital neuralgia, peripheral nerve electrostimulation subcutaneously at the level of C1 appears to be a reasonable alternative to more invasive surgical procedures following failure of more conservative therapies.

  18. Spontaneous pain attacks: neuralgic pain

    NARCIS (Netherlands)

    de Bont, L.G.

    2006-01-01

    Paroxysmal orofacial pains can cause diagnostic problems, especially when different clinical pictures occur simultaneously. Pain due to pulpitis, for example, may show the same characteristics as pain due to trigeminal neuralgia would. Moreover, the trigger point of trigeminal neuralgia can either

  19. 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.

  20. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  1. 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.

  2. 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

  3. Peripheral Artery Disease

    Science.gov (United States)

    ... pressure High blood cholesterol Coronary heart disease Stroke Metabolic syndrome Screening and Prevention Taking action to control your risk factors can help prevent or delay peripheral artery disease (P.A.D.) and its complications. Know your family history of health problems related to P.A. ...

  4. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Pain. Part 2a: Trigeminal Anatomy Related to Pain.

    Science.gov (United States)

    Renton, Tara; Egbuniwe, Obi

    2015-04-01

    In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.

  6. Effects of water avoidance stress on peripheral and central responses during bladder filling in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP research network study.

    Directory of Open Access Journals (Sweden)

    Zhuo Wang

    Full Text Available Stress plays a role in the exacerbation and possibly the development of functional lower urinary tract disorders. Chronic water avoidance stress (WAS in rodents is a model with high construct and face validity to bladder hypersensitive syndromes, such as interstitial cystitis/bladder pain syndrome (IC/BPS, characterized by urinary frequency and bladder hyperalgesia and heightened stress responsiveness. Given the overlap of the brain circuits involved in stress, anxiety, and micturition, we evaluated the effects chronic stress has on bladder function, as well as its effects on regional brain activation during bladder filling. Female Wistar-Kyoto rats were exposed to WAS (10 days or sham paradigms. One day thereafter, cystometrograms were obtained during titrated bladder dilation, with visceromotor responses (VMR recorded simultaneously. Cerebral perfusion was assessed during passive bladder distension (20-cmH2O following intravenous administration of [14C]-iodoantipyrine. Regional cerebral blood flow was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains with statistical parametric mapping. WAS animals compared to controls demonstrated a decreased pressure threshold and visceromotor threshold triggering the voiding phase. At 20-cmH2O, VMR was significantly greater in WAS animals compared to controls. WAS animals showed greater activation in cortical regions of the central micturition circuit, including the posterior cingulate, anterior retrosplenial, somatosensory, posterior insula, orbital, and anterior secondary ("supplementary" motor cortices, as well as in the thalamus, anterior hypothalamus, parabrachial and Barrington nuclei, and striatum. Seed analysis showed increased functional connectivity of WAS compared to control animals of the posterior cingulate cortex to the pontine parabrachial nucleus; of the Barrington nucleus to the anterior dorsal midline and ventrobasilar thalamus and somatosensory and

  7. Pain genes.

    Directory of Open Access Journals (Sweden)

    Tom Foulkes

    2008-07-01

    Full Text Available Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors signal the existence of tissue damage to the central nervous system (CNS, where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

  8. Synovial sarcoma mimicking benign peripheral nerve sheath tumor

    Energy Technology Data Exchange (ETDEWEB)

    Larque, Ana B.; Nielsen, G.P.; Chebib, Ivan [Massachusetts General Hospital and Harvard Medical School, Department of Pathology, Boston, MA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2017-11-15

    To assess the radiographic and clinicopathologic features of synovial sarcoma of the nerve that were clinically or radiologically interpreted as benign peripheral nerve sheath tumor. Five patients with synovial sarcoma arising from the peripheral nerve and interpreted clinically and radiologically as peripheral nerve sheath tumors were identified. Clinicopathologic and imaging features were evaluated. There were three females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular bundle. On histologic examination, most tumors were monophasic synovial sarcoma (4/5). At the time of surgery, all tumors were noted to arise along or within a peripheral nerve. All patients were alive with no evidence of disease with median follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign peripheral nerve sheath tumors of the extremities were identified during the same time period. Primary synovial sarcoma of the nerve can mimic peripheral nerve sheath tumors clinically and on imaging and should be included in the differential diagnosis for tumors arising from peripheral nerves. (orig.)

  9. Corticostriatal Regulation of Acute Pain

    Directory of Open Access Journals (Sweden)

    Erik Martinez

    2017-05-01

    Full Text Available The mechanisms for acute pain regulation in the brain are not well understood. The prefrontal cortex (PFC provides top-down control of emotional processes, and it projects to the nucleus accumbens (NAc. This corticostriatal projection forms an important regulatory pathway within the brain’s reward system. Recently, this projection has been suggested to control both sensory and affective phenotypes specifically associated with chronic pain. As this projection is also known to play a role in the transition from acute to chronic pain, we hypothesized that this corticostriatal circuit can also exert a modulatory function in the acute pain state. Here, we used optogenetics to specifically target the projection from the PFC to the NAc. We tested sensory pain behaviors with Hargreaves’ test and mechanical allodynia, and aversive pain behaviors with conditioned place preference (CPP test. We found that the activation of this corticostriatal circuit gave rise to bilateral relief from peripheral nociceptive inputs. Activation of this circuit also provided important control for the aversive response to transient noxious stimulations. Hence, our results support a novel role for corticostriatal circuitry in acute pain regulation.

  10. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  11. Calcitonin gene-related peptide and pain

    DEFF Research Database (Denmark)

    Schou, Wendy Sophie; Ashina, Sait; Amin, Faisal Mohammad

    2017-01-01

    and cerebrospinal fluid in subjects with musculoskeletal pain. A randomized clinical trial on monoclonal antibody, which selectively binds to and inhibits the activity of CGRP (galcanezumab) in patients with osteoarthritis knee pain, failed to demonstrate improvement of pain compared with placebo. No studies......BACKGROUND: Calcitonin gene-related peptide (CGRP) is widely distributed in nociceptive pathways in human peripheral and central nervous system and its receptors are also expressed in pain pathways. CGRP is involved in migraine pathophysiology but its role in non-headache pain has not been...... clarified. METHODS: We performed a systematic literature search on PubMed, Embase and ClinicalTrials.gov for articles on CGRP and non-headache pain covering human studies including experimental studies and randomized clinical trials. RESULTS: The literature search identified 375 citations of which 50...

  12. Complex Regional Pain Syndrome and Treatment Approaches

    Directory of Open Access Journals (Sweden)

    Neslihan Gokcen

    2013-08-01

    Full Text Available Complex Regional Pain Syndrome is a symptom complex including severe pain which is disproportioned by the initiating event. Formerly, it was known as reflex sympathetic dystropy, Sudeck’s atrophy and algoneurodystrophy. There are two types of complex regional pain syndrome (CPRS. CRPS type 1 (Reflex sympathetic dystropy occurs after a minor trauma of the extremities, CRPS type 2 (Causalgia occurs following peripheral nevre injury. Diagnosis is made according to the history, symptoms and physical findings of the patients. Patient education, physical therapy and medical treatment are the most common treatment approaches of complex regional pain syndrome. The aim of this review is to revise the treatment options ofcomplex regional pain syndrome, as well as to overview the new treatment approaches and options for the refractory complex regional pain syndrome cases. [Archives Medical Review Journal 2013; 22(4.000: 514-531

  13. Peripheral giant cell granuloma: A review of 123 cases

    Directory of Open Access Journals (Sweden)

    Niloofar Shadman

    2009-01-01

    Full Text Available Background: Peripheral giant cell granuloma is one of the reactive hyperplastic lesions of the oral cavity, which originates from the periosteum or periodontal membrane following local irritation or chronic trauma. The purpose of this study was to present the clinical characteristics of peripheral gi-ant cell granuloma in a group of Iranian population. Methods: A series of 123 consecutive confirmed cases of peripheral giant cell granuloma after biopsy were evaluated. Age, sex, anatomic location, consistency, etiologic factor, pain and bleeding history, color, surface texture, and pedicle situation were recorded and were analyzed by chi-square test and values were considered to be significant if P < 0.05. Results: Age ranged from 6 to 75 years (mean 33 years. Women affected more than men (M/F 1:1.1. Peripheral giant cell granuloma was seen in the mandible more than in the maxilla and in the anterior region more than in the posterior region. In most cases, lesions were pink, pedunculated and had non-ulcerated surface. In less than half of the cases, there was no history of bleeding and also pain was rarely reported. Calculus was the most common etiologic factor. Conclusion: The results confirmed that the clinical features of peripheral giant cell granuloma in a group of Iranian population are almost similar to those reported by other investigators.

  14. Pain and Consciousness in Humans. Or Why Pain Subserves the Identity and Self-representation

    Directory of Open Access Journals (Sweden)

    Irene Venturella

    2016-08-01

    Full Text Available Traditional definitions of pain assume that an individual learns about pain through verbal usages related to the experience of injury in early life. This emphasis on the verbal correlates of pain restricts our understanding of pain to the context of adult human consciousness. In this paper we instead support the idea that our understanding of pain originates in neonatal experience and is not merely a verbally determined phenomenon. We also challenge the definition of pain as a merely sensory message related to peripheral tissue trauma. We aim to move beyond this definition by considering the relationship between the centre (Central Nervous System and periphery, taking into account certain phenomena such as phantom limbs and interoception. We show that pain helps an individual to develop a sense of awareness of himself immersed in a social context, and is thus a complex and adaptive phenomenon, that supports bodily integrity and social behavior.

  15. Peripheral orbit model

    CERN Document Server

    Hara, Yasuo

    1975-01-01

    Peripheral orbit model, in which an incoming hadron is assumed to revolve in a peripheral orbit around a target hadron, is discussed. The non-diffractive parts of two-body reaction amplitudes of hadrons are expressed in terms of the radius, width an absorptivity of the orbit. The radius of the orbit is about 1 fm and the width of the orbit is determined by the range of the interaction between the hadrons. The model reproduces all available experimental data on differential cross-sections and polarizations of $K^{-}p\\to K^{-}p$ and $\\bar K^{\\circ}n$ reactions for all angles successfully. This contribution is not included in the proceedings since it will appear in Progress of Theoretical Physics Vol. 51 (1974) No 2. Any person interested in the subject may apply for reprints to the author.

  16. Ejaculatory pain

    DEFF Research Database (Denmark)

    Aasvang, Eske K; Møhl, Bo; Kehlet, Henrik

    2007-01-01

    . The psychosexual interview revealed no major psychosexual disturbances and concluded that the pain was of somatic origin. All patients with ejaculatory pain had experienced major negative life changes and deterioration in their overall quality of life and sexual function as a result of the hernia operation...

  17. Breast Pain

    Science.gov (United States)

    ... result in the development of breast cysts. Breast trauma, prior breast surgery or other factors localized to the breast can lead to breast pain. Breast pain may also start outside the breast — in the chest wall, muscles, joints or heart, for example — and ...

  18. Painful shoulder

    Directory of Open Access Journals (Sweden)

    Benno Ejnismann

    2008-03-01

    Full Text Available Many factors can be involved in the painful shoulder. Beyond articularcauses other pathologies such as artrosis, periarticular diseases as rotadorcuff tears, long head of the biceps tendinitis, adhesive capsulitis, calcifyingtendinitis, degenerative arthritis of the acromioclavicular joint, cervicalradiculopathy and nervous injuries can cause pain in the shoulder.

  19. Orofacial Pain

    Science.gov (United States)

    ... aligned teeth can have trouble because the muscles work harder to bring the teeth together, causing strain. Pain also can be caused by clenching or grinding teeth, trauma to the head and neck or poor ergonomics. ; Some people may experience pain in the ears, ...

  20. Neck Pain

    Science.gov (United States)

    ... Vomiting Nausea and Vomiting in Infants and Children Neck Pain Neck Swelling Shortness of Breath Shortness of Breath ... worse or doesn’t get better. Start OverDiagnosisYour pain may be from DEGENERATIVE CERVICAL ARTHRITIS, a disorder that affects the bones and ...

  1. 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.

  2. 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

  3. Muscle function and origin of pain in fibromyalgia

    DEFF Research Database (Denmark)

    Bennett, R M; Jacobsen, Søren

    1994-01-01

    It may be concluded that both peripheral and central mechanisms may operate in the pathophysiology of both impaired muscle function and pain in FM. These mechanisms may in part be attributable to physical deconditioning and disuse of muscle secondary to the characteristic pain and fatigue so ofte...

  4. 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

  5. AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions.

    Science.gov (United States)

    Paice, Judith A; Mulvey, Matt; Bennett, Michael; Dougherty, Patrick M; Farrar, John T; Mantyh, Patrick W; Miaskowski, Christine; Schmidt, Brian; Smith, Thomas J

    2017-03-01

    Chronic cancer pain is a serious complication of malignancy or its treatment. Currently, no comprehensive, universally accepted cancer pain classification system exists. Clarity in classification of common cancer pain syndromes would improve clinical assessment and management. Moreover, an evidence-based taxonomy would enhance cancer pain research efforts by providing consistent diagnostic criteria, ensuring comparability across clinical trials. As part of a collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) and the American Pain Society (APS), the ACTTION-APS Pain Taxonomy initiative worked to develop the characteristics of an optimal diagnostic system. After the establishment of these characteristics, a working group consisting of clinicians and clinical and basic scientists with expertise in cancer and cancer-related pain was convened to generate core diagnostic criteria for an illustrative sample of 3 chronic pain syndromes associated with cancer (ie, bone pain and pancreatic cancer pain as models of pain related to a tumor) or its treatment (ie, chemotherapy-induced peripheral neuropathy). A systematic review and synthesis was conducted to provide evidence for the dimensions that comprise this cancer pain taxonomy. Future efforts will subject these diagnostic categories and criteria to systematic empirical evaluation of their feasibility, reliability, and validity and extension to other cancer-related pain syndromes. The ACTTION-APS chronic cancer pain taxonomy provides an evidence-based classification for 3 prevalent syndromes, namely malignant bone pain, pancreatic cancer pain, and chemotherapy-induced peripheral neuropathy. This taxonomy provides consistent diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms for these potentially serious cancer pain conditions that can be extended and applied with other cancer

  6. Chronic pain and evoked responses in the brain: A magnetoencephalographic study in Complex Regional Pain Syndrome I and II

    NARCIS (Netherlands)

    Theuvenet, P.J.

    2012-01-01

    Complex Regional Pain Syndrome (CRPS) type I and II are chronic pain syndromes with comparable symptoms, only in CRPS II a peripheral nerve injury is present. No objective tests are currently available to differentiate the two types which hampers diagnosis and treatment. Non-invasive brain imaging

  7. Pain in rheumatic diseases: how relevant is it?

    Science.gov (United States)

    Sarzi-Puttini, P; Atzeni, F; Salaffi, F

    2014-06-06

    Pain, a complex phenomenon influenced by a series of genetic, biological, psychological and social factors, is a major component of many rheumatological conditions and the result of physiological interactions between central and peripheral nervous system signalling. It may be acute or chronic (generally defined as lasting ≥ three months): acute pain is often primarily attributable to inflammation and/or damage to peripheral structures (i.e. nociceptive input), whereas chronic pain is more likely to be due to input from the central nervous system (CNS). The many different aspects of pain mean that rheumatologists and other clinicians need to have enough expertise to diagnose the type of pain correctly and treat it appropriately. However, most rheumatologists receive little formal training concerning contemporary theories of pain processing or management, and this may affect the clinical results of any specific target therapy.

  8. Pain in rheumatic diseases: how relevant is it?

    Directory of Open Access Journals (Sweden)

    P. Sarzi-Puttini

    2014-06-01

    Full Text Available Pain, a complex phenomenon influenced by a series of genetic, biological, psychological and social factors, is a major component of many rheumatological conditions and the result of physiological interactions between central and peripheral nervous system signalling. It may be acute or chronic (generally defined as lasting ≥ three months: acute pain is often primarily attributable to inflammation and/or damage to peripheral structures (i.e. nociceptive input, whereas chronic pain is more likely to be due to input from the central nervous system (CNS. The many different aspects of pain mean that rheumatologists and other clinicians need to have enough expertise to diagnose the type of pain correctly and treat it appropriately. However, most rheumatologists receive little formal training concerning contemporary theories of pain processing or management, and this may affect the clinical results of any specific target therapy.

  9. Idiopathic facial pain related with dental implantation

    Directory of Open Access Journals (Sweden)

    Tae-Geon Kwon

    2016-06-01

    Full Text Available Chronic pain after dental implantation is rare but difficult issue for the implant practitioner. Patients with chronic pain who had been performed previous implant surgery or related surgical intervention sometimes accompany with psychological problem and difficult to adequately manage. According to the International Classification of Headache Disorders (ICHD 3rd eds, Cepalagia 2013, painful neuropathies and other facial pains are subdivided into the 12 subcategories; 13.1. Trigeminal neuralgia; 13.2 Glossopharyngeal neuralgia; 13.3 Nervus intermedius (facial nerve neuralgia; 13.4 Occipital neuralgia; 13.5 Optic neuritis; 13.6 Headache attributed to ischaemic ocular motor nerve palsy; 13.7 Tolosa-Hunt syndrome; 13.8 Paratrigeminal oculo-sympathetic (Raeder’s syndrome; 13.9 Recurrent painful ophthalmoplegic neuropathy; 13.10 Burning Mouth Syndrome (BMS; 13.11 Persistent Idiopathic Facial Pain (PIFP; 13.12 Central neuropathic pain. Chronic orofacial pain after dental implant surgery can be largely into the two main categories that can be frequently encountered in clinical basis ; 1 Neuropathic pain, 2 Idiopathic pain. If there is no direct evidence of the nerve injury related with the implant surgery, the clinician need to consider the central cause of pain instead of the peripheral cause of the pain. There might be several possibilities; 1 Anaesthesia dolorosa, 2 Central post-stroke pain, 3 Facial pain attributed to multiple sclerosis, 4 Persistent idiopathic facial pain (PIFP, 5 Burning mouth syndrome. In this presentation, Persistent idiopathic facial pain (PIFP, the disease entity that can be frequently encountered in the clinic would be discussed. Persistent idiopathic facial pain (PIFP can be defined as “persistent facial and/or oral pain, with varying presentations but recurring daily for more than 2 hours per day over more than 3 months, in the absence of clinical neurological deficit”. ‘Atypical’ pain is a diagnosis of

  10. Contemporary pain management in total knee arthroplasty.

    Science.gov (United States)

    Khanasuk, Yutthana; Ngarmukos, Srihatach

    2012-10-01

    Pain management has become a very important part of postoperative care for total knee arthroplasty patients. Contemporary pain control has evolved from high-dose opioid in the past to state-of-the-art multimodal regimens. These include multiple non-opioid medication such as NSAIDs, COX-2 inhibitors, and gabapentinoid, and novel anesthetic techniques such as preemptive analgesia and ultrasound-guided peripheral nerve blocks. Another method which is gaining popularity is intraarticular injection of anesthetic cocktail during surgery. Pre-op education can also help patients cope with their pain better.

  11. Prospective surveillance of phlebitis associated with peripheral intravenous catheters.

    Science.gov (United States)

    Malach, Tal; Jerassy, Ziona; Rudensky, Bernard; Schlesinger, Yechiel; Broide, Etty; Olsha, Oded; Yinnon, Amos M; Raveh, David

    2006-06-01

    Guidelines have been published for prevention of phlebitis associated with peripheral intravenous catheters (IVC), but this complication continues to occur. We sought to determine the rate of phlebitis associated with peripheral IVCs to identify predictors for phlebitis and to isolate pathogenic bacteria from phlebitic catheter tips. Nine-point prevalence studies were conducted during the years 1996-2003 of all hospitalized patients with a peripheral IVC. During the last 3 surveys, conducted in 2003, phlebitic lines were removed, and, for each line, 1 to 2 nonphlebitic lines, in place for 48 to 72 hours, were removed and cultured as controls. In between these surveys, findings and guidelines for improvement were distributed to the staff. During these surveys, 40% +/- 8% of hospitalized patients had a peripheral IVC. The rate of peripheral IVC-associated phlebitis decreased from 12.7% (20/157) in 1998 to 2.6% (5/189) in 2003 (P phlebitis included pain (P phlebitis associated with peripheral intravenous catheters decreased significantly throughout the study period. The identification of predictors for phlebitis and the dissemination of this information in an educational drive may have contributed to this improvement.

  12. Ethanol sclerotherapy of peripheral venous malformations

    Energy Technology Data Exchange (ETDEWEB)

    Rimon, U. E-mail: rimonu@sheba.health.gov.il; Garniek, A.; Galili, Y.; Golan, G.; Bensaid, P.; Morag, B

    2004-12-01

    Background: venous malformations are congenital lesions that can cause pain, decreased range of movement, compression on adjacent structures, bleeding, consumptive coagulopathy and cosmetic deformity. Sclerotherapy alone or combined with surgical excision is the accepted treatment in symptomatic malformations after failed treatment attempts with tailored compression garments. Objectives: to report our experience with percutaneous sclerotherapy of peripheral venous malformations with ethanol 96%. Patients and methods: 41 sclerotherapy sessions were performed on 21 patients, aged 4-46 years, 15 females and 6 males. Fourteen patients were treated for painful extremity lesions, while five others with face and neck lesions and two with giant chest malformations had treatment for esthetic reasons. All patients had a pre-procedure magnetic resonance imaging (MRI) study. In all patients, 96% ethanol was used as the sclerosant by direct injection using general anesthesia. A minimum of 1-year clinical follow-up was performed. Follow-up imaging studies were performed if clinically indicated. Results: 17 patients showed complete or partial symptomatic improvement after one to nine therapeutic sessions. Four patients with lower extremity lesions continue to suffer from pain and they are considered as a treatment failure. Complications were encountered in five patients, including acute pulmonary hypertension with cardiovascular collapse, pulmonary embolus, skin ulcers (two) and skin blisters. All patients fully recovered. Conclusion: sclerotherapy with 96% ethanol for venous malformations was found to be effective for symptomatic improvement, but serious complications can occur.

  13. Ethanol sclerotherapy of peripheral venous malformations

    International Nuclear Information System (INIS)

    Rimon, U.; Garniek, A.; Galili, Y.; Golan, G.; Bensaid, P.; Morag, B.

    2004-01-01

    Background: venous malformations are congenital lesions that can cause pain, decreased range of movement, compression on adjacent structures, bleeding, consumptive coagulopathy and cosmetic deformity. Sclerotherapy alone or combined with surgical excision is the accepted treatment in symptomatic malformations after failed treatment attempts with tailored compression garments. Objectives: to report our experience with percutaneous sclerotherapy of peripheral venous malformations with ethanol 96%. Patients and methods: 41 sclerotherapy sessions were performed on 21 patients, aged 4-46 years, 15 females and 6 males. Fourteen patients were treated for painful extremity lesions, while five others with face and neck lesions and two with giant chest malformations had treatment for esthetic reasons. All patients had a pre-procedure magnetic resonance imaging (MRI) study. In all patients, 96% ethanol was used as the sclerosant by direct injection using general anesthesia. A minimum of 1-year clinical follow-up was performed. Follow-up imaging studies were performed if clinically indicated. Results: 17 patients showed complete or partial symptomatic improvement after one to nine therapeutic sessions. Four patients with lower extremity lesions continue to suffer from pain and they are considered as a treatment failure. Complications were encountered in five patients, including acute pulmonary hypertension with cardiovascular collapse, pulmonary embolus, skin ulcers (two) and skin blisters. All patients fully recovered. Conclusion: sclerotherapy with 96% ethanol for venous malformations was found to be effective for symptomatic improvement, but serious complications can occur

  14. ASIC3: A Lactic Acid Sensor for Cardiac Pain

    Directory of Open Access Journals (Sweden)

    D.C. Immke

    2001-01-01

    Full Text Available Angina, the prototypic vasoocclusive pain, is a radiating chest pain that occurs when heart muscle gets insufficient blood because of coronary artery disease. Other examples of vasoocclusive pain include the acute pain of heart attack and the intermittent pains that accompany sickle cell anemia and peripheral artery disease. All these conditions cause ischemia � insufficient oxygen delivery for local metabolic demand — and this releases lactic acid as cells switch to anaerobic metabolism. Recent discoveries demonstrate that sensory neurons innervating the heart are richly endowed with an ion channel that is opened by, and perfectly tuned for, the lactic acid released by muscle ischemia[1,2].

  15. Daspsone Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    P A Sarojini

    1988-01-01

    Full Text Available A 24 year old lady being treated with 300 mg of dapsone daily for dermatitits herpetiformis, developed weakness and wasting of muscles of feet with claw hand deformity and t drop, 2 months tater. Neurological examination and nerve conduction studies conformed the presence of a peripheral motor neuropathy. Dapsone was discontinued and the patient was treated with cotrimatoxazole, gluten-free diet and supportive therapy. This satisfactorily controlled the dermatological lesion without adversely affecting the resolution of her neuropthy. Symptomatic improvement reported by the patient was confirmed by EMG and nerve conduction studies.

  16. Peripheral ossifying fibroma

    Directory of Open Access Journals (Sweden)

    Ameet Mani

    2010-01-01

    Full Text Available The peripheral ossifying fibroma (POF is an exophytic gingival mass of fibrous connective tissue covered with a surface epithelium associated with the formation of randomly dispersed foci of a mineralized product consisting of bone, cementum-like tissue, or dystrophic calcifications having a recurrent rate of nearly 20%. It is one of the most common reactive gingival lesions, which have often been called by the generic term "epulis." This case report describes the clinical and histopathological findings of POF, its differential diagnosis, and treatment.

  17. Review article: the functional abdominal pain syndrome.

    Science.gov (United States)

    Sperber, A D; Drossman, D A

    2011-03-01

    Functional abdominal pain syndrome (FAPS) is a debilitating disorder with constant or nearly constant abdominal pain, present for at least 6 months and loss of daily functioning. To review the epidemiology, pathophysiology and treatment of FAPS. A literature review using the keywords: functional abdominal pain, chronic abdominal pain, irritable bowel syndrome and functional gastrointestinal disorders. No epidemiological studies have focused specifically on FAPS. Estimates of prevalence range from 0.5% to 1.7% and tend to show a female predominance. FAPS pathophysiology appears unique in that the pain is caused primarily by amplified central perception of normal visceral input, rather than by enhanced peripheral stimulation from abdominal viscera. The diagnosis of FAPS is symptom-based in accordance with the Rome III diagnostic criteria. These criteria are geared to identify patients with severe symptoms as they require constant or nearly constant abdominal pain with loss of daily function and are differentiated from IBS based on their non-association with changes in bowel habit, eating or other gut-related events. As cure is not feasible, the aims of treatment are reduced suffering and improved quality of life. Treatment is based on a biopsychosocial approach with a therapeutic patient-physician partnership at its base. Therapeutic options include central nonpharmacological and pharmacological modalities and peripheral modalities. These can be combined to produce an augmentation effect. Although few studies have assessed functional abdominal pain syndrome or its treatment specifically, the treatment strategies outlined in this paper appear to be effective. © 2011 Blackwell Publishing Ltd.

  18. Craniofacial Pain: Brainstem Mechanisms

    Directory of Open Access Journals (Sweden)

    Barry J Sessle

    1996-01-01

    Full Text Available This article reviews recent research advances in animals that have identified critical neural elements in the brainstem receiving and transmitting craniofacial nociceptive inputs, as well as some of the mechanisms involved in the modulation and plasticity of nociceptive transmission. Nociceptive neurones in the trigeminal (V brainstem sensory nuclear complex can be classified as nociceptive-specific (NS or wide dynamic range (WDR. Some of these neurones respond exclusively to sensory inputs evoked by stimulation of facial skin or oral mucosa and have features suggesting that they are critical neural elements involved in the ability to localize an acute superficial pain and sense its intensity and duration. Many of the V brainstem nociceptive neurones, however, receive convergent inputs from afferents supplying deep craniofacial tissues (eg, dural vessel, muscle and skin or mucosa. These neurones are likely involved in deep pain, including headache, because few nociceptive neurones receive inputs exclusively from afferents supplying these tissues. These extensive convergent input patterns also appear to be important factors in pain spread and referral, and in central mechanisms underlying neuroplastic changes in V neuronal properties that may occur with injury and inflammation. For example, application of the small fibre excitant and inflammatory irritant mustard oil into the temporomandibular joint, masseter or tongue musculature induces a prolonged but reversible enhancement of responses to cutaneous and deep afferent inputs of most WDR and NS neurones. These effects may be accompanied by increased electromyographic activity reflexly induced in the masticatory muscles by mustard oil, and involve endogenous N-methyl-D-aspartate and opioid neurochemical mechanisms. Such peripherally induced modulation of brainstem nociceptive neuronal properties reflects the functional plasticity of the central V system, and may be involved in the development of

  19. How Is Pain Managed?

    Science.gov (United States)

    ... Detection- Goggins Lab Sol Goldman Center Discussion Board Pain Management Pain is a very common symptom in patients ... of pain. Pain Assessment The first step in pain management is a thorough assessment. Your healthcare provider will ...

  20. Sigma-1 receptor and inflammatory pain.

    Science.gov (United States)

    Gris, Georgia; Cobos, Enrique José; Zamanillo, Daniel; Portillo-Salido, Enrique

    2015-06-01

    The sigma-1 receptor (Sig-1R) is a unique ligand-regulated molecular chaperone that interacts with several protein targets such as G protein-coupled receptors and ion channels to modulate their activity. Sig-1R is located in areas of the central and peripheral nervous system that are key to pain control. Previous preclinical studies have suggested a potential therapeutic use of Sig-1R antagonists for the management of neuropathic pain. Recent studies using pharmacological and genetic tools have explored the role of Sig-1R in inflammatory pain conditions. Mice lacking the Sig-1R have shown different patterns of phenotypic responses to inflammatory injury. Systemic or peripheral administration of several Sig-1R antagonists, including the selective Sig-1R antagonist S1RA, inhibited both mechanical and thermal hypersensitivity in several preclinical models of inflammatory pain. These recent studies are summarized in the present commentary. Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain.

  1. Pain Management

    Science.gov (United States)

    ... Funding Funding Opportunities (NIH Guide) Forms and Deadlines Electronic Research Admin (eRA) Grants Policy OER News About ... remains the most commonly used pain reliever. The French physician, Dr. Albert Schweitzer, proclaimed in 1931 that, “ ...

  2. Back Pain

    Science.gov (United States)

    ... addition, there doesn't appear to be one type of mattress that's best for people with back pain. It's probably a ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  3. Ankle Pain

    Science.gov (United States)

    ... home remedies for a while. Seek immediate medical attention if you: Have severe pain or swelling Have ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  4. Abdominal Pain

    Science.gov (United States)

    ... or pain in your chest Seek immediate medical attention Have someone drive you to urgent care or ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  5. Testicle Pain

    Science.gov (United States)

    ... is more common in adolescents. Seek immediate medical attention if you have: Sudden, severe testicle pain Testicle ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  6. Gastric pain

    African Journals Online (AJOL)

    drugs and drug classes are also linked to a range of mechanisms through which the drugs ... meal, occurring several times per ... Burning or distressing pain, relieved by food ..... antimicrobial agents, and several other drug interactions are.

  7. Penis pain

    Science.gov (United States)

    Pain - penis ... Bites, either human or insect Cancer of the penis Erection that does not go away (priapism) Genital herpes Infected hair follicles Infected prosthesis of the penis Infection under the foreskin of uncircumcised men ( balanitis ) ...

  8. Joint pain

    Science.gov (United States)

    ... or conditions. It may be linked to arthritis , bursitis , and muscle pain . No matter what causes it, ... Autoimmune diseases such as rheumatoid arthritis and lupus Bursitis Chondromalacia patellae Crystals in the joint: Gout (especially ...

  9. Elbow pain

    Science.gov (United States)

    ... the cause, but may involve: Antibiotics Corticosteroid shots Manipulation Pain medicine Physical therapy Surgery (last resort) Alternative ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  10. Knee pain

    Science.gov (United States)

    ... Fracture of the kneecap or other bones. Iliotibial band syndrome . Injury to the thick band that runs from your hip to the outside ... of your knee pain. When to Contact a Medical Professional Call your provider if: You cannot bear ...

  11. Abdominal Pain

    Science.gov (United States)

    ... I find more information and related topics? Functional Abdominal Pain (English, French or Spanish)—from The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). Gastro Kids , a ...

  12. Flank pain

    Science.gov (United States)

    ... how to do these exercises at home. Nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy may be prescribed for flank pain caused by spinal arthritis. Antibiotics are used to treat most kidney infections. You ...

  13. Elbow Pain

    Science.gov (United States)

    ... tear damage than are many other joints. Seek emergency care if you have: An obvious deformity in ... http://www.mayoclinic.org/symptoms/elbow-pain/basics/definition/SYM-20050874 . Mayo Clinic Footer Legal Conditions and ...

  14. Arm Pain

    Science.gov (United States)

    ... be a sign of a heart attack. Seek emergency treatment if you have: Arm, shoulder or back ... http://www.mayoclinic.org/symptoms/arm-pain/basics/definition/SYM-20050870 . Mayo Clinic Footer Legal Conditions and ...

  15. PERIPHERAL BLOCK ANESTHESIA OF UPPER EXTREMITY AND ITS COMPLICATIONS

    Directory of Open Access Journals (Sweden)

    Hakan Tapar

    2012-09-01

    Full Text Available Successful peripheral blocks and selection of appropriate technique according to surgery is possible with a good knowledge of anatomy. Regional peripheral block anesthesia of upper extremity which applied by single injection to plexus brachialis is the most recommended method of anesthesia in daily surgical procedures. The most important advantages of peripheral nerve blocks which are type of regional anesthesia according to general anesthesia and central blocks are less effect to respiration and hemodynamics and shortness of recovery time. If a plexus brachialis catheter is placed, control of pain is provided without using systemic narcotic analgesic. With these advantages; rare life threatening potential complications can be seen which are pneumothorax, hematoma, neuritis, allergy, systemic and neurologic complications. In this compilation we aimed to review again the complications of upper extremity nerve blocks according to block type. [J Contemp Med 2012; 2(3.000: 195-200

  16. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

    International Nuclear Information System (INIS)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

    2010-01-01

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  17. Neonatal pain

    Science.gov (United States)

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  18. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  19. 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

  20. 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.

  1. Polineuropatia periférica dolorosa após cirurgia bariátrica: Relato de casos Polineuropatía periférica dolorosa después de la cirugía bariátrica: Relato de casos Painful peripheral polyneuropathy after bariatric surgery: Case reports

    Directory of Open Access Journals (Sweden)

    Miriam Seligman Menezes

    2008-06-01

    /psychiatric. Among the neurological complications, peripheral neuropathies are important due to their high incidence. The objective of this report was to stress the importance of this type of complication, in which the initial manifestation might be neuropathic pain followed or accompanied by motor involvement, and whose prognosis depends on early diagnosis and treatment. CASE REPORTS: The case of three patients were reported, two females and one male, who underwent bariatric surgery (restrictive method - Roux-en-Y gastric bypass and developed, postoperatively, peripheral neuropathy with neuropathic pain as the initial symptom, with posterior or concomitant motor involvement. Electroneuromyography demonstrated in all three cases a sensitive-motor axonal peripheral neuropathy. In two patients, the fibular nerves were severely affected. In common, they all had an important weight loss in a short period of time before developing neurological symptoms. CONCLUSIONS: Neurological complications are one of the most feared complications of bariatric surgeries. Nutritional deficiencies secondary to the surgery are the most important factors in its pathogeny. Nutritional surveillance, avoidance of severe and fast weight loss, and nutritional supplements are fundamental to avoid complications, especially neurological complications.

  2. Chinese herbal medicine for diabetic peripheral neuropathy.

    Science.gov (United States)

    Chen, Wei; Zhang, Yin; Li, Xinxue; Yang, Guoyan; Liu, Jian Ping

    2013-10-06

    Chinese herbal medicine is frequently used for treating diabetic peripheral neuropathy in China. Many controlled trials have been undertaken to investigate its efficacy.This is an update of a Cochrane review that was first published in the year 2011. To assess the beneficial effects and harms of Chinese herbal medicine for people with diabetic peripheral neuropathy. On 14 May 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register CENTRAL (2012, Issue 4 in The Cochrane Library), MEDLINE (January 1966 to May 2012), EMBASE (January 1980 to May 2012), AMED (January 1985 to May 2012) and in October 2012, the Chinese Biomedical Database (CBM) (1979 to October 2012), Chinese National Knowledge Infrastructure Database (CNKI) (1979 to October 2012), and VIP Chinese Science and Technique Journals Database (1989 to October 2012). We searched for unpublished literature in the Chinese Conference Papers Database, and Chinese Dissertation Database (from inception to October 2012). There were no language or publication restrictions. We included randomised controlled trials of Chinese herbal medicine (with a minimum of four weeks treatment duration) for people with diabetic peripheral neuropathy compared with placebo, no intervention, or conventional interventions. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. Two authors independently extracted data and evaluated trial quality. We contacted study authors for additional information. Forty-nine randomised trials involving 3639 participants were included. All trials were conducted and published in China. Thirty-eight different herbal medicines were tested in these trials, including four single herbs (extracts from a single herb), eight traditional Chinese patent medicines, and 26 self concocted Chinese herbal compound prescriptions. The trials reported on global symptom improvement (including improvement in numbness or pain) and changes in nerve conduction

  3. Chronic widespread pain in spondyloarthritis

    Directory of Open Access Journals (Sweden)

    F. Atzeni

    2014-06-01

    Full Text Available The pain associated with spondyloarthritis (SpA can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP that characterises fibromyalgia (FM. The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs.

  4. Pain in fibromyalgia and related conditions

    Directory of Open Access Journals (Sweden)

    G. Cassisi

    2014-06-01

    Full Text Available Pain is the hallmark symptom of fibromyalgia (FM and other related syndromes, but quite different from that of other rheumatic diseases, which depends on the degree of damage or inflammation in peripheral tissues. Sufferers are often defined as patients with chronic pain without an underlying mechanistic cause, and these syndromes and their symptoms are most appropriately described as “central pain”, “neuropathic pain”, “nonnociceptive pain” or “central sensitivity syndromes”. The pain is particular, regional or widespread, and mainly relates to the musculoskeletal system; hyperalgesia or allodynia are typical. Its origin is currently considered to be distorted pain or sensory processing, rather than a local or regional abnormality. FM is probably the most important and extensively described central pain syndrome, but the characteristics and features of FM-related pain are similar in other disorders of particular interest for rheumatologists, such as myofascial pain syndromes and temporo-mandibular joint disorders, and there is also an intriguing overlap between FM and benign joint hypermobility syndrome. This suggests that the distinctive aspects of pain in these idiopathic or functional conditions is caused by central nervous system hypersensitivity and abnormalities. Pharmacological and non-pharmacological therapies have been suggested for the treatment of these conditions, but a multidisciplinary approach is required in order to reduce the abnormal cycle of pain amplification and the related maladaptive and self-limiting behaviours.

  5. Mechanisms-based classifications of musculoskeletal pain: part 3 of 3: symptoms and signs of nociceptive pain in patients with low back (± leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-08-01

    As a mechanisms-based classification of pain \\'nociceptive pain\\' (NP) refers to pain attributable to the activation of the peripheral receptive terminals of primary afferent neurones in response to noxious chemical, mechanical or thermal stimuli. The symptoms and signs associated with clinical classifications of NP have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of NP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol after which their pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various symptoms and signs. A regression analysis identified a cluster of seven clinical criteria predictive of NP, including: \\'Pain localised to the area of injury\\/dysfunction\\

  6. Thoracic epidural steroid injection for rib fracture pain.

    Science.gov (United States)

    Rauchwerger, Jacob J; Candido, Kenneth D; Deer, Timothy R; Frogel, Jonathan K; Iadevaio, Robert; Kirschen, Neil B

    2013-06-01

    Treatment for rib fracture pain can be broadly divided into pharmacologic approaches with oral and/or parenteral medication and interventional approaches utilizing neuraxial analgesia or peripheral nerve blocks to provide pain relief. Both approaches attempt to control nociceptive and neuropathic pain secondary to osseous injury and nerve insult, respectively. Success of treatment is ultimately measured by the ability of the selected modality to decrease pain, chest splinting, and to prevent sequelae of injury, such as pneumonia. Typically, opioids and NSAIDs are the drugs of first choice for acute pain because of ease of administration, immediate onset of action, and rapid titration to effect. In contrast, neuropathic pain medications have a slower onset of action and are more difficult to titrate to therapeutic effect. Interventional approaches include interpleural catheters, intercostal nerve blocks, paravertebral nerve blocks, and thoracic and lumbar epidural catheters. Each intervention has its own inherent advantages, disadvantages, and success rates. Rib fracture pain management practice is founded on the thoracic surgical and anesthesiology literature. Articles addressing rib fracture pain are relatively scarce in the pain medicine literature. As life expectancy increases, and as healthcare system modifications are implemented, pain medicine physicians may be consulted to treat increasing number of patients suffering rib fracture pain and may need to resort to novel therapeutic measures because of financial constraints imposed by those changes. Here we present the first published case series of thoracic epidural steroid injections used for management of rib fracture pain. © 2012 The Authors Pain Practice © 2012 World Institute of Pain.

  7. Postamputation pain: epidemiology, mechanisms, and treatment

    Directory of Open Access Journals (Sweden)

    Hsu E

    2013-02-01

    Full Text Available Eugene Hsu,1 Steven P Cohen21Johns Hopkins School of Medicine, Baltimore, MD, USA; 2Johns Hopkins School of Medicine and Uniformed Services, University of the Health Sciences, Bethesda, MD, USAAbstract: Postamputation pain (PAP is highly prevalent after limb amputation but remains an extremely challenging pain condition to treat. A large part of its intractability stems from the myriad pathophysiological mechanisms. A state-of-art understanding of the pathophysiologic basis underlying postamputation phenomena can be broadly categorized in terms of supraspinal, spinal, and peripheral mechanisms. Supraspinal mechanisms involve somatosensory cortical reorganization of the area representing the deafferentated limb and are predominant in phantom limb pain and phantom sensations. Spinal reorganization in the dorsal horn occurs after deafferentation from a peripheral nerve injury. Peripherally, axonal nerve damage initiates inflammation, regenerative sprouting, and increased "ectopic" afferent input which is thought by many to be the predominant mechanism involved in residual limb pain or neuroma pain, but may also contribute to phantom phenomena. To optimize treatment outcomes, therapy should be individually tailored and mechanism based. Treatment modalities include injection therapy, pharmacotherapy, complementary and alternative therapy, surgical therapy, and interventions aimed at prevention. Unfortunately, there is a lack of high quality clinical trials to support most of these treatments. Most of the randomized controlled trials in PAP have evaluated medications, with a trend for short-term efficacy noted for ketamine and opioids. Evidence for peripheral injection therapy with botulinum toxin and pulsed radiofrequency for residual limb pain is limited to very small trials and case series. Mirror therapy is a safe and cost-effective alternative treatment modality for PAP. Neuromodulation using implanted motor cortex stimulation has shown a trend

  8. Low back pain - acute

    Science.gov (United States)

    Backache; Low back pain; Lumbar pain; Pain - back; Acute back pain; Back pain - new; Back pain - short-term; Back strain - new ... lower back supports most of your body's weight. Low back pain is the number two reason that Americans see ...

  9. Odontogenic keratocyst: a peripheral variant.

    Science.gov (United States)

    Vij, H; Vij, R; Gupta, V; Sengupta, S

    2011-01-01

    Odontogenic keratocyst, which is developmental in nature, is an intraosseous lesion though on rare occasions it may occur in an extraosseous location. The extraosseous variant is referred to as peripheral odontogenic keratocyst. Though, clinically, peripheral odontogenic keratocyst resembles the gingival cyst of adults, it has histologic features that are pathognomonic of odontogenic keratocyst. This article presents a case of this uncommon entity.

  10. Towards a neurobiological understanding of pain in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Søren S; Krauss, Theresa; Demir, Ihsan Ekin

    2017-01-01

    a chronic pain syndrome. Objectives: We aimed to characterize the neurobiological signature of pain associated with CP and to discuss its implications for treatment strategies. Methods: Relevant basic and clinical articles were selected for review following an extensive search of the literature. Results......: Pathophysiological changes in the peripheral (pancreatic gland) and central nervous system characterize the pain syndrome associated with CP; involved mechanisms can be broken down to 3 main branches: (1) peripheral sensitization, (2) pancreatic neuropathy, and (3) neuroplastic changes in the central pain pathways...... with those observed in neuropathic pain disorders and have important implications for treatment; adjuvant analgesics are effective in a subset of patients, and neuromodulation and neuropsychological interventions may prove useful in the future. Conclusion: Chronic pancreatitis is associated with abnormal...

  11. 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...

  12. The sources of pain in osteoarthritis: a pathophysiological review

    Directory of Open Access Journals (Sweden)

    F. Salaffi

    2014-06-01

    Full Text Available The pain of osteoarthritis (OA has multifaceted etiologies within and outside the joint. It is believed to be driven by both nociceptive and neuropathic mechanisms, as well as abnormal excitability in the pain pathways of the peripheral and central nervous system. Inflammation in the joint triggers a cascade of events that leads to peripheral sensitization, increased sensitivity of nociceptive primary afferent neurons, and hyperexcitability of the nociceptive neurons in the central nervous system. Pain receptors have been found in the synovium, ligaments, capsule, subchondral bone and surrounding tissues, with the exception of articular cartilage. The bone-related causes of pain in OA include subchondral microfractures, bone stretching with elevation of the periosteum due to osteophyte growth, bone remodeling and repair, bone marrow lesions, and bone angina caused by decreased blood flow and increased intra-osseous pressure. Central factors alter pain processing by setting the gain in such a way that, when a peripheral input is present, it is processed against a background of central factors that can enhance or diminish the experience of pain. As a complex phenomenon with a strong subjective component, pain can also be influenced by the nature of the underlying disease, personal predisposition (biological and psychological, and environmental and psychosocial factors. This review examines the current literature regarding the sources and mechanisms of pain in OA.

  13. Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats

    Science.gov (United States)

    Todorovic, Slobodan M; Rastogi, A J; Jevtovic-Todorovic, Vesna

    2003-01-01

    Anticonvulsant agents are commonly used to treat neuropathic pain conditions because of their effects on voltage- and ligand-gated channels in central pain pathways. However, their interaction with ion channels in peripheral pain pathways is poorly understood. Therefore, we studied the potential analgesic effects of commonly used anticonvulsant agents in peripheral nociception. We injected anticonvulsants intradermally into peripheral receptive fields of sensory neurons in the hindpaws of adult rats, and studied pain perception using the model of acute thermal nociception. Commonly used anticonvulsants such as voltage-gated Na+ channel blockers, phenytoin and carbamazepine, and voltage-gated Ca2+ channel blockers, gabapentin and ethosuximide, induced dose-dependent analgesia in the injected paw, with ED50 values of 0.30, 0.32 and 8, 410 μg per 100 μl, respectively. Thermal nociceptive responses were not affected in the contralateral, noninjected paws, indicating a lack of systemic effects with doses of anticonvulsants that elicited local analgesia. Hill slope coefficients for the tested anticonvulsants indicate that the dose–response curve was less steep for gabapentin than for phenytoin, carbamazepine and ethosuximide. Our data strongly suggest that cellular targets like voltage-gated Na+ and Ca2+ channels, similar to those that mediate the effects of anticonvulsant agents in the CNS, may exist in the peripheral nerve endings of rat sensory neurons. Thus, peripherally applied anticonvulsants that block voltage-gated Na+ and Ca2+ channels may be useful analgesics. PMID:12970103

  14. Painful menstrual periods

    Science.gov (United States)

    Menstruation - painful; Dysmenorrhea; Periods - painful; Cramps - menstrual; Menstrual cramps ... into two groups, depending on the cause: Primary dysmenorrhea Secondary dysmenorrhea Primary dysmenorrhea is menstrual pain that ...

  15. Alternative medicine - pain relief

    Science.gov (United States)

    Acupuncture - pain relief; Hypnosis - pain relief; Guided imagery - pain relief ... neck, shoulder, knee, or elbow) Osteoarthritis Rheumatoid arthritis Hypnosis is a focused state of concentration. With self- ...

  16. Chest pain

    International Nuclear Information System (INIS)

    Martinez A, Juan Carlos; Saenz M, Oscar; Martinez M, Camilo; Gonzales A Francisco; Nicolas R, Jose; Vergara V, Erika P; Pereira G, Alberto M

    2010-01-01

    In emergency departments, chest pain is one of the leading motives of consultation. We thus consider it important to review aspects such as its classification, causes, and clinical profiles. Initial assessment should include a full clinical history comprising thorough anamnesis and physical examination. Adequate interpretation of auxiliary tests, ordered in accordance with suspected clinical conditions, should lead to accurate diagnosis. We highlight certain symptoms and clinical signs, ECG and X-ray findings, cardiac bio markers, arterial blood gases, and CT-scanning. Scores of severity and prognosis such as TIMI are assessed. Optimal treatment of the clinical conditions leading to chest pain depends on adequate initial approach and assessment.

  17. Botulinum toxin A, brain and pain.

    Science.gov (United States)

    Matak, Ivica; Lacković, Zdravko

    2014-01-01

    Botulinum neurotoxin type A (BoNT/A) is one of the most potent toxins known and a potential biological threat. At the same time, it is among the most widely used therapeutic proteins used yearly by millions of people, especially for cosmetic purposes. Currently, its clinical use in certain types of pain is increasing, and its long-term duration of effects represents a special clinical value. Efficacy of BoNT/A in different types of pain has been found in numerous clinical trials and case reports, as well as in animal pain models. However, sites and mechanisms of BoNT/A actions involved in nociception are a matter of controversy. In analogy with well known neuroparalytic effects in peripheral cholinergic synapses, presently dominant opinion is that BoNT/A exerts pain reduction by inhibiting peripheral neurotransmitter/inflammatory mediator release from sensory nerves. On the other hand, growing number of behavioral and immunohistochemical studies demonstrated the requirement of axonal transport for BoNT/A's antinociceptive action. In addition, toxin's enzymatic activity in central sensory regions was clearly identified after its peripheral application. Apart from general pharmacology, this review summarizes the clinical and experimental evidence for BoNT/A antinociceptive activity and compares the data in favor of peripheral vs. central site and mechanism of action. Based on literature review and published results from our laboratory we propose that the hypothesis of peripheral site of BoNT/A action is not sufficient to explain the experimental data collected up to now. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Accuracy and complications of CT-guided core needle biopsy of peripheral nerve sheath tumours

    International Nuclear Information System (INIS)

    Pianta, Marcus; Chock, Eric; Schlicht, Stephen; McCombe, David

    2015-01-01

    This single-centre study retrospectively reviews the complications in patients that have occurred following peripheral nerve sheath tumour biopsy, and assesses whether there is an association with biopsy technique or underlying lesion characteristics. 41 consecutive core needle biopsies of proven peripheral nerve sheath tumours over a 2-year period in a tertiary teaching hospital were reviewed. Patient demographics and symptoms, tumour characteristics and radiological appearances were recorded. Biopsy and surgical histology were correlated, and post-biopsy and surgical complications analyzed. 41 biopsies were performed in 38 patients. 68 % schwannomas, 24 % neurofibromas and 7 % malignant peripheral nerve sheath tumours. Biopsy histology correlated with surgery in all cases. 71 % of lesions were surgically excised. 60 % of patients reported pain related to their lesion. Following the biopsy, 12 % reported increased pain, which resolved in all cases. Pain exacerbation was noted in tumours smaller in size, more superficial and in closer proximity of the biopsy needle tip to the traversing nerve. Number of biopsy needle passes was not associated with an increased incidence of procedure-related pain. Core biopsy of a suspected peripheral nerve sheath tumour may be performed safely before excisional surgery to confirm lesion histology and assist prognosis. There is excellent correlation between core biopsy and excised surgical specimen histology. The most common complication of pain exacerbation is seen in a minority and is temporary, and more likely with smaller, more superficial lesions and a closer needle-tip to traversing nerve distance during biopsy. (orig.)

  19. Accuracy and complications of CT-guided core needle biopsy of peripheral nerve sheath tumours

    Energy Technology Data Exchange (ETDEWEB)

    Pianta, Marcus; Chock, Eric; Schlicht, Stephen [St Vincent' s Hospital, Fitzroy, VIC (Australia); McCombe, David [St Vincent' s Hospital and Victorian Hand Surgery Associates, Victoria (Australia)

    2015-09-15

    This single-centre study retrospectively reviews the complications in patients that have occurred following peripheral nerve sheath tumour biopsy, and assesses whether there is an association with biopsy technique or underlying lesion characteristics. 41 consecutive core needle biopsies of proven peripheral nerve sheath tumours over a 2-year period in a tertiary teaching hospital were reviewed. Patient demographics and symptoms, tumour characteristics and radiological appearances were recorded. Biopsy and surgical histology were correlated, and post-biopsy and surgical complications analyzed. 41 biopsies were performed in 38 patients. 68 % schwannomas, 24 % neurofibromas and 7 % malignant peripheral nerve sheath tumours. Biopsy histology correlated with surgery in all cases. 71 % of lesions were surgically excised. 60 % of patients reported pain related to their lesion. Following the biopsy, 12 % reported increased pain, which resolved in all cases. Pain exacerbation was noted in tumours smaller in size, more superficial and in closer proximity of the biopsy needle tip to the traversing nerve. Number of biopsy needle passes was not associated with an increased incidence of procedure-related pain. Core biopsy of a suspected peripheral nerve sheath tumour may be performed safely before excisional surgery to confirm lesion histology and assist prognosis. There is excellent correlation between core biopsy and excised surgical specimen histology. The most common complication of pain exacerbation is seen in a minority and is temporary, and more likely with smaller, more superficial lesions and a closer needle-tip to traversing nerve distance during biopsy. (orig.)

  20. Peripheral Auditory Mechanisms

    CERN Document Server

    Hall, J; Hubbard, A; Neely, S; Tubis, A

    1986-01-01

    How weIl can we model experimental observations of the peripheral auditory system'? What theoretical predictions can we make that might be tested'? It was with these questions in mind that we organized the 1985 Mechanics of Hearing Workshop, to bring together auditory researchers to compare models with experimental observations. Tbe workshop forum was inspired by the very successful 1983 Mechanics of Hearing Workshop in Delft [1]. Boston University was chosen as the site of our meeting because of the Boston area's role as a center for hearing research in this country. We made a special effort at this meeting to attract students from around the world, because without students this field will not progress. Financial support for the workshop was provided in part by grant BNS- 8412878 from the National Science Foundation. Modeling is a traditional strategy in science and plays an important role in the scientific method. Models are the bridge between theory and experiment. Tbey test the assumptions made in experim...

  1. Pain Control After Surgery: Pain Medicines

    Science.gov (United States)

    ... Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality Birth Control Family Health Infants and Toddlers Kids and Teens ... Bracing: What Works? Home Prevention and Wellness Pain Control After Surgery: Pain Medicines Pain Control After Surgery: ...

  2. Physical Therapy in the Treatment of Central Pain Mechanisms for Female Sexual Pain.

    Science.gov (United States)

    Vandyken, Carolyn; Hilton, Sandra

    2017-01-01

    The complexity of female sexual pain requires an interdisciplinary approach. Physical therapists trained in pelvic health conditions are well positioned to be active members of an interdisciplinary team addressing the assessment and treatment of female sexual pain. Changes within physical therapy practice in the last ten years have resulted in significant utilization of pelvic floor muscle relaxation and manual therapy techniques to address a variety of pelvic pain conditions, including female sexual pain. However, sexual pain is a complex issue giving credence to the necessity of addressing all of the drivers of the pain experience- biological, psychological and social. This review aims to reconcile current pain science with a plan for integrating a biopsychosocial approach into the evaluation and subsequent treatment for female sexual pain for physical therapists. A literature review of the important components of skilled physical therapy interventions is presented including the physical examination, pain biology education, cognitive behavioral influences in treatment design, motivational interviewing as an adjunct to empathetic practice, and the integration of non-threatening movement and mindfulness into treatment. A single case study is used to demonstrate the biopsychosocial framework utilized in this approach. Appropriate measures for assessing psychosocial factors are readily available and inform a reasoned approach for physical therapy design that addresses both peripheral and central pain mechanisms. Decades of research support the integration of a biopsychosocial approach in the treatment of complex pain, including female sexual pain. It is reasonable for physical therapists to utilize evidence based strategies such as CBT, pain biology education, Mindfulness Based Stress Reduction (MBSR), yoga and imagery based exercises to address the biopsychosocial components of female sexual pain. Copyright © 2016 International Society for Sexual Medicine

  3. Breast pain

    Science.gov (United States)

    ... that reducing the amount of fat, caffeine, or chocolate in your diet helps reduce breast pain. Vitamin ... harmful, but most studies have not shown any benefit. Talk to your provider before starting any medicine or ... Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA. Review provided by ...

  4. Foot pain

    Science.gov (United States)

    ... that you were born with or develops later Injury Shoes that fit poorly or do not have much cushioning Too much walking or other sports activity Trauma The following can cause foot pain: Arthritis and gout . Common in the big toe, which becomes red, swollen, ...

  5. Pain (PDQ)

    Science.gov (United States)

    ... intravenous chemotherapy. Mucositis (sores or inflammation in the mouth or other parts of the digestive system ) caused by chemotherapy or targeted therapy. Skin pain, rash, or hand-foot syndrome (redness, tingling, or burning in the palms of the hands and/or ...

  6. Achilles Pain.

    Science.gov (United States)

    Connors, G. Patrick

    Five ailments which can cause pain in the achilles tendon area are: (1) muscular strain, involving the stretching or tearing of muscle or tendon fibers; (2) a contusion, inflammation or infection called tenosynovitis; (3) tendonitis, the inflammation of the tendon; (4) calcaneal bursitis, the inflammation of the bursa between the achilles tendon…

  7. [Social pain].

    Science.gov (United States)

    Shimoyama, Naohito; Shimoyama, Megumi

    2011-09-01

    This chapter focuses on what social pain is and how it should be managed. In order to understand social pain in a cancer patient, it is necessary to recognize the change in the patient's daily life after the diagnosis of cancer. Because the degree of suffering and the relationships with family members and the people he or she worked with differ from patient to patient, it is important to note that the context of social pain is different in each patient. Five points shown below are essential in managing social pain. 1. Economical suffering may be alleviated by utilization of the social security system while taking into account each patient's standard of living. 2. Burdens on family members should be lessened, such as by not having them stay at the patient's bedside every day and letting them go home occasionally. 3. The normal patterns of communication, support, and conflict in the family should be identified, and the extent to which they have been disrupted by the illness should be assessed. 4. It is important to understand the ethnic, cultural, and religious background of the patient and the potential impact of their influence on the individual and the illness. 5. Practical or emotional unfinished business that the patient has needs to be identified, and efforts should be made to support fulfillment.

  8. Leg pain

    Science.gov (United States)

    ... in the blood Medicines (such as diuretics and statins) Muscle fatigue or strain from overuse, too much exercise, or holding a muscle in the same position for a long time An injury can also cause leg pain from: A torn or overstretched muscle ( strain ) Hairline ...

  9. Habituating pain

    DEFF Research Database (Denmark)

    Ajslev, Jeppe Zielinski Nguyen; Lund, Henrik Lambrecht; Møller, Jeppe Lykke

    2013-01-01

    and pain as unavoidable conditions in construction work. Based on 32 semi-structured interviews performed in eight case studies within four different construction professions, workers’ descriptions of physical strain and its relation to the organizational and social context are analyzed through concepts...

  10. Orofacial pain

    Directory of Open Access Journals (Sweden)

    Marjolijn Oomens

    2016-06-01

    Full Text Available In the primary care sector, diagnosis and initial management of orofacial pain are often performed by familydoctors and dentists. Knowledge of the different types of orofacial pain and headache disorders is therefor of great importance. The International Classification of Headache Disorders (ICHD-3 provides an overview of the different types of orofacial pain and will be discussed in this lecture. The main focus will be on trigeminal neuralgia and cluster headache and the current research in this field. Trigeminal Neuralgia (TN is defined as a disorder characterized by recurrent, unilateral, brief, electricshock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of thetrigeminal nerve and triggered by innocuous stimuli. Unfortunately, most TN is idiopathic, and the aetiology isnot clear. The guidelines on pharmaceutical TN management published by the American Academy of Neurology (AAN and the European Federation of Neurological Societies (EFNS recommend carbamazepine (CBZ; 200–1200 mg/day or oxcarbazepine (OXC; 600–1800 mg/day as first-line therapy. Both are antiepileptics with well known interactions with other drugs and safety problems. An overview of the currently available literature on the pharmaceutical management of TN patients is discussed. Cluster headache (CH is one of the most painful primary headache disorders. It is characterized by daily or almost daily attacks of unilateral excruciating periorbital pain associated with ipsilateral cranial autonomic symptoms, typically lasting between 15 and 180 minutes if untreated. Cluster headache is caused by the relaesement of neurotransmitters and vasodilators from the sphenopalatine ganglion (SPH. The SPG is a large extracranial parasympathetic ganglion located in the pterygopalatine fossa (PPF. The current treatments for CH attacks are injectable sumatriptan and oxygen inhalation. Both treatments have well known side effects and

  11. "Real-life" treatment of chronic pain: Targets and goals.

    Science.gov (United States)

    Ablin, Jacob N; Buskila, Dan

    2015-02-01

    Treating chronic pain is a complex challenge. While textbooks and medical education classically categorize pain as originating from peripheral (nociceptive), neuropathic, or centralized origins, in real life each and every patient may present a combination of various pain sources, types, and mechanisms. Moreover, individual patients may evolve and develop differing types of pain throughout their clinical follow-up, further emphasizing the necessity to maintain clinical diligence during the evaluation and follow-up of these patients. Rational treatment of patients suffering from chronic pain must attempt at deconstructing complex pain cases, identifying variegate pain generators, and targeting them with appropriate interventions, while incorporating both pharmacological and non-pharmacological strategies, rather than focusing on the total pain level, which represents an integral of all pain types. Failing to recognize the coexistence of different types of pain in an individual patient and escalating medications only on the basis of total pain intensity are liable to lead to both ineffective control of pain and increased untoward effects. In the current review, we outline strategies for deconstructing complex pain and therapeutic suggestions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Neurobiological and clinical relationship between psychiatric disorders and chronic pain.

    Science.gov (United States)

    Bras, Marijana; Dordević, Veljko; Gregurek, Rudolf; Bulajić, Masa

    2010-06-01

    Pain is one of the most ubiquitous problems of today's world, its impact being far-reaching. Current conceptualizations of pain medicine adopt a bio-psycho-social perspective. In this model, pain is best described as an interactive, psycho-physiological behavioral pattern that cannot be divided into independent psycho-social and physical components. Neurophysiologic substrates of the pain experience can be broken down into the pain transmission elements emanating from peripheral, spinal, and supra-spinal processes. There are many complex mechanisms involved in pain processing within the central nervous system, being influenced by genetics, interaction of neurotransmitters and their receptors, and pain- augmenting and pain-inhibiting neural circuits. The patient's emotional experiences, beliefs and expectations may determine the outcome of treatment, and are fully emphasized in the focus of treatment interventions. There are several common psychiatric disorders accompanying and complicating the experience of pain that warrant clinical attention and that can be the focus of psychiatric treatment. These include depression, anxiety, sleep disorders, somatoform disorders, substance-related disorders and personality disorders. Complex and disabling pain conditions often require comprehensive pain treatment programs, involving interdisciplinary and multimodal treatment approaches. There are many roles that the psychiatrist can perform in the assessment and treatment of the patients with pain, individually tailored to meet the specific needs of the patient. Rational poly-pharmacy is of a high importance in the treatment of patients with chronic pain, with antidepressants and anticonvulsants contributing as the important adjuvant analgesic agents.

  13. The Neurobiology of Orofacial Pain and Sleep and Their Interactions.

    Science.gov (United States)

    Lavigne, G J; Sessle, B J

    2016-09-01

    This article provides an overview of the neurobiology of orofacial pain as well as the neural processes underlying sleep, with a particular focus on the mechanisms that underlie pain and sleep interactions including sleep disorders. Acute pain is part of a hypervigilance system that alerts the individual to injury or potential injury of tissues. It can also disturb sleep. Disrupted sleep is often associated with chronic pain states, including those that occur in the orofacial region. The article presents many insights that have been gained in the last few decades into the peripheral and central mechanisms involved in orofacial pain and its modulation, as well as the circuits and processes in the central nervous system that underlie sleep. Although it has become clear that sleep is essential to preserve and maintain health, it has also been found that pain, particularly chronic pain, is commonly associated with disturbed sleep. In the presence of chronic pain, a circular relationship may prevail, with mutual deleterious influences causing an increase in pain and a disruption of sleep. This article also reviews findings that indicate that reducing orofacial pain and improving sleep need to be targeted together in the management of acute to chronic orofacial pain states in order to improve an orofacial pain patient's quality of life, to prevent mood alterations or exacerbation of sleep disorder (e.g., insomnia, sleep-disordered breathing) that can negatively affect their pain, and to promote healing and optimize their health. © International & American Associations for Dental Research 2016.

  14. When Sex Is Painful

    Science.gov (United States)

    ... AQ FREQUENTLY ASKED QUESTIONS GYNECOLOGIC PROBLEMS FAQ020 When Sex Is Painful • How common is painful sex? • What causes pain during sex? • Where is pain during sex felt? • When should ...

  15. Pain Information Brochure

    Science.gov (United States)

    ... Library Health Care Systems Research Collaboratory Pain Registries IOM Report: Relieving Pain in America HHS Pathways to ... Library Health Care Systems Research Collaboratory Pain Registries IOM Report: Relieving Pain in America HHS Pathways to ...

  16. NIH Pain Consortium

    Science.gov (United States)

    ... Library Health Care Systems Research Collaboratory Pain Registries IOM Report: Relieving Pain in America HHS Pathways to ... Library Health Care Systems Research Collaboratory Pain Registries IOM Report: Relieving Pain in America HHS Pathways to ...

  17. Back pain and sports

    Science.gov (United States)

    ... Running - back pain; Weightlifting - back pain; Lumbar pain - sports; Sciatica - sports; Low back pain - sports ... MD, Thompson SR, eds. DeLee and Drez's Orthopaedic Sports Medicine: Principles and Practice . 4th ed. Philadelphia, PA: ...

  18. Back Pain During Pregnancy

    Science.gov (United States)

    ... Advocacy For Patients About ACOG Back Pain During Pregnancy Home For Patients Search FAQs Back Pain During ... FAQ115, January 2016 PDF Format Back Pain During Pregnancy Pregnancy What causes back pain during pregnancy? How ...

  19. Virtual visual reminiscing pain stimulation of allodynia patients activates cortical representation of pain and emotions. fMRI study

    International Nuclear Information System (INIS)

    Ikemoto, Tatsunori; Ushida, Takahiro; Taniguchi, Shinichirou; Tania, Toshikazu; Zinchuk, V.; Morio, Kazuo; Sasaki, Toshikazu

    2004-01-01

    It is widely known that sensation of the pain is derived from sensory-discriminative factor and emotional factor. Especially in chronic pain, emotional factors and psychosocial backgrounds are more likely to contribute for the patients' discomfort. The aim of this study is to investigate how emotional factor of pain participates in intractable pain. We employed functional MRI (fMRI) to compare the brain activations occurring in the orthopaedic neuropathic pain patients with allodynia and normal individuals in response to the visual virtual painful experience. During fMRI scanning, a video demonstrating an actual tactile stimulation of the palm and its imitation were shown to participants. In contrast to normal individuals, allodynia patients also displayed activation of the areas reflecting emotions: frontal lobe and anterior cingulate. These findings suggest that brain have important role in the development and maintaining of peripheral originated chronic painful condition. (author)

  20. Whole-body vibration as a modality for the rehabilitation of peripheral neuropathies: implications for cancer survivors suffering from chemotherapy-induced peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Anna L.J. Verhulst

    2015-02-01

    Full Text Available The objective was to study the effect of whole-body vibration (WBV on strength, balance and pain in patients with peripheral neuropathies and to consider its significance for the rehabilitation of patients suffering from chemotherapy-induced peripheral neuropathy (CIPN. Using a broad search strategy, PubMed was searched for clinical trials on WBV interventions aimed at improving strength, balance or pain in patients with peripheral neuropathies, which were published in English until 5th June 2014. The search was performed by the first author and generated a total of 505 results, which yielded 5 articles that met the inclusion criteria, being studies: i published in English; ii involving adult human subjects’ peripheral neuropathies; iii evaluating the effect of WBV as a therapeutic intervention; and iv reporting findings for at least one of the following outcomes: strength, balance or pain. Methodological quality of included studies was assessed independently by first and second author, using the physiotherapy evidence database scale. The overall methodological quality of included studies was low. Two studies found a beneficial effect of WBV on neuropathic pain, but another study failed to find the same effect. One study found significant improvements in both muscle strength and balance, while another study found improvements only in some, but not all, of the applied tests to measure muscle strength and balance. The results of this literature search suggest insufficient evidence to assess the effectiveness for the effects of WBV on neuropathic pain, muscle strength and balance in patients with peripheral neuropathies. More high-quality trials are needed to guide the optimization of rehabilitation programs for cancer survivors with CIPN in particular.

  1. Nonlinear dimension reduction and clustering by Minimum Curvilinearity unfold neuropathic pain and tissue embryological classes

    KAUST Repository

    Cannistraci, Carlo; Ravasi, Timothy; Montevecchi, Franco Maria; Ideker, Trey; Alessio, Massimo

    2010-01-01

    algorithms, MCE and MCAP, whether individually or combined in H2P, overcome the limits of classical approaches. High performance was attained in the visualization and classification of: (i) pain patients (proteomic measurements) in peripheral neuropathy; (ii

  2. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  3. Network node for peripheral sharing

    International Nuclear Information System (INIS)

    Bobbitt, J.; Johnson, M.

    1977-01-01

    A module which enables several independent computer systems to share the peripherals (graphics display and line printer) of a PDP-11 computer is described. The module requires no software support in the PDP-11

  4. Deep brain stimulation for phantom limb pain.

    Science.gov (United States)

    Bittar, Richard G; Otero, Sofia; Carter, Helen; Aziz, Tipu Z

    2005-05-01

    Phantom limb pain is an often severe and debilitating phenomenon that has been reported in up to 85% of amputees. Its pathophysiology is poorly understood. Peripheral and spinal mechanisms are thought to play a role in pain modulation in affected individuals; however central mechanisms are also likely to be of importance. The neuromatrix theory postulates a genetically determined representation of body image, which is modified by sensory input to create a neurosignature. Persistence of the neurosignature may be responsible for painless phantom limb sensations, whereas phantom limb pain may be due to abnormal reorganisation within the neuromatrix. This study assessed the clinical outcome of deep brain stimulation of the periventricular grey matter and somatosensory thalamus for the relief of chronic neuropathic pain associated with phantom limb in three patients. These patients were assessed preoperatively and at 3 month intervals postoperatively. Self-rated visual analogue scale pain scores assessed pain intensity, and the McGill Pain Questionnaire assessed the quality of the pain. Quality of life was assessed using the EUROQOL EQ-5D scale. Periventricular gray stimulation alone was optimal in two patients, whilst a combination of periventricular gray and thalamic stimulation produced the greatest degree of relief in one patient. At follow-up (mean 13.3 months) the intensity of pain was reduced by 62% (range 55-70%). In all three patients, the burning component of the pain was completely alleviated. Opiate intake was reduced in the two patients requiring morphine sulphate pre-operatively. Quality of life measures indicated a statistically significant improvement. This data supports the role for deep brain stimulation in patients with phantom limb pain. The medical literature relating to the epidemiology, pathogenesis, and treatment of this clinical entity is reviewed in detail.

  5. Biopsychosocial Profiles and Functional Correlates in Older Adults with Chronic Low Back Pain: A Preliminary Study.

    Science.gov (United States)

    Weiner, Debra K; Gentili, Angela; Coffey-Vega, Katherine; Morone, Natalia; Rossi, Michelle; Perera, Subashan

    2018-04-16

    To describe key peripheral and central nervous system (CNS) conditions in a group of older adults with chronic low back pain (CLBP) and their association with pain severity and self-reported and performance-based physical function. Cross-sectional. Outpatient VA clinics. Forty-seven community-dwelling veterans with CLBP (age 68.0 ± 6.5 years, range = 60-88 years, 12.8% female, 66% white) participated. Data were collected on peripheral pain generators-body mass index, American College of Rheumatology hip osteoarthritis criteria, neurogenic claudication (i.e., spinal stenosis), sacroiliac joint (SIJ) pain, myofascial pain, leg length discrepancy (LLD), and iliotibial band pain; and CNS pain generators-anxiety (GAD-7), depression (PHQ-9), insomnia (Insomnia Severity Index), maladaptive coping (Fear Avoidance Beliefs Questionnaire, Cognitive Strategies Questionnaire), and fibromyalgia (fibromyalgia survey). Outcomes were pain severity (0 to 10 scale, seven-day average and worst), self-reported pain interference (Roland Morris [RM] questionnaire), and gait speed. Approximately 96% had at least one peripheral CLBP contributor, 83% had at least one CNS contributor, and 80.9% had both peripheral and CNS contributors. Of the peripheral conditions, only SIJ pain and LLD were associated with outcomes. All of the CNS conditions and SIJ pain were related to RM score. Only depression/anxiety and LLD were associated with gait speed. In this sample of older veterans, CLBP was a multifaceted condition. Both CNS and peripheral conditions were associated with self-reported and performance-based function. Additional investigation is required to determine the impact of treating these conditions on patient outcomes and health care utilization.

  6. Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Annett Eitner

    2017-11-01

    Full Text Available Pain due to osteoarthritis (OA is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate

  7. Transforaminal epidural steroid injections influence Mechanical Diagnosis and Therapy (MDT) pain response classification in candidates for lumbar herniated disc surgery.

    Science.gov (United States)

    van Helvoirt, Hans; Apeldoorn, Adri T; Knol, Dirk L; Arts, Mark P; Kamper, Steven J; van Tulder, Maurits W; Ostelo, Raymond W

    2016-04-27

    Prospective cohort study. Although lumbar radiculopathy is regarded as a specific diagnosis, the most effective treatment strategy is unclear. Commonly used treatments include transforaminal epidural steroid injections (TESIs) and Mechanical Diagnosis & Therapy (MDT), but no studies have investigated the effectiveness of this combination. MDT differentiates pain centralization (C) from non-centralization (NC), which indicates good vs. poor prognostic validity respectively. The main aims were 1) to determine changes in Mechanical Diagnosis and Therapy (MDT) pain response classifications after transforaminal epidural steroid injections (TESIs) in candidates for lumbar herniated disc surgery and 2) to evaluate differences in short and long term outcomes for patients with different pain response classifications. Candidates for lumbar herniated disc surgery were assessed with a MDT protocol and their pain response classified as centralizing or peripheralizing. For this study,only patients were eligible who showed a peripheralizing pain response at intake. All patients then received TESIs and were reassessed and classified using the MDT protocol, into groups according to pain response (resolved, centralizing, peripheralizing with less pain and peripheralising with severe pain). After receiving targeted treatment based on pain response after TESIs, ranging from advice, MDT or surgery, follow-up assessments were completed at discharge and at 12 months. The primary outcomes were disability (Roland-Morris Disability Questionnaire [RMDQ] for Sciatica), pain severity in leg (visual analogue scale [VAS], 0-100) and global perceived effect (GPE). Linear mixed-models were used to determine between-groups differences in outcome. A total of 77 patients with lumbar disc herniation and peripheralizing symptoms were included. Patients received an average of 2 (SD 0.7) TESIs. After TESIs, 17 patients (22%) were classified as peripheralizing with continuing severe pain.These patients

  8. The Role of Purinergic Receptors in Cancer-Induced Bone Pain

    Directory of Open Access Journals (Sweden)

    Sarah Falk

    2012-01-01

    Full Text Available Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord. Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of purinergic receptors in cancer-induced bone pain with emphasis on some of the difficulties related to studying this complex pain state.

  9. Is the Experience of Thermal Pain Genetics Dependent?

    Directory of Open Access Journals (Sweden)

    Emilia Horjales-Araujo

    2015-01-01

    Full Text Available It is suggested that genetic variations explain a significant portion of the variability in pain perception; therefore, increased understanding of pain-related genetic influences may identify new targets for therapies and treatments. The relative contribution of the different genes to the variance in clinical and experimental pain responses remains unknown. It is suggested that the genetic contributions to pain perception vary across pain modalities. For example, it has been suggested that more than 60% of the variance in cold pressor responses can be explained by genetic factors; in comparison, only 26% of the variance in heat pain responses is explained by these variations. Thus, the selection of pain model might markedly influence the magnitude of the association between the pain phenotype and genetic variability. Thermal pain sensation is complex with multiple molecular and cellular mechanisms operating alone and in combination within the peripheral and central nervous system. It is thus highly probable that the thermal pain experience is affected by genetic variants in one or more of the pathways involved in the thermal pain signaling. This review aims to present and discuss some of the genetic variations that have previously been associated with different experimental thermal pain models.

  10. Cortical plasticity as a new endpoint measurement for chronic pain

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2011-07-01

    Full Text Available Abstract Animal models of chronic pain are widely used to investigate basic mechanisms of chronic pain and to evaluate potential novel drugs for treating chronic pain. Among the different criteria used to measure chronic pain, behavioral responses are commonly used as the end point measurements. However, not all chronic pain conditions can be easily measured by behavioral responses such as the headache, phantom pain and pain related to spinal cord injury. Here I propose that cortical indexes, that indicate neuronal plastic changes in pain-related cortical areas, can be used as endpoint measurements for chronic pain. Such cortical indexes are not only useful for those chronic pain conditions where a suitable animal model is lacking, but also serve as additional screening methods for potential drugs to treat chronic pain in humans. These cortical indexes are activity-dependent immediate early genes, electrophysiological identified plastic changes and biochemical assays of signaling proteins. It can be used to evaluate novel analgesic compounds that may act at peripheral or spinal sites. I hope that these new cortical endpoint measurements will facilitate our search for new, and more effective, pain medicines, and help to reduce false lead drug targets.

  11. 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.

  12. Duloxetine Contributing to a Successful Multimodal Treatment Program for Peripheral Femoral Neuropathy and Comorbid ‘Reactive Depression’ in an Adolescent

    OpenAIRE

    Kachko, Ludmyla; Ben Ami, Shiri; Liberman, Alon; Birk, Einat; Kronenberg, Sefi

    2011-01-01

    In the United States, duloxetine has been approved for the treatment of major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia in the adult population. Data regarding the use of duloxetine in the pediatric population, however, are very limited. Femoral nerve injury is a rare complication of cardiac catheterization. In the case described, duloxetine contributed to a successful multimodal treatment program for peripheral neuropathic pain due to femoral neuropathy in an...

  13. Induction and modulation of referred muscle pain in humans

    DEFF Research Database (Denmark)

    Laursen, René Johannes

    correlated to pain intensity, and LP and RP thresholds were reproducible within and between sessions. Experimentally (electrical stimulation and infusion of hypertonic saline) induced muscle pain seems to be mediated by myelinated and unmyelinated afferents and the peripheral component of RP by myelinated...... afferents. Furthermore, cutaneous anesthesia of the RP area resulted in a reduction of RP intensity of 22%, while a complete nerve block of afferents from the RP area resulted in a 40% reduction. In summary, observations from the presented experiments suggest that elicitation of referred muscle pain...... is depending on and correlated to local muscle pain. Peripheral input from the RP area is involved, but is not a necessary condition for RP to appear. The present studies as well as others suggest that central hyperexcitability is involved in the generation of RP, but further investigations on mechanisms of RP...

  14. Nociception and role of immune system in pain.

    Science.gov (United States)

    Verma, Vivek; Sheikh, Zeeshan; Ahmed, Ahad S

    2015-09-01

    Both pain and inflammation are protective responses. However, these self-limiting conditions (with well-established negative feedback loops) become pathological if left uncontrolled. Both pain and inflammation can interact with each other in a multi-dimensional manner. These interactions are known to create an array of 'difficult to manage' pathologies. This review explains in detail the role of immune system and the related cells in peripheral sensitization and neurogenic inflammation. Various neuro-immune interactions are analyzed at peripheral, sensory and central nervous system levels. Innate immunity plays a critical role in central sensitization and in establishing acute pain as chronic condition. Moreover, inflammatory mediators also exhibit psychological effects, thus contributing towards the emotional elements associated with pain. However, there is also a considerable anti-inflammatory and analgesic role of immune system. This review also attempts to enlist various novel pharmacological approaches that exhibit their actions through modification of neuro-immune interface.

  15. Peripheral arterial tonometry cannot detect patients at low risk of coronary artery disease

    NARCIS (Netherlands)

    M.M. van den Heuvel (Mieke); O. Sorop (Oana); P. Musters (Paul); R.T. van Domburg (Ron); T.W. Galema (Tjebbe); D.J.G.M. Duncker (Dirk); W.J. van der Giessen (Wim); K. Nieman (Koen)

    2015-01-01

    textabstractBackground Endothelial dysfunction precedes coronary artery disease (CAD) and can be measured by peripheral arterial tonometry (PAT). We examined the applicability of PAT to detect a low risk of CAD in a chest pain clinic. Methods In 93 patients, PAT was performed resulting in reactive

  16. Mechanisms and management of functional abdominal pain.

    Science.gov (United States)

    Farmer, Adam D; Aziz, Qasim

    2014-09-01

    Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory systems may have an important role. The management of patients with functional abdominal pain requires a tailored multidisciplinary approach in a supportive and empathetic environment in order to develop an effective therapeutic relationship. Patient education directed towards an explanation of the pathophysiology of functional abdominal pain is in our opinion a prerequisite step and provides the rationale for the introduction of interventions. Interventions can usefully be categorised into general measures, pharmacotherapy, psychological interventions and 'step-up' treatments. Pharmacotherapeutic/step-up options include tricyclic antidepressants, serotonin noradrenergic reuptake inhibitors and the gabapentinoids. Psychological treatments include cognitive behavioural therapy and hypnotherapy. However, the objective evidence base for these interventions is largely derived from other chronic pain syndrome, and further research is warranted in adult patients with functional abdominal pain. © The Royal Society of Medicine.

  17. Approach to Peripheral Neuropathy for the Primary Care Clinician.

    Science.gov (United States)

    Doughty, Christopher T; Seyedsadjadi, Reza

    2018-02-02

    Peripheral neuropathy is commonly encountered in the primary care setting and is associated with significant morbidity, including neuropathic pain, falls, and disability. The clinical presentation of neuropathy is diverse, with possible symptoms including weakness, sensory abnormalities, and autonomic dysfunction. Accordingly, the primary care clinician must be comfortable using the neurologic examination-including the assessment of motor function, multiple sensory modalities, and deep tendon reflexes-to recognize and characterize neuropathy. Although the causes of peripheral neuropathy are numerous and diverse, careful review of the medical and family history coupled with limited, select laboratory testing can often efficiently lead to an etiologic diagnosis. This review offers an approach for evaluating suspected neuropathy in the primary care setting. It will describe the most common causes, suggest an evidence-based workup to aid in diagnosis, and highlight recent evidence that allows for selection of symptomatic treatment of patients with neuropathy. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Investigating Circadian Rhythmicity in Pain Sensitivity Using a Neural Circuit Model for Spinal Cord Processing of Pain

    DEFF Research Database (Denmark)

    Crodelle, Jennifer; Piltz, Sofia Helena; Booth, Victoria

    2017-01-01

    Primary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating the resu......Primary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating...... the resultant pain signal. The differential equation models describe the average firing rates of excitatory and inhibitory interneuron populations, as well as the wide dynamic range (WDR) neurons whose output correlates with the pain signal. The temporal profile of inputs on the different afferent nerve fibers...

  19. Effect of levetiracetam on the postmastectomy pain syndrome

    DEFF Research Database (Denmark)

    Vilholm, O J; Cold, S; Rasmussen, L

    2008-01-01

    BACKGROUND AND PURPOSE: The aim of this randomized, double-blind, placebo-controlled, cross-over study was to test whether levetiracetam relieves the postmastectomy pain syndrome (PMPS). METHODS: Postmastectomy pain syndrome was defined as pain of neuropathic character located in the area...... of the surgery and/or the ipsilateral arm. The inclusion criteria were: age more than 18 years, characteristic symptoms corresponding to PMPS more than 6 months after surgery for breast cancer, pain duration more than 3 months, peripheral nerve lesions confirmed by abnormal neurological and quantitative sensory...... tests, intensity of pain more than 4 on a numeric rating scale from 0 to 10 and pain present at least 4 days a week. RESULTS: Forty-nine patients were screened for participation and 27 patients were included in the study. Twenty-five patients completed two treatment phases of 4 weeks duration...

  20. Scratching the surface: the processing of pain from deep tissues.

    Science.gov (United States)

    Sikandar, Shafaq; Aasvang, Eske Kvanner; Dickenson, Anthony H

    2016-04-01

    Although most pain research focuses on skin, muscles, joints and viscerae are major sources of pain. We discuss the mechanisms of deep pains arising from somatic and visceral structures and how this can lead to widespread manifestations and chronification. We include how both altered peripheral and central sensory neurotransmission lead to deep pain states and comment on key areas such as top-down modulation where little is known. It is vital that the clinical characterization of deep pain in patients is improved to allow for back translation to preclinical models so that the missing links can be ascertained. The contribution of deeper somatic and visceral tissues to various chronic pain syndromes is common but there is much we need to know.

  1. Pain and the ethics of pain management.

    Science.gov (United States)

    Edwards, R B

    1984-01-01

    In this article I clarify the concepts of 'pain', 'suffering', 'pains of body', 'pains of soul'. I explore the relevance of an ethic to the clinical setting which gives patients a strong prima facie right to freedom from unnecessary and unwanted pain and which places upon medical professionals two concomitant moral obligations to patients. First, there is the duty not to inflict pain and suffering beyond what is necessary for effective diagnosis, treatment and research. Next, there is the duty to do all that can be done to relieve all the pain and suffering which can be alleviated. I develop in some detail that individuality of pain sensitivity must be taken into account in fulfilling these obligations. I explore the issue of the relevance of informed consent and the right to refuse treatment to the matter of pain relief. And I raise the question of what conditions, if any, should override the right to refuse treatment where pain relief is of paramount concern.

  2. Peripheral nerve conduits: technology update

    Science.gov (United States)

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  3. Paediatric pain management

    African Journals Online (AJOL)

    patients is musculoskeletal pain, headache or abdominal pain.2. The pain ... Children older than four years of age can usually talk about their pain; at the age of six to eight years they can use the ... Pain presentation in children normally falls into one of the ... expression, body posture and movement.10 This scale is often.

  4. Pain and Nociception

    DEFF Research Database (Denmark)

    Falk, Sarah; Dickenson, Anthony H

    2014-01-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditiona...

  5. 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

  6. Modulation of oral heat and cold pain by irritant chemicals.

    Science.gov (United States)

    Albin, Kelly C; Carstens, Mirela Iodi; Carstens, E

    2008-01-01

    Common food irritants elicit oral heat or cool sensations via actions at thermosensitive transient receptor potential (TRP) channels. We used a half-tongue, 2-alternative forced-choice procedure coupled with bilateral pain intensity ratings to investigate irritant effects on heat and cold pain. The method was validated in a bilateral thermal difference detection task. Capsaicin, mustard oil, and cinnamaldehyde enhanced lingual heat pain elicited by a 49 degrees C stimulus. Mustard oil and cinnamaldehyde weakly enhanced lingual cold pain (9.5 degrees C), whereas capsaicin had no effect. Menthol significantly enhanced cold pain and weakly reduced heat pain. To address if capsaicin's effect was due to summation of perceptually similar thermal and chemical sensations, one-half of the tongue was desensitized by application of capsaicin. Upon reapplication, capsaicin elicited little or no irritant sensation yet still significantly enhanced heat pain on the capsaicin-treated side, ruling out summation. In a third experiment, capsaicin significantly enhanced pain ratings to graded heat stimuli (47 degrees C to 50 degrees C) resulting in an upward shift of the stimulus-response function. Menthol may induce cold hyperalgesia via enhanced thermal gating of TRPM8 in peripheral fibers. Capsaicin, mustard oil, and cinnamaldehyde may induce heat hyperalgesia via enhanced thermal gating of TRPV1 that is coexpressed with TRPA1 in peripheral nociceptors.

  7. Transvenous sclerotherapy of peripheral arteriovenous malformations and hemangiomas

    International Nuclear Information System (INIS)

    Hunter, D.W.; Moradian, G.P.; Castaneda-Zuniga, W.R.; Amplantz, K.

    1989-01-01

    After exsanguination of the lesion and control of arterial inflow and venous outflow, the authors used a transvenous or direct puncture technique for injection of a sclerosing solution (3% sotradecol and ionic contrast material) to treat 18 patients with peripheral arteriovenous malformations or hemangiomas. The results are discussed. Good results were achieved in 12 patients. The other six patients had residual symptoms. Multiple treatment sessions were usually necessary. Short-term management included the use of intravenous heparin, steroids, and antibiotics. No significant long-term complications occurred. Short-term complications, including swelling, local pain, blistering, and localized deep venous thrombosis, occurred in 70% of the patients

  8. Peripheral nervous system involvement in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    P. R. Kamchatnov

    2016-01-01

    Full Text Available Diabetes mellitus is a widespread disease often affecting peripheral nervous system. This include diabetic autonomous neuropathy that can endanger the patient's life. Timely detection of complications of diabetes mellitus as well as its adequate therapy can improve prognosis of the disease. The possibilities of Milgamma and Tiogamma for pathogenic therapy in patients with diabetic polyneuropathy are considered in this paper. Gabagamma can be effectively relieve neuropathic pain and used together with other drugs that normalize nerve tissue metabolism.

  9. Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain

    Directory of Open Access Journals (Sweden)

    Yul Huh

    2017-08-01

    Full Text Available Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain, and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL-1β, IL-6, CCL2, and CXCL1]. Recent studies suggest that bone marrow stem cells or bone marrow stromal cells (BMSCs produce powerful analgesic effects in animal models of inflammatory pain, neuropathic pain, and cancer pain. We recently demonstrated that intrathecal injection of BMSCs resulted in a long-term relief of neuropathic pain for several weeks after peripheral nerve injury. Strikingly, this analgesic effect is mediated by the anti-inflammatory cytokine transforming growth factor beta secreted from BMSCs. Additionally, BMSCs exhibit potent modulation of neuroinflammation, by inhibiting monocyte infiltration, glial activation, and cytokine/chemokine production in the DRG and spinal cord. Thus, BMSCs control chronic pain by regulation of neuroinflammation in the PNS and CNS via paracrine signaling. In this review, we discuss the similar results from different laboratories of remarkable anti-nociceptive efficacy of BMSCs in animal and clinical studies. We also discuss the mechanisms by which BMSCs control neuroinflammation and chronic pain and how these cells specifically migrate to damaged tissues.

  10. Spinal cord stimulation: Current applications for treatment of chronic pain.

    Science.gov (United States)

    Vannemreddy, Prasad; Slavin, Konstantin V

    2011-01-01

    Spinal cord stimulation (SCS) is thought to relieve chronic intractable pain by stimulating nerve fibers in the spinal cord. The resulting impulses in the fibers may inhibit the conduction of pain signals to the brain, according to the pain gate theory proposed by Melzack and Wall in 1965 and the sensation of pain is thus blocked. Although SCS may reduce pain, it will not eliminate it. After a period of concern about safety and efficacy, SCS is now regaining popularity among pain specialists for the treatment of chronic pain. The sympatholytic effect of SCS is one of its most interesting therapeutic properties. This effect is considered responsible for the effectiveness of SCS in peripheral ischemia, and at least some cases of complex regional pain syndrome. The sympatholytic effect has also been considered part of the management of other chronic pain states such as failed back surgery syndrome, phantom pain, diabetic neuropathy, and postherpetic neuralgia. In general, SCS is part of an overall treatment strategy and is used only after the more conservative treatments have failed. The concept of SCS has evolved rapidly following the technological advances that have produced leads with multiple contact electrodes and battery systems. The current prevalence of patients with chronic pain requiring treatment other than conventional medical management has significantly increased and so has been the need for SCS. With the cost benefit analysis showing significant support for SCS, it may be appropriate to offer this as an effective alternative treatment for these patients.

  11. Effects of neonatal pain, stress and their interrelation on pain sensitivity in later life in male rats.

    Science.gov (United States)

    Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Aloisi, Anna Maria

    2016-08-31

    Neonatal pain and stress induce long-term changes in pain sensitivity. Therefore their interrelation is a topical subject of clinical and basic research. The present study investigated the effects of inflammatory peripheral pain and stress of maternal deprivation (MD)-isolation in 1-2- and 7-8-day-old Wistar rats (P1,2 and P7,8 respectively, ages comparable to preterm and full-term human babies) on basal pain and pain sensitivity in conditions of inflammatory pain (formalin test) during adolescence. The neonatal impacts were: pain (formalin injection, FOR in the paw), stress (a short 60-min MD), or pain+stress combination (FOR+MD), and appropriate controls. We found that stress of short-term maternal deprivation-isolation and inflammatory pain on P1,2 and P7,8 significantly increased the vulnerability of the nociceptive system to inflammatory pain. Maternal deprivation-isolation on P1,2 as compared with a similar impact on P7,8 had a greater effect on pain sensitivity of the adolescent rats, but the influence of early pain was independent of the injury age. Only adolescent rats with an early combination of pain and maternal deprivation-isolation showed hypoalgesia in the hot plate (HP) test. However licking duration (reflecting pain sensitivity) in these rats did not exceed licking duration in animals exposed only to maternal deprivation-isolation or pain. This study adds new data to the growing body of work demonstrating that early noxious impacts have long-term consequences for the functional activity of the nociceptive system. Our new findings may help to understand the impact of pain and maternal separation in the neonatal intensive care unit.

  12. Peripheral Atherectomy: Applications and Techniques.

    Science.gov (United States)

    Mittleider, Derek; Russell, Erich

    2016-06-01

    Peripheral atherectomy is a class of procedures that is rapidly increasing in volume. Multiple classes of devices exist, and newer variants are added to the market annually. The devices see wide application for de novo lesions, in-stent restenosis, and adjunctive therapy for drug-coated balloons. The body of evidence supporting atherectomy is less robust than for many other peripheral therapies. The frequency and severity of complications from atherectomy can be significant compared with angioplasty and stenting, and familiarity with preventative and bailout techniques is essential for the interventionalist. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. [Atherectomy for peripheral arterial disease].

    Science.gov (United States)

    Londero, Louise Skovgaard; Høgh, Annette Langager; Lindholt, Jes Sanddal

    2015-04-13

    Symptomatic peripheral arterial disease is managed according to national and international guidelines and the number of vascular reconstructions performed each year has increased over the past decade mainly due to an increasing frequency of endovascular procedures. Atherectomy as an alternative to the established treatment of symptomatic peripheral arterial disease has recently been analysed in a Cochrane review. In Denmark, atherectomy is not performed and so far the evidence is poor as the method is not an alternative to the established treatment in this country.

  14. Imaging of the peripheral retina

    Directory of Open Access Journals (Sweden)

    Marcus Kernt

    2013-01-01

    Full Text Available The technical progress of the recent years has revolutionized imaging in ophthalmology. Scanning laser ophthalmoscopy (SLO, digital angiography, optical coherence tomography (OCT, and detection of fundus autofluorescence (FAF have fundamentally changed our understanding of numerous retinal and choroidal diseases. Besides the tremendous advances in macular diagnostics, there is more and more evidence that central pathologies are often directly linked to changes in the peripheral retina. This review provides a brief overview on current posterior segment imaging techniques with a special focus on the peripheral retina.

  15. Screening for Peripheral Artery Disease

    Science.gov (United States)

    ... pressure. The ultrasound machine is based on a concept first put forth by a scientist named Christian ... treadmill walking rehabilitation program. A Food and Drug Administration–approved medication, cilostazol, may improve pain-free walking ...

  16. Evidence for local inflammation in complex regional pain syndrome type 1

    Directory of Open Access Journals (Sweden)

    Frank J. P. M. Huygen

    2002-01-01

    Full Text Available Background: The pathophysiology of complex regional pain syndrome type 1 (CRPS 1 is still a matter of debate. Peripheral afferent, efferent and central mechanisms are supposed. Based on clinical signs and symptoms (e.g. oedema, local temperature changes and chronic pain local inflammation is suspected.

  17. [Characteristics of pain syndrome in patients with upper limbs occupational polyneuropathies].

    Science.gov (United States)

    Kochetova, O A; Mal'kova, N Yu

    2015-01-01

    Pain syndrome accompanies various diseases of central and peripheral nervous system--that is one of the most important problems in contemporary neurology. Many scientists are in search for effective diagnostic and therapeutic tools. The article covers characteristics of the pain syndrome and its mechanisms in patients with upper limbs occupational polyneuropathies.

  18. Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy

    NARCIS (Netherlands)

    de Vos, C.; de Vos, Cecile C.; Rajan, Vinayakrishnan; Steenbergen, Wiendelt; van der Aa, Hans E.; Buschman, H.P.J.

    2009-01-01

    Aim: Spinal cord stimulation (SCS) has been shown effective as a therapy for different chronic painful conditions, but the effectiveness of this treatment for pain as a result of peripheral diabetic neuropathy is not well established. The primary objectives of this study were to evaluate the effect

  19. Spinal cord stimulation in patients with painful diabetic neuropathy: A multicentre randomized clinical trial

    NARCIS (Netherlands)

    de Vos, Cecilia Cecilia Clementine; Meier, Kaare; Brocades Zaalberg, Paul; Nijhuis, Harold J.A.; Duyvendak, Wim; Vesper, Jan; Enggaard, Thomas P.; Lenders, Mathieu W.P.M.

    2014-01-01

    Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our

  20. Generalized and symptom-specific sensitization of chronic itch and pain.

    NARCIS (Netherlands)

    Laarhoven, A.I.M. van; Kraaimaat, F.W.; Wilder-Smith, O.H.G.; Kerkhof, P.C.M. van de; Cats, H.; Riel, P.L.C.M. van; Evers, A.W.M.

    2007-01-01

    BACKGROUND: Physicians are frequently confronted with patients reporting severe itch and pain. Particularly in patients suffering from persistent itch and pain, central and peripheral sensitization processes are assumed to be involved in the long-term maintenance and aggravation of the symptoms. The

  1. Contribution of the local and referred pain from active myofascial trigger points in fibromyalgia syndrome

    DEFF Research Database (Denmark)

    Ge, Hong-You; Nie, Hongling; Madeleine, Pascal

    2009-01-01

    The generalized hypersensitivity associated with fibromyalgia syndrome (FMS) may in part be driven by peripheral nociceptive sources. The aim of the study was to investigate whether local and referred pain from active myofascial trigger points (MTrPs) contributes to fibromyalgia pain. FMS patients...

  2. Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors.

    Science.gov (United States)

    Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J

    Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition.

  3. specific low back pain

    African Journals Online (AJOL)

    2015-09-01

    Sep 1, 2015 ... SPECIFIC LOW BACK PAIN: IMPLICATION FOR DIRECT HEALTH. CARE COST ... abundant evidence suggesting the benefits of therapeu- tic exercise on pain and ... Exercise and behavioural therapies in chronic pain. 174.

  4. Low back pain - chronic

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007422.htm Low back pain - chronic To use the sharing features on this page, please enable JavaScript. Low back pain refers to pain that you feel in your ...

  5. Palliative care - managing pain

    Science.gov (United States)

    ... page, please enable JavaScript. Palliative care is a holistic approach to care that focuses on treating pain ... stressful for you and your family. But with treatment, pain can be managed. How Pain is Measured ...

  6. Side Effects: Pain

    Science.gov (United States)

    Controlling pain is an important part of your cancer treatment plan. Learn how to track levels of pain. Find out how pain, a side effect of cancer treatment, is treated using acupuncture, biofeedback, and physical therapy.

  7. Neuro Emotional Technique for the treatment of trigger point sensitivity in chronic neck pain sufferers: A controlled clinical trial

    OpenAIRE

    Bablis, Peter; Pollard, Henry; Bonello, Rod

    2008-01-01

    Abstract Background Trigger points have been shown to be active in many myofascial pain syndromes. Treatment of trigger point pain and dysfunction may be explained through the mechanisms of central and peripheral paradigms. This study aimed to investigate whether the mind/body treatment of Neuro Emotional Technique (NET) could significantly relieve pain sensitivity of trigger points presenting in a cohort of chronic neck pain sufferers. Methods Sixty participants presenting to a private chiro...

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

    Directory of Open Access Journals (Sweden)

    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

  9. Soul Pain

    Directory of Open Access Journals (Sweden)

    Sarah L. Jirek

    2015-07-01

    Full Text Available This study extends prior research on vicarious traumatization and emotion management by exploring a deeper, more life-altering effect of working with traumatized clients—namely, “soul pain.” Analyses of in-depth interviews with 29 advocates working with survivors of physical and sexual violence reveal that, as a direct consequence of hearing countless stories of human brutality, some staff members experience a profound wounding of their spirit. This finding expands our understanding of the occupational hazards of the helping professions by revealing another dimension of advocates’ lives—that of the soul or spirit—that may be affected by their work with trauma survivors.

  10. Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins.

    Science.gov (United States)

    Tian, Jinge; Yu, Tingting; Xu, Yongming; Pu, Shaofeng; Lv, Yingying; Zhang, Xin; DU, Dongping

    2018-01-01

    Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT.

  11. Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves

    Directory of Open Access Journals (Sweden)

    Steven M. Horton

    2017-11-01

    Full Text Available The pannexin family of channels consists of three members—pannexin-1 (Panx1, pannexin-2 (Panx2, and pannexin-3 (Panx3 that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system and PNS (peripheral nervous system, coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.

  12. Procedural pain in neonatal units in Kenya.

    Science.gov (United States)

    Kyololo, O'Brien Munyao; Stevens, Bonnie; Gastaldo, Denise; Gisore, Peter

    2014-11-01

    To determine the nature and frequency of painful procedures and procedural pain management practices in neonatal units in Kenya. Cross-sectional survey. Level I and level II neonatal units in Kenya. Ninety-five term and preterm neonates from seven neonatal units. Medical records of neonates admitted for at least 24 h were reviewed to determine the nature and frequency of painful procedures performed in the 24 h period preceding data collection (6:00 to 6:00) as well as the pain management interventions (eg, morphine, breastfeeding, skin-to-skin contact, containment, non-nutritive sucking) that accompanied each procedure. Neonates experienced a total of 404 painful procedures over a 24 h period (mean=4.3, SD 2.0; range 1-12); 270 tissue-damaging (mean=2.85, SD 1.1; range 1-6) and 134 non-tissue-damaging procedures (mean=1.41, SD 1.2; range 0-6). Peripheral cannula insertion (27%) and intramuscular injections (22%) were the most common painful procedures. Ventilated neonates and neonates admitted in level II neonatal units had a higher number of painful procedures than those admitted in level I units (mean 4.76 vs 2.96). Only one procedure had a pain intensity score documented; and none had been performed with any form of analgesia. Neonates in Kenya were exposed to numerous tissue-damaging and non-tissue-damaging procedures without any form of analgesia. Our findings suggest that education is needed on how to assess and manage procedural pain in neonatal units in Kenya. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Neuropathic pain-like alterations in muscle nociceptor function associated with vibration-induced muscle pain.

    Science.gov (United States)

    Chen, Xiaojie; Green, Paul G; Levine, Jon D

    2010-11-01

    We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ∼15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ∼44Hz during a 1min suprathreshold stimulus) much greater than that has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration-exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  14. 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...

  15. Peripheral facial weakness (Bell's palsy).

    Science.gov (United States)

    Basić-Kes, Vanja; Dobrota, Vesna Dermanović; Cesarik, Marijan; Matovina, Lucija Zadro; Madzar, Zrinko; Zavoreo, Iris; Demarin, Vida

    2013-06-01

    Peripheral facial weakness is a facial nerve damage that results in muscle weakness on one side of the face. It may be idiopathic (Bell's palsy) or may have a detectable cause. Almost 80% of peripheral facial weakness cases are primary and the rest of them are secondary. The most frequent causes of secondary peripheral facial weakness are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immune disorders, drugs, degenerative diseases of the central nervous system, etc. The diagnosis relies upon the presence of typical signs and symptoms, blood chemistry tests, cerebrospinal fluid investigations, nerve conduction studies and neuroimaging methods (cerebral MRI, x-ray of the skull and mastoid). Treatment of secondary peripheral facial weakness is based on therapy for the underlying disorder, unlike the treatment of Bell's palsy that is controversial due to the lack of large, randomized, controlled, prospective studies. There are some indications that steroids or antiviral agents are beneficial but there are also studies that show no beneficial effect. Additional treatments include eye protection, physiotherapy, acupuncture, botulinum toxin, or surgery. Bell's palsy has a benign prognosis with complete recovery in about 80% of patients, 15% experience some mode of permanent nerve damage and severe consequences remain in 5% of patients.

  16. MEGACARYOCYTES IN THE PERIPHERAL CIRCULATION

    Science.gov (United States)

    Minot, George R.

    1922-01-01

    A megacaryocyte is seen commonly as an occasional cell in the peripheral blood of patients with myelogenous leucemia. Less commonly they appear in relatively large numbers. These giant cells also may occur in the blood under other conditions. Their presence is indicative of a bone marrow under intense strain. PMID:19868650

  17. [Ultrasound-guided peripheral catheterization].

    Science.gov (United States)

    Salleras-Duran, Laia; Fuentes-Pumarola, Concepció

    2016-01-01

    Peripheral catheterization is a technique that can be difficult in some patients. Some studies have recently described the use of ultrasound to guide the venous catheterization. To describe the success rate, time required, complications of ultrasound-guided peripheral venous catheterization. and patients and professionals satisfaction The search was performed in databases (Medline-PubMed, Cochrane Library, CINAHL and Cuiden Plus) for studies published about ultrasound-guided peripheral venous catheterization performed on patients that provided results on the success of the technique, complications, time used, patient satisfaction and the type of professional who performed the technique. A total of 21 studies were included. Most of them get a higher success rate 80% in the catheterization ecoguide and time it is not higher than the traditional technique. The Technical complications analyzed were arterial puncture rates and lower nerve 10%. In all studies measuring and comparing patient satisfaction in the art ecoguide is greater. Various professional groups perform the technique. The use of ultrasound for peripheral pipes has a high success rate, complications are rare and the time used is similar to that of the traditional technique. The technique of inserting catheters through ultrasound may be learned by any professional group performing venipuncture. Finally, it gets underscores the high patient satisfaction with the use of this technique. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  18. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...

  19. What Is Peripheral Artery Disease?

    Science.gov (United States)

    ... or bluish color to the skin A lower temperature in one leg compared to the other leg Poor nail growth on the toes and decreased hair growth on the legs Erectile dysfunction, especially among men who have diabetes Diagnosis Peripheral artery disease (P.A.D.) is diagnosed based ...

  20. Inguinal hernia repair: anaesthesia, pain and convalescence

    DEFF Research Database (Denmark)

    Callesen, Torben

    2003-01-01

    of less serious complications is lower by local anaesthesia, compared to other anaesthetic techniques. Of special interest is, that the rate of urinary retention can be eliminated by the use of local anaesthesia. Local anaesthesia results, in comparative studies, in a higher degree of patient satisfaction...... than other anaesthetic techniques. Local anaesthesia also facilitates faster mobilisation and earlier discharge/fulfilment of discharge criteria from post anaesthetic care units than other anaesthetic techniques. Pain after hernia repair is more pronounced at mobilisation or coughing than during rest....... Pain after laparoscopic surgery is less pronounced than after open surgery, while different open repair techniques do not exhibit significant differences. Postoperative pain is best treated with a combination of local analgesia and peripherally acting agents (paracetamol, NSAID or their combination...

  1. Optogenetic exploration and modulation of pain processing.

    Science.gov (United States)

    Xie, Yu-Feng; Wang, Jing; Bonin, Robert P

    2018-08-01

    Intractable pain is the single most common cause of disability, affecting more than 20% of the population world-wide. There is accordingly a global effort to decipher how changes in nociceptive processing in the peripheral and central nervous systems contribute to the onset and maintenance of chronic pain. The past several years have brought rapid progress in the adaptation of optogenetic approaches to study and manipulate the activity of sensory afferents and spinal cord neurons in freely behaving animals, and to investigate cortical processing and modulation of pain responses. This review discusses methodological advances that underlie this recent progress, and discusses practical considerations for the optogenetic modulation of nociceptive sensory processing. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  2. Expression changes of microRNA-1 and its targets Connexin 43 and brain-derived neurotrophic factor in the peripheral nervous system of chronic neuropathic rats

    NARCIS (Netherlands)

    Neumann, Elena; Hermanns, Henning; Barthel, Franziska; Werdehausen, Robert; Brandenburger, Timo

    2015-01-01

    MicroRNAs (miRNAs) are involved in the neuroplastic changes which induce and maintain neuropathic pain. However, it is unknown whether nerve injury leads to altered miRNA expression and modulation of pain relevant target gene expression within peripheral nerves. In the present study, expression

  3. PET-scan shows peripherally increased neurokinin 1 receptor availability in chronic tennis elbow: visualizing neurogenic inflammation?

    Directory of Open Access Journals (Sweden)

    Magnus Peterson

    Full Text Available In response to pain, neurokinin 1 (NK1 receptor availability is altered in the central nervous system. The NK1 receptor and its primary agonist, substance P, also play a crucial role in peripheral tissue in response to pain, as part of neurogenic inflammation. However, little is known about alterations in NK1 receptor availability in peripheral tissue in chronic pain conditions and very few studies have been performed on human beings. Ten subjects with chronic tennis elbow were therefore examined by positron emission tomography (PET with the NK1 specific radioligand [(11C]GR205171 before and after treatment with graded exercise. The radioligand signal intensity was higher in the affected arm as compared with the unaffected arm, measured as differences between the arms in volume of voxels and signal intensity of this volume above a reference threshold set as 2.5 SD above mean signal intensity of the unaffected arm before treatment. In the eight subjects examined after treatment, pain ratings decreased in all subjects but signal intensity decreased in five and increased in three. In conclusion, NK1 receptors may be activated, or up-regulated in the peripheral, painful tissue of a chronic pain condition. This up-regulation does, however, have moderate correlation to pain ratings. The increased NK1 receptor availability is interpreted as part of ongoing neurogenic inflammation and may have correlation to the pathogenesis of chronic tennis elbow.ClinicalTrials.gov NCT00888225 http://clinicaltrials.gov/

  4. Central Pain Syndrome

    Science.gov (United States)

    ... such as neurontin (gabapentin) can be useful. Lowering stress levels appears to reduce pain. View Full Treatment Information Definition Central pain syndrome is a neurological condition caused ...

  5. When pain after surgery doesn't go away...

    LENUS (Irish Health Repository)

    Burke, Siún

    2009-02-01

    Chronic post-surgical pain is a common, under-recognized and important clinical problem which affects millions of patients worldwide. It results from a series of neuroplastic changes associated most commonly with peripheral nerve injury at the time of surgery. Predisposing factors include the type of surgery, pre-operative and acute post-operative pain intensity, and probably psychological (e.g. pain-catastrophizing) and genetic factors [e.g. GCH1 (GTP cyclohydrolase 1) haplotype]. Preventive measures which are currently available include selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen. Very promising therapeutic agents which target the sensitization process are currently in development.

  6. Spinal cord stimulation therapy for localized central pain

    International Nuclear Information System (INIS)

    Hirato, Masafumi; Takahashi, Akio; Watanabe, Katsushige; Kazama, Ken; Yoshimoto, Yuhei

    2008-01-01

    We studied the pathophysiology of localized central pain and the surgical result of spinal cord stimulation. There were 10 cases; 7 males and 3 females from 24 to 77 years old. Pain was caused by peripheral nerve injury in one case, spinal cord injury in two cases and cerebrovascular disease (CVD) (thalamic pain) in 7 cases. All cases were treated by epidural spinal cord stimulation and followed from 0.8 to 8.8 years. Sufficient pain relief was achieved in one case of peripheral nerve and spinal cord injury and in 4 cases of CVD. Moderate pain control was achieved in 2 cases of CVD. In one each case of spinal cord injury and of CVD, pain control was ineffective. In cases with thalamic pain, we studied the correlation between the surgical result of spinal cord stimulation and the clinical features, MRI, fluoro-deoxyglucose (FDG)-positron emission tomography (PET), and somatosensory evoked potentials (SEP) findings before operation. MRI revealed a small to moderate sized lesion on the thalamus or putamen in each case. PET also showed decreased accumulation of FDG on the affected thalamus. In all cases without one fair responder to spinal cord stimulation, we could recognize definite SEP originating in the sensory cortex ipsilateral side to the CVD lesion during contralateral median or posterior tibial nerve stimulation. In the good responders, we could recognize SEP originating in the sensory cortex of the lesion side with less delayed latency or decreased amplitude than in the moderate responders. In this group, test stimulation with low voltage on the spinal cord evoked a sensory effect (paresthesia) over the painful part of the body. Spinal cord stimulation proved to be an effective treatment for localized central pain. In cases with localized central pain after CVD, we could expect to ameliorate the intractable pain in those cases in which SEP or spinal cord test stimulation revealed that the thalamo-cortical system was preserved. (author)

  7. Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

    OpenAIRE

    Chen, Longtu; Ilham, Sheikh J.; Feng, Bin

    2017-01-01

    Context Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also...

  8. 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-...

  9. Abnormal muscle afferent function in a model of Taxol chemotherapy-induced painful neuropathy

    OpenAIRE

    Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

    2011-01-01

    Despite muscle pain being a well-described symptom in patients with diverse forms of peripheral neuropathy, the role of neuropathic mechanisms in muscle pain have received remarkably little attention. We have recently demonstrated in a well-established model of chemotherapy-induced painful neuropathy (CIPN) that the anti-tumor drug paclitaxel (Taxol) produces mechanical hyperalgesia in skeletal muscle, of similar time course to and with shared mechanism with cutaneous symptoms. In the present...

  10. Pain in Fabry Disease: Practical Recommendations for Diagnosis and Treatment.

    Science.gov (United States)

    Politei, Juan M; Bouhassira, Didier; Germain, Dominique P; Goizet, Cyril; Guerrero-Sola, Antonio; Hilz, Max J; Hutton, Elspeth J; Karaa, Amel; Liguori, Rocco; Üçeyler, Nurcan; Zeltzer, Lonnie K; Burlina, Alessandro

    2016-07-01

    Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications. © 2016 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

  11. Pain and Function Following Revision Cubital Tunnel Surgery.

    Science.gov (United States)

    Davidge, Kristen M; Ebersole, Gregory C; Mackinnon, Susan E

    2017-11-01

    The purpose of this study was to determine pain and functional outcomes following revision cubital tunnel surgery and to identify predictors of poor postoperative outcome. A retrospective cohort study was conducted of all patients undergoing revision cubital tunnel surgery over a 5-year period at a high-volume peripheral nerve center. Intraoperative findings, demographic and injury factors, and outcomes were reviewed. Average pain, worst pain, and impact of pain on self-perceived quality of life were each measured using a 10-cm visual analog scale (VAS). Function was evaluated using pinch and grip strength, as well as the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Differences in preoperative and postoperative pain, strength, and DASH were analyzed using nonparametric tests. Predictors of postoperative average pain were evaluated using odds ratios and linear regression analyses. The final cohort consisted of 50 patients (mean age: 46.3 ± 12.5 years; 29 [68%] male) undergoing 52 revision ulnar nerve transpositions (UNTs). Pain VAS scores decreased significantly following revision UNT. Strength and DASH scores demonstrated nonsignificant improvements postoperatively. Worse preoperative pain and greater than 1 prior cubital tunnel procedure were significant predictors of worse postoperative average pain VAS scores. Patients can and do improve following revision cubital tunnel surgery, particularly as it relates to pain. Intraoperative findings during the revision procedure suggest that adherence to specific principles in the primary operation is key to prevention of secondary cubital tunnel syndrome.

  12. Correlation of physical factors with musculoskeletal pain among physiotherapists

    Directory of Open Access Journals (Sweden)

    Vidhi Rajen Kalyani

    2017-01-01

    Full Text Available Introduction: The etiology of musculoskeletal work related disorders remains largely unclear, pain being the predominant complaint. The prevalence of neck pain, shoulder pain, upper and lower back pain increases drastically during professional practice in Physiotherapy. This study evaluated the prevalence of musculoskeletal pain. Also, the study determined the role of modifiable risk factors for physiotherapists (physical activity, psychological status and quantity and quality of sleep for pain. Method: The study population includes 60 physiotherapists with atleast work experience of 1 year and work duration of 6 hours per day. Outcome measures used were Nordic Musculoskeletal Questionnaire as a screening tool, Orebro Musculoskeletal Pain Questionnaire, The Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH, University of Cambridge sleep questionnaire and Internet Mental Health Quality of Life (IMHQOL scale. Results: Comparatively, pain was more concentrated at spinal regions than peripheral locations among physiotherapists. Surprisingly, many physiotherapists reported multiple sites of musculoskeletal pains. Conclusion: A weak correlation was established between physical activity and musculoskeletal pain among physiotherapists.

  13. Angioplasty and stent placement - peripheral arteries - discharge

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000234.htm Angioplasty and stent placement - peripheral arteries - discharge To use the sharing ... peripheral artery). You may have also had a stent placed. To perform the procedure: Your doctor inserted ...

  14. Hypothyroidism: Can It Cause Peripheral Neuropathy?

    Science.gov (United States)

    Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...

  15. 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

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

    Science.gov (United States)

    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.

  17. The Modified painDETECT Questionnaire for Patients with Hip or Knee Osteoarthritis : Translation into Dutch, Cross-Cultural Adaptation and Reliability Assessment

    NARCIS (Netherlands)

    Rienstra, Wietske; Blikman, Tim; Mensink, Frans B.; van Raay, Jos J. A. M.; Dijkstra, Baukje; Bulstra, Sjoerd K.; Stevens, Martin; van den Akker-Scheek, Inge

    2015-01-01

    There is a growing amount of evidence that alteration in pain processing by the peripheral and central nervous system play a role in osteoarthritis pain, leading to neuropathic-like symptoms. It is essential to identify knee and hip osteoarthritis patients with a neuropathic pain profile in order to

  18. Atypical Odontalgia (Phantom Tooth Pain)

    Science.gov (United States)

    ... atypical facial pain, phantom tooth pain, or neuropathic orofacial pain, is characterized by chronic pain in a tooth ... such as a specialist in oral medicine or orofacial pain. The information contained in this monograph is for ...

  19. Molecular Mechanisms That Contribute to Bone Marrow Pain

    Directory of Open Access Journals (Sweden)

    Jason J. Ivanusic

    2017-09-01

    Full Text Available Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors. Nerve growth factor (NGF sequestration has been trialed for the management of inflammatory bone pain (osteoarthritis, and there is significant evidence for interaction of NGF with bone marrow nociceptors. Activation of transient receptor potential cation channel subfamily V member 1 sensitizes bone marrow nociceptors and could contribute to increased sensitivity of patients to noxious stimuli in various bony pathologies. Acid-sensing ion channels sense changes to tissue pH in the bone marrow microenvironment and could be targeted to treat pathology that involves acidosis of the bone marrow. Piezo2 is a mechanically gated ion channel that has recently been reported to be expressed by most myelinated bone marrow nociceptors and might be a target for treatments directed against mechanically induced bone pain. These ion channels and receptors could be useful targets for the development of peripherally acting drugs to treat pain of bony origin.

  20. Coaching Peripheral Vision Training for Soccer Athletes

    Science.gov (United States)

    Marques, Nelson Kautzner, Jr.

    2010-01-01

    Brazilian Soccer began developing its current emphasis on peripheral vision in the late 1950s, by initiative of coach of the Canto do Rio Football Club, in Niteroi, Rio de Janeiro, a pioneer in the development of peripheral vision training in soccer players. Peripheral vision training gained world relevance when a young talent from Canto do Rio,…

  1. Peripheral Neuropathy – Clinical and Electrophysiological Considerations

    Science.gov (United States)

    Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

    2013-01-01

    This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

  2. Guidelines in the management of diabetic nerve pain clinical utility of pregabalin

    Directory of Open Access Journals (Sweden)

    Vinik AI

    2013-02-01

    Full Text Available Aaron I Vinik, Carolina M Casellini Strelitz Diabetes Center for Endocrine and Metabolic Disorders, Eastern Virginia Medical School, Norfolk, VA, USA Abstract: Diabetic peripheral neuropathy is a common complication of diabetes. It presents as a variety of syndromes for which there is no universally accepted unique classification. Sensorimotor polyneuropathy is the most common type, affecting about 30% of diabetic patients in hospital care and 25% of those in the community. Pain is the reason for 40% of patient visits in a primary care setting, and about 20% of these have had pain for greater than 6 months. Chronic pain may be nociceptive, which occurs as a result of disease or damage to tissue with no abnormality in the nervous system. In contrast, neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” Persistent neuropathic pain interferes significantly with quality of life, impairing sleep and recreation; it also significantly impacts emotional well-being, and is associated with depression, anxiety, and noncompliance with treatment. Painful diabetic peripheral neuropathy is a difficult-to-manage clinical problem, and patients with this condition are more apt to seek medical attention than those with other types of diabetic neuropathy. Early recognition of psychological problems is critical to the management of pain, and physicians need to go beyond the management of pain per se if they are to achieve success. This evidence-based review of the assessment of the patient with pain in diabetes addresses the state-of-the-art management of pain, recognizing all the conditions that produce pain in diabetes and the evidence in support of a variety of treatments currently available. A search of the full Medline database for the last 10 years was conducted in August 2012 using the terms painful diabetic peripheral neuropathy, painful diabetic peripheral polyneuropathy

  3. Investigation of depression in Greek patients with diabetic peripheral neuropathy.

    Science.gov (United States)

    Rekleiti, Maria; Sarafis, Pavlos; Saridi, Maria; Toska, Aikaterini; Melos, Chrysovaladis; Souliotis, Kyriakos; Tsironi, Maria

    2013-06-16

    Considerable studies directly connect the complications in diabetic patients, and especially peripheral neuropathy, with the emergence of depression. Neuropathetic pain may deteriorate the general health status of the diabetic patient and glycaemic regulation. The purpose of this study was to investigate the appearance and degree of diabetic peripheral neuropathy and its correlation with depression, with other parameters of the disease and also duration. 57 diabetic patients participated with diagnosed diabetic peripheral neuropathy (male n=27, female n= 30, mean of age 72.7±6.35 years). The first part of Michigan Neuropathy Screening Instrument and the Zung Depression Rating Scale were used as tools for our study. Data was analysed with the SPSS 18.0 statistic program. 57.9% of the patients were overweight, 35.1% were obese and only 7% were within normal weight range. The BMI findings between the two genders indicate that male participants are more often obese than females. Women surpassed men in the category of overweight patients (p depression, it derives that a high degree of diabetic neuropathy is related with high score of depression [F(3.160)=9.821, p=0.001]. Moderate and severe neuropathy was found with almost the same levels of depression. The correlation between diabetic neuropathy and depression is confirmed, while a very high depression rate was found in patients with severe neuropathy. The issue needs further study by using common instruments to obtain comparative results from the scientific community.

  4. Peripheral Glial Cells in the Development of Diabetic Neuropathy

    Science.gov (United States)

    Gonçalves, Nádia Pereira; Vægter, Christian Bjerggaard; Pallesen, Lone Tjener

    2018-01-01

    The global prevalence of diabetes is rapidly increasing, affecting more than half a billion individuals within the next few years. As diabetes negatively affects several physiological systems, this dramatic increase represents not only impaired quality of life on the individual level but also a huge socioeconomic challenge. One of the physiological consequences affecting up to half of diabetic patients is the progressive deterioration of the peripheral nervous system, resulting in spontaneous pain and eventually loss of sensory function, motor weakness, and organ dysfunctions. Despite intense research on the consequences of hyperglycemia on nerve functions, the biological mechanisms underlying diabetic neuropathy are still largely unknown, and treatment options lacking. Research has mainly focused directly on the neuronal component, presumably from the perspective that this is the functional signal-transmitting unit of the nerve. However, it is noteworthy that each single peripheral sensory neuron is intimately associated with numerous glial cells; the neuronal soma is completely enclosed by satellite glial cells and the length of the longest axons covered by at least 1,000 Schwann cells. The glial cells are vital for the neuron, but very little is still known about these cells in general and especially how they respond to diabetes in terms of altered neuronal support. We will discuss current knowledge of peripheral glial cells and argue that increased research in these cells is imperative for a better understanding of the mechanisms underlying diabetic neuropathy. PMID:29770116

  5. Peripheral neuropathy in prediabetes and the metabolic syndrome.

    Science.gov (United States)

    Stino, Amro M; Smith, Albert G

    2017-09-01

    Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. Most patients with non-diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle-based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  6. Imaging-guided hyperstimulation analgesia in low back pain

    Directory of Open Access Journals (Sweden)

    Gorenberg M

    2013-06-01

    Full Text Available Miguel Gorenberg,1,2 Kobi Schwartz31Department of Nuclear Medicine, B'nai Zion Medical Center, Haifa, Israel; 2The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; 3Department of Physical Therapy, B'nai Zion Medical Center, Haifa, IsraelAbstract: Low back pain in patients with myofascial pain syndrome is characterized by painful active myofascial trigger points (ATPs in muscles. This article reviews a novel, noninvasive modality that combines simultaneous imaging and treatment, thus taking advantage of the electrodermal information available from imaged ATPs to deliver localized neurostimulation, to stimulate peripheral nerve endings (Aδ fibers and in turn, to release endogenous endorphins. "Hyperstimulation analgesia" with localized, intense, low-rate electrical pulses applied to painful ATPs was found to be effective in 95% patients with chronic nonspecific low back pain, in a clinical validation study.Keywords: myofascial, noninvasive, electrical, impedance

  7. Supporting Self-management of Chronic Pain

    Science.gov (United States)

    2018-04-04

    Chronic Pain Syndrome; Chronic Pain; Chronic Pain Due to Injury; Chronic Pain Due to Trauma; Chronic Pain Due to Malignancy (Finding); Chronic Pain Post-Procedural; Chronic Pain Hip; Chronic Pain, Widespread

  8. Monitoring sweep in peripheral waterflood

    International Nuclear Information System (INIS)

    Rouser, B.J.; Al-Askar, Y.A.; Hassoun, T.H.

    1991-01-01

    This paper examines the techniques used and the results obtained in monitoring the water advance in a peripheral waterflood of a carbonate reservoir. The peripheral pattern used in the subject reservoir gives a water advanced similar to that obtained in a water drive reservoir. However, monitoring this particular reservoir is complicated by the use of a low salinity brine for flooding and the areal shape of the reservoir. The use of pulsed neutron capture logging in conjunction with production logging has been effective in differentiating between oil and water in porous zones in existing producers. The use of the two logs has been successful despite the problems normally encountered when logging open hole completions in a reservoir being flooded with a low salinity brine. Results have been confirmed and enhanced by open hole logs of new wells being drilled in the water invaded areas

  9. Paediatric pain management

    African Journals Online (AJOL)

    REVIEW. Introduction. Pain is defined by the International Association for the Study of. Pain (IASP) as ... lasts for a short time, whilst chronic pain normally persists for a much longer ..... on a regular time schedule, i.e. 'by the clock', whereby the medicine is .... combination with a non-opioid (from the first step) for severe pain.

  10. Chest Pain: First Aid

    Science.gov (United States)

    First aid Chest pain: First aid Chest pain: First aid By Mayo Clinic Staff Causes of chest pain can vary from minor problems, such as indigestion ... 26, 2018 Original article: http://www.mayoclinic.org/first-aid/first-aid-chest-pain/basics/ART-20056705 . Mayo ...

  11. Chronic pelvic pain.

    Science.gov (United States)

    Stein, Sharon L

    2013-12-01

    Chronic pelvic pain is pain lasting longer than 6 months and is estimated to occur in 15% of women. Causes of pelvic pain include disorders of gynecologic, urologic, gastroenterologic, and musculoskeletal systems. The multidisciplinary nature of chronic pelvic pain may complicate diagnosis and treatment. Treatments vary by cause but may include medicinal, neuroablative, and surgical treatments. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Peripheral nerve conduits: technology update

    Directory of Open Access Journals (Sweden)

    Arslantunali D

    2014-12-01

    Full Text Available D Arslantunali,1–3,* T Dursun,1,2,* D Yucel,1,4,5 N Hasirci,1,2,6 V Hasirci,1,2,7 1BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University (METU, Ankara, Turkey; 2Department of Biotechnology, METU, Ankara, Turkey; 3Department of Bioengineering, Gumushane University, Gumushane, Turkey; 4Faculty of Engineering, Department of Medical Engineering, Acibadem University, Istanbul, Turkey; 5School of Medicine, Department of Histology and Embryology, Acibadem University, Istanbul, Turkey; 6Department of Chemistry, Faculty of Arts and Sciences, METU, Ankara, Turkey; 7Department of Biological Sciences, Faculty of Arts and Sciences, METU, Ankara, Turkey *These authors have contributed equally to this work Abstract: Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers and designs (tubular, fibrous, and matrix type are being presented. Keywords: peripheral nerve injury, natural biomaterials, synthetic biomaterials

  13. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    LM, de Crombrugghe B. Some recent advances in the chemistry and biology of trans- forming growth factor-beta. J Cell Biol 1987;105:1039e45. 12. Hao Y...SUPPLEMENTARY NOTES 14. ABSTRACT In current war trauma, 20-30% of all extremity injuries and >80% of penetrating injuries being associated with peripheral nerve...through both axonal advance and in revascularization of the graft following placement. We are confident that this technology may allow us to

  14. Communication, Consumption and Peripheral Politics

    Directory of Open Access Journals (Sweden)

    NÍZIA VILLAÇA

    2009-02-01

    Full Text Available This essay analyses central/peripheral dynamics and its new semantics in the big scenario of globalization. The processes of hybridization between the local and the global spaces are discussed focusing the strategies of inclusion and exclusion through some examples from media and cultural industry. The methodology helps to reflect about the theme using elements of epistemology communication, consumer society and cultural studies.

  15. Pain, emotion, headache.

    Science.gov (United States)

    Bussone, Gennaro; Grazzi, Licia; Panerai, Alberto E

    2012-10-01

    Pain has been considered as part of a defensive strategy whose specific role is to signal an immediate active danger to the organism. This definition fits well for acute pain. It does not work well, however, for chronic pain that is maintained even in absence of an ongoing, active threat. Currently, acute and chronic pain are considered to be separate conditions. What follows is a review of the different theories about pain and its history. Different hypotheses regarding pain mechanisms are illustrated. New data emerging from scientific research on chronic pain (migraine in particular) involving innovative imaging techniques are reported and discussed. © 2012 American Headache Society.

  16. Peripheral facial palsy in children.

    Science.gov (United States)

    Yılmaz, Unsal; Cubukçu, Duygu; Yılmaz, Tuba Sevim; Akıncı, Gülçin; Ozcan, Muazzez; Güzel, Orkide

    2014-11-01

    The aim of this study is to evaluate the types and clinical characteristics of peripheral facial palsy in children. The hospital charts of children diagnosed with peripheral facial palsy were reviewed retrospectively. A total of 81 children (42 female and 39 male) with a mean age of 9.2 ± 4.3 years were included in the study. Causes of facial palsy were 65 (80.2%) idiopathic (Bell palsy) facial palsy, 9 (11.1%) otitis media/mastoiditis, and tumor, trauma, congenital facial palsy, chickenpox, Melkersson-Rosenthal syndrome, enlarged lymph nodes, and familial Mediterranean fever (each 1; 1.2%). Five (6.1%) patients had recurrent attacks. In patients with Bell palsy, female/male and right/left ratios were 36/29 and 35/30, respectively. Of them, 31 (47.7%) had a history of preceding infection. The overall rate of complete recovery was 98.4%. A wide variety of disorders can present with peripheral facial palsy in children. Therefore, careful investigation and differential diagnosis is essential. © The Author(s) 2013.

  17. Cancer Pain Physiology

    DEFF Research Database (Denmark)

    Falk, Sarah; Bannister, Kirsty; Dickenson, Anthony

    2014-01-01

    Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells....... This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined...... to the mouse femur. This model prompted related approaches and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer induced bone pain results in progressive bone destruction, elevated osteoclast activity...

  18. A modern neuroscience approach to chronic spinal pain: combining pain neuroscience education with cognition-targeted motor control training.

    Science.gov (United States)

    Nijs, Jo; Meeus, Mira; Cagnie, Barbara; Roussel, Nathalie A; Dolphens, Mieke; Van Oosterwijck, Jessica; Danneels, Lieven

    2014-05-01

    Chronic spinal pain (CSP) is a severely disabling disorder, including nontraumatic chronic low back and neck pain, failed back surgery, and chronic whiplash-associated disorders. Much of the current therapy is focused on input mechanisms (treating peripheral elements such as muscles and joints) and output mechanisms (addressing motor control), while there is less attention to processing (central) mechanisms. In addition to the compelling evidence for impaired motor control of spinal muscles in patients with CSP, there is increasing evidence that central mechanisms (ie, hyperexcitability of the central nervous system and brain abnormalities) play a role in CSP. Hence, treatments for CSP should address not only peripheral dysfunctions but also the brain. Therefore, a modern neuroscience approach, comprising therapeutic pain neuroscience education followed by cognition-targeted motor control training, is proposed. This perspective article explains why and how such an approach to CSP can be applied in physical therapist practice.

  19. Multidisciplinary pain management programs.

    OpenAIRE

    Kaiser, Ulrike; Arnold, Bernhard; Pfingsten, Michael; Nagel, Bernd; Lutz, Johannes; Sabatowski, Rainer

    2013-01-01

    Ulrike Kaiser,1 Bernhard Arnold,2 Michael Pfingsten,3 Bernd Nagel,4 Johannes Lutz,5 Rainer Sabatowski1,61Comprehensive Pain Center, University Hospital “Carl Gustav Carus”, Dresden, 2Department of Pain Management, Klinikum Dachau, Dachau, 3Pain Clinic, University Medicine, University of Göttingen, 4Day Care Unit, DRK Pain Center, Mainz, 5Interdisciplinary Pain Center, Zentralklinik Bad Berka, Bad Berka, 6Department of Anesthesiology and Intensive Care, University ...

  20. Evaluation of Peripheral Neuropathy of Unknown Origin in an Outpatient Foot and Ankle Practice.

    Science.gov (United States)

    Klein, Sandra E; Chu, Jennifer; McCormick, Jeremy J; Johnson, Jeffrey E

    2015-09-01

    The foot and ankle surgeon can see peripheral neuropathy in the treatment of foot and ankle conditions. The purpose of this study was (1) to evaluate the demographics and presenting complaints of patients diagnosed with idiopathic peripheral neuropathy during an examination by a foot and ankle surgeon and (2) to identify the type and frequency of subsequent diagnosis of medical causes of neuropathy. This was a retrospective study of patients diagnosed with idiopathic peripheral neuropathy in our practice between January 1997 and December 2008. Ninety-five patients were identified, and demographic data, presenting complaints, and medical comorbidities were extracted from the medical record. Examination findings of decreased sensation to Semmes Weinstein 5.07 monofilament testing were documented, and electromyogram and nerve conduction study results were reviewed when available. Laboratory values were noted, as were neurologic evaluations performed to diagnose medical conditions associated with peripheral neuropathy. The most common presentation was foot pain, in 36 patients (38%). Ninety-one patients had Semmes Weinstein 5.07 monofilament testing, with loss of protective sensation reported in 75 of the 91 tested (82%). Only 30 of the 95 patients had electromyogram and nerve conduction study results available, with a test positive for peripheral neuropathy in 20 of the 30 tested. Thirty-two patients were evaluated by a neurologist. A specific cause was identified in 12 of the 32 seen by a neurologist. Of the total group of 95 patients, 31 patients (33%) were diagnosed with a condition that may be associated with peripheral neuropathy. Thirty-three percent of the patients presenting to our clinic and given a diagnosis of idiopathic peripheral neuropathy were ultimately diagnosed with a medical cause of neuropathy-most commonly, diabetes. For those patients with idiopathic neuropathy, a spectrum of disease was encountered, including pain, ulcer, infection, and Charcot