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Sample records for chronic central neuropathic

  1. Chronic motor cortex stimulation in the treatment of central and neuropathic pain. Correlations between clinical, electrophysiological and anatomical data.

    Science.gov (United States)

    Nguyen, J P; Lefaucheur, J P; Decq, P; Uchiyama, T; Carpentier, A; Fontaine, D; Brugières, P; Pollin, B; Fève, A; Rostaing, S; Cesaro, P; Keravel, Y

    1999-09-01

    Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (eight new patients and five reinterventions) were operated by a technique including localisation by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and ten of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zooster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localisation and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

  2. AAPT Diagnostic Criteria for Central Neuropathic Pain

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  3. Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala.

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    Li, Ming-Jia; Liu, Ling-Yu; Chen, Lin; Cai, Jie; Wan, You; Xing, Guo-Gang

    2017-04-01

    Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats. Moreover, we revealed that CFSS induces both sensitization of basolateral amygdala (BLA) neurons and augmentation of long-term potentiation (LTP) at the BLA-CeA synapse and meanwhile, exaggerates both SNI-induced sensitization of CeA neurons and LTP at the parabrachial (PB)-CeA synapse. In addition, we discovered that CFSS elevates SNI-induced functional up-regulation of GluN2B-containing NMDA (GluN2B-NMDA) receptors in the CeA, which is proved to be necessary for CFSS-induced augmentation of LTP at the PB-CeA synapse and exacerbation of pain hypersensitivity in SNI rats. Suppression of CFSS-elicited depressive-like behaviors by antidepressants imipramine or ifenprodil inhibits the CFSS-induced exacerbation of neuropathic pain. Collectively, our findings suggest that CFSS potentiates synaptic efficiency of the BLA-CeA pathway, leading to the activation of GluN2B-NMDA receptors and sensitization of CeA neurons, which subsequently facilitate pain-related synaptic plasticity of the PB-CeA pathway, thereby exacerbating SNI-induced neuropathic pain. We conclude that chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the CeA.

  4. Central Neuropathic Pain in Spinal Cord Injury

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

    2015-01-01

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

  5. [Treatment of central and neuropathic facial pain by chronic stimulation of the motor cortex: value of neuronavigation guidance systems for the localization of the motor cortex].

    Science.gov (United States)

    Nguyen, J P; Lefaucheur, J P; Le Guerinel, C; Fontaine, D; Nakano, N; Sakka, L; Eizenbaum, J F; Pollin, B; Keravel, Y

    2000-11-01

    Thirty two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27. 3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and nine of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the 3 patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localization and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

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

    Directory of Open Access Journals (Sweden)

    Penelope Henwood

    2004-01-01

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

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

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

    2011-05-01

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

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

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

    2014-04-27

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

  9. Pharmacologic management of chronic neuropathic pain

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2018-03-07

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

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

    Science.gov (United States)

    Haanpää, Maija; Paavonen, Jorma

    2004-10-01

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

  12. Motor cortex stimulation in the treatment of central and neuropathic pain.

    Science.gov (United States)

    Nguyen, J P; Lefaucher, J P; Le Guerinel, C; Eizenbaum, J F; Nakano, N; Carpentier, A; Brugières, P; Pollin, B; Rostaing, S; Keravel, Y

    2000-01-01

    Motor cortex stimulation has been proposed for the treatment of central pain. Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated on according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated on by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organization of the motor cortex was established preoperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and 10 of the 12 patients with neuropathic facial pain experienced substantial pain relief (83.3%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. Our results confirm that chronic stimulation of the motor cortex is an effective method in treating certain forms of refractory pain.

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

    Science.gov (United States)

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

    2017-11-06

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2015-10-13

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

  17. Burning Eye Syndrome: Do Neuropathic Pain Mechanisms Underlie Chronic Dry Eye?

    Science.gov (United States)

    Kalangara, Jerry P; Galor, Anat; Levitt, Roy C; Felix, Elizabeth R; Alegret, Ramon; Sarantopoulos, Constantine D

    2016-04-01

    Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This disorder may also involve neuroplasticity in response to neuronal injury. This review will emphasize the key characteristics of dry eye pain and its pathologic mechanisms, making the argument that a subset of dry eye represents a neuropathic pain disorder of the eye, more appropriately called "burning eye syndrome." A literature review was conducted using a PubMed search focusing on dry eye, corneal nociception, and neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic ocular pain as related to dry eye were summarized. We found that there is a discordance between ocular pain and dryness on the ocular surface. Although tear dysfunction may be one of the initial insults, its persistence may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic pain transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome." © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. 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.

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

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

    2014-11-01

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

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

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

    2017-09-01

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

  1. 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.

  2. Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain

    NARCIS (Netherlands)

    Lefaucheur, Jean-Pascal; Holsheimer, J.; Goujon, Colette; Keravel, Yves; Nguyen, Jean-Paul

    Epidural motor cortex stimulation (EMCS) is a therapeutic option for chronic, drug-resistant neuropathic pain, but its mechanisms of action remain poorly understood. In two patients with refractory hand pain successfully treated by EMCS, the presence of implanted epidural cervical electrodes for

  3. Neuropathic Pain Mechanisms in Patients with Chronic Sports Injuries : A Diagnostic Model Useful in Sports Medicine?

    NARCIS (Netherlands)

    van Wilgen, Cornelis P.; Keizer, Doeke

    2011-01-01

    Objective. The pathophysiology of chronic sports injuries such as overuse or tendinopathy remains largely unknown. With this exploratory study, we aim to detect signs of sensitization of the nervous system. Sensitization is an indication of the involvement of neuropathic mechanisms in patients with

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  5. 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...

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

    Science.gov (United States)

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

    2017-10-23

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

  7. The effects of spinal cord stimulation on the neuronal activity of the brain in patients with chronic neuropathic pain

    International Nuclear Information System (INIS)

    Kunitake, Ayumi; Hidaka, Nami; Katsuki, Hiroshi; Iwasaki, Tatsuma; Nagamachi, Shigeki; Takasaki, Mayumi; Uno, Takeshi

    2005-01-01

    The effects of spinal cord stimulation (SCS) on the neuronal activity of the brain were examined by single photon emission computed tomography (SPECT) in patients with chronic neuropathic pain. Regional cerebral blood flow (CBF) in each cortical area and the thalamus decreased in several patients without SCS. Patients with central pain due to thalamic hemorrhage showed a decrease in rCBF in the thalamus contralateral to the painful side. During the stimulation period in SCS, parietal rCBF decreased on the side contralateral to the pain. In contrast, rCBF increased in the bilateral frontal and anterior cingulate cortex and in the contralateral temporal lobe in half of the patients in whom SCS was effective in relieving pain. The decrease in thalamic rCBF in two patients with central pain was improved by the SCS therapy; however, pain was relieved in only one of them. In the majority of patients in whom SCS was not effective, there was no change in rCBF in various cortical areas, even after SCS. These results suggest that, in patients with chronic neuropathic pain, SCS modulates the neuronal activities of several brain areas that are believed to be associated with pain processing. (author)

  8. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    GURPREET KAUR

    2015-03-01

    Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

  9. Neuropathic pain mechanisms in patients with chronic sports injuries: a diagnostic model useful in sports medicine?

    Science.gov (United States)

    van Wilgen, Cornelis P; Keizer, Doeke

    2011-01-01

    The pathophysiology of chronic sports injuries such as overuse or tendinopathy remains largely unknown. With this exploratory study, we aim to detect signs of sensitization of the nervous system. Sensitization is an indication of the involvement of neuropathic mechanisms in patients with chronic sports injuries. Sensory descriptors were assessed by means of a neuropathic pain questionnaire (DN4-interview) and by three methods of sensory testing. The test results were integrated in a scoring system. Patients were recruited from an outpatient clinic of a University Medical Centre and at primary care physical therapy practices. Fifteen athletes with a unilateral chronic sports injury were included. All subjects filled out the seven-items of the DN4-interview to assess sensory descriptors. Next, the presence of brush-evoked allodynia was assessed and pain thresholds with Von Frey monofilaments and a pressure algometer were measured in all patients to determine signs of sensitization. Based on the scoring system, in 4 out of 15 patients (27%) the presence of sensitization could be detected. In two other patients, signs of hypoalgesia were observed. The involvement of sensitization as an explanation for the pain in chronic sports injuries is credible in a considerable proportion of patients. With respect to treatment, the establishment of such neuropathic pain mechanisms is of clinical significance. Wiley Periodicals, Inc.

  10. Central sensitization in chronic low back pain: A narrative review.

    Science.gov (United States)

    Sanzarello, Ilaria; Merlini, Luciano; Rosa, Michele Attilio; Perrone, Mariada; Frugiuele, Jacopo; Borghi, Raffaele; Faldini, Cesare

    2016-11-21

    Low back pain is one of the four most common disorders in all regions, and the greatest contributor to disability worldwide, adding 10.7% of total years lost due to this health state. The etiology of chronic low back pain is, in most of the cases (up to 85%), unknown or nonspecific, while the specific causes (specific spinal pathology and neuropathic/radicular disorders) are uncommon. Central sensitization has been recently recognized as a potential pathophysiological mechanism underlying a group of chronic pain conditions, and may be a contributory factor for a sub-group of patients with chronic low back pain. The purposes of this narrative review are twofold. First, to describe central sensitization and its symptoms and signs in patients with chronic pain disorders in order to allow its recognition in patients with nonspecific low back pain. Second, to provide general treatment principles of chronic low back pain with particular emphasis on pharmacotherapy targeting central sensitization.

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

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    Martinez Jose A

    2012-01-01

    Full Text Available Abstract Background Although pregabalin therapy is beneficial for neuropathic pain (NeP by targeting the CaVα2δ-1 subunit, its site of action is uncertain. Direct targeting of the central nervous system may be beneficial for the avoidance of systemic side effects. Results We used intranasal, intrathecal, and near-nerve chamber forms of delivery of varying concentrations of pregabalin or saline delivered over 14 days in rat models of experimental diabetic peripheral neuropathy and spinal nerve ligation. As well, radiolabelled pregabalin was administered to determine localization with different deliveries. We evaluated tactile allodynia and thermal hyperalgesia at multiple time points, and then analyzed harvested nervous system tissues for molecular and immunohistochemical changes in CaVα2δ-1 protein expression. Both intrathecal and intranasal pregabalin administration at high concentrations relieved NeP behaviors, while near-nerve pregabalin delivery had no effect. NeP was associated with upregulation of CACNA2D1 mRNA and CaVα2δ-1 protein within peripheral nerve, dorsal root ganglia (DRG, and dorsal spinal cord, but not brain. Pregabalin's effect was limited to suppression of CaVα2δ-1 protein (but not CACNA2D1 mRNA expression at the spinal dorsal horn in neuropathic pain states. Dorsal root ligation prevented CaVα2δ-1 protein trafficking anterograde from the dorsal root ganglia to the dorsal horn after neuropathic pain initiation. Conclusions Either intranasal or intrathecal pregabalin relieves neuropathic pain behaviours, perhaps due to pregabalin's effect upon anterograde CaVα2δ-1 protein trafficking from the DRG to the dorsal horn. Intranasal delivery of agents such as pregabalin may be an attractive alternative to systemic therapy for management of neuropathic pain states.

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

    Science.gov (United States)

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

    2017-08-31

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

  13. 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.

  14. Brain activity modifications following spinal cord stimulation for chronic neuropathic pain: A systematic review.

    Science.gov (United States)

    Bentley, L D; Duarte, R V; Furlong, P L; Ashford, R L; Raphael, J H

    2016-04-01

    Spinal cord stimulation (SCS) is believed to exert supraspinal effects; however, these mechanisms are still far from fully elucidated. This systematic review aims to assess existing neurophysiological and functional neuroimaging literature to reveal current knowledge regarding the effects of SCS for chronic neuropathic pain on brain activity, to identify gaps in knowledge, and to suggest directions for future research. Electronic databases and hand-search of reference lists were employed to identify publications investigating brain activity associated with SCS in patients with chronic neuropathic pain, using neurophysiological and functional neuroimaging techniques (fMRI, PET, MEG, EEG). Studies investigating patients with SCS for chronic neuropathic pain and studying brain activity related to SCS were included. Demographic data (age, gender), study factors (imaging modality, patient diagnoses, pain area, duration of SCS at recording, stimulus used) and brain areas activated were extracted from the included studies. Twenty-four studies were included. Thirteen studies used neuroelectrical imaging techniques, eight studies used haemodynamic imaging techniques, two studies employed both neuroelectrical and haemodynamic techniques separately, and one study investigated cerebral neurobiology. The limited available evidence regarding supraspinal mechanisms of SCS does not allow us to develop any conclusive theories. However, the studies included appear to show an inhibitory effect of SCS on somatosensory evoked potentials, as well as identifying the thalamus and anterior cingulate cortex as potential mediators of the pain experience. The lack of substantial evidence in this area highlights the need for large-scale controlled studies of this kind. © 2015 European Pain Federation - EFIC®

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

    Science.gov (United States)

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

    2009-03-01

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

  16. Experiences with spinal cord stimulator in patients with chronic neuropathic back pain.

    Science.gov (United States)

    Gjesdal, Kine; Furnes, Bodil; Dysvik, Elin

    2014-09-01

    Neuropathic pain is a complex, chronic, and disabling condition that has physical, functional, and psychosocial repercussions. Although the estimated prevalence of neuropathic pain in the general population ranges from 1.5% to 8%, neuropathic pain is frequently underdiagnosed and undertreated. The aims of this study were to examine the experience of patients treated with spinal cord stimulation as a pain-relieving treatment and how this may influence the patient's ability to participate in everyday life activities. A qualitative approach based on seven telephone interviews was performed. The participants were recruited from a university hospital in Norway, and all used spinal cord stimulation as a pain-relieving treatment. Qualitative content analysis was used. Two thematic findings emerged: (1) pain relief with spinal cord stimulation as a complex and individual experience and (2) challenges in adaptations in everyday life with spinal cord stimulation. Findings indicate that spinal cord stimulation can offer pain relief that can help patients achieve a meaningful life despite chronic pain. Spinal cord stimulation also may have disadvantages that should be considered before offering this treatment. It seems evident that extended information needs about working mechanism of SCS and precautions as well as follow-up are required to meet unexpected challenges in adaptation. Here the nurse has an important role when informing and following this patient group. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-02-01

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

  18. Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers–Danlos syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Lo TC

    2016-09-01

    Full Text Available Tony Chung Tung Lo,1,* Stephen Tung Yeung,2,* Sujin Lee,1 Kira Skavinski,3 Solomon Liao,4 1Department of Physical Medicine and Rehabilitation, University of California Irvine, Orange, CA, 2Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, 3Department of Palliative Medicine, University of California San Diego, La Jolla, 4Department of Palliative Medicine, University of California Irvine, Orange, CA, USA *These authors contributed equally to this work Objective: Ehlers–Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers–Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. Case report: A 27-year-old Caucasian female with a history of Ehlers–Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions. After a 7-day course of ketamine intravenous infusion under controlled generalized sedation in the intensive care unit, the patient reported a dramatic reduction in pain levels from 7–8 out of 10 to 0–3 out of 10 on a numeric rating scale and had a significant functional improvement. The patient tolerated a reduction in her pain medication regimen, which originally included opioids, gabapentin, pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs. Conclusion: Ketamine infusion treatment has been used in various pain syndromes, including central neuropathic pain, ischemic pain, and regional pain syndrome. Reports have suggested that ketamine modulates pain by the regression of N-methyl-D-aspartate receptor to a resting state. As such, propagation of nociceptive signal to brain is interrupted allowing for the restoration of

  19. Cannabinoids and centrak neuropathic pain. A review (Cannabinoidi e dolore neuropatico centrale. Una rassegna

    Directory of Open Access Journals (Sweden)

    Francesco Crestani

    2014-03-01

    Full Text Available Only recently, the medical community highlighted the pharmacological scientific bases of the effects of Cannabis. The most important active principle, Delta-9-tetrahydrocannabinol was identified in the second half of the last century, and receptors were subsequently identified and endogenous ligands, called endocannabinoids, were characterized. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids have shown analgesic properties, particularly interesting with regard to the central neuropathic pain. This article will review the current knowledge and will give practical guidance on how to proceed in prescribing cannabinoids.

  20. 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...

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

    Science.gov (United States)

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

    2016-03-01

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

  2. 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.

  3. Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

    Science.gov (United States)

    Mert, Tufan; Kurt, Akif Hakan; Altun, İdiris; Celik, Ahmet; Baran, Furkan; Gunay, Ismail

    2017-05-01

    Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Cognitive Impairment in Patients with Chronic Neuropathic or Radicular Pain: An Interaction of Pain and Age

    Directory of Open Access Journals (Sweden)

    Orla Moriarty

    2017-06-01

    Full Text Available A growing body of empirical research has confirmed an association between chronic pain and cognitive dysfunction. The aim of the present study was to determine whether cognitive function is affected in patients with a diagnosis of chronic neuropathic or radicular pain relative to healthy control participants matched by age, gender, and years of education. We also examined the interaction of pain with age in terms of cognitive performance. Some limitations of previous clinical research investigating the effects of chronic pain on cognitive function include differences in the pain and cognitive scale materials used, and the heterogeneity of patient participants, both in terms of their demographics and pathological conditions. To address these potential confounds, we have used a relatively homogenous patient group and included both experimental and statistical controls. We have also specifically investigated the interaction effect of pain and age on cognitive performance. Patients (n = 38 and controls (n = 38 were administered a battery of cognitive tests measuring IQ, spatial and verbal memory, attention, and executive function. Educational level, depressive symptoms, and state anxiety were assessed as were medication usage, caffeine, and nicotine consumption to control for possible confounding effects. Both the level of depressive symptoms and the state anxiety score were higher in chronic pain patients than in matched control participants. Chronic pain patients had a lower estimated IQ than controls, and showed impairments on measures of spatial and verbal memory. Attentional responding was altered in the patient group, possibly indicative of impaired inhibitory control. There were significant interactions between chronic pain condition and age on a number of cognitive outcome variables, such that older patients with chronic pain were more impaired than both age-matched controls and younger patients with chronic pain. Chronic pain did not appear

  5. Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers-Danlos syndrome: a case report.

    Science.gov (United States)

    Lo, Tony Chung Tung; Yeung, Stephen Tung; Lee, Sujin; Skavinski, Kira; Liao, Solomon

    2016-01-01

    Ehlers-Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers-Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. A 27-year-old Caucasian female with a history of Ehlers-Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions. After a 7-day course of ketamine intravenous infusion under controlled generalized sedation in the intensive care unit, the patient reported a dramatic reduction in pain levels from 7-8 out of 10 to 0-3 out of 10 on a numeric rating scale and had a significant functional improvement. The patient tolerated a reduction in her pain medication regimen, which originally included opioids, gabapentin, pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs. Ketamine infusion treatment has been used in various pain syndromes, including central neuropathic pain, ischemic pain, and regional pain syndrome. Reports have suggested that ketamine modulates pain by the regression of N-methyl-D-aspartate receptor to a resting state. As such, propagation of nociceptive signal to brain is interrupted allowing for the restoration of physiological balance between pain inhibition and facilitation. The present report shows that this treatment option can be used in patients with refractory central pain syndrome in the setting of spinal cord myelopathy secondary to Ehlers-Danlos syndrome. In addition, as seen in this case, this protocol can potentially decrease the chronic use of pain medication, such as opioids.

  6. Neuropathic ocular pain due to dry eye is associated with multiple comorbid chronic pain syndromes

    Science.gov (United States)

    Galor, Anat; Covington, Derek; Levitt, Alexandra E.; McManus, Katherine T.; Seiden, Benjamin; Felix, Elizabeth R.; Kalangara, Jerry; Feuer, William; Patin, Dennis J.; Martin, Eden R.; Sarantopoulos, Konstantinos D.; Levitt, Roy C.

    2015-01-01

    Recent data demonstrate that dry eye (DE) susceptibility and other chronic pain syndromes (CPS) such as chronic widespread pain, irritable bowel syndrome and pelvic pain, may share common heritable factors. Previously, we showed that DE patients describing more severe symptoms tended to report features of neuropathic ocular pain (NOP). We hypothesize that patients with a greater number of CPS would have a different DE phenotype compared to those with fewer CPS. We recruited a cohort of 154 DE patients from the Miami Veterans Affairs Hospital and defined high and low CPS groups by cluster analysis. In addition to worse non-ocular pain complaints and higher PTSD and depression scores (Ppain assessed via 3 different pain scales (Ppain disorder, and that shared mechanistic factors may underlie vulnerability to some forms of DE and other comorbid CPS. PMID:26606863

  7. Percutaneous nerve stimulation in chronic neuropathic pain patients due to spinal cord injury: a pilot study.

    Science.gov (United States)

    Kopsky, David Jos; Ettema, Frank Willem Leo; van der Leeden, Marike; Dekker, Joost; Stolwijk-Swüste, Janneke Marjan

    2014-03-01

    The long-term prognosis for neuropathic pain resolution following spinal cord injury (SCI) is often poor. In many SCI patients, neuropathic pain continues or even worsens over time. Thus, new treatment approaches are needed. We conducted a pilot study to evaluate the feasibility and effect of percutaneous (electrical) nerve stimulation (P(E)NS) in SCI patients with chronic neuropathic pain. In 18 weeks, 12 P(E)NS treatments were scheduled. Assessment with questionnaires was performed at baseline (T0), after 8 weeks (T8), 18 weeks (T18), and 12 weeks post-treatment (T30). From 26 screened patients, 17 were included. In total, 91.2% questionnaires were returned, 2 patients dropped out, and 4.2% of the patients reported minor side effects. Pain scores on the week pain diary measured with the numerical rating scale improved significantly at T8, from 6.5 at baseline to 5.4, and were still significantly improved at T18. Pain reduction of ≥ 30% directly after a session was reported in 64.6% sessions. In total, 6 patients experienced reduction in size of the pain areas at T18 and T30, with a mean reduction of 45.8% at T18 and 45.3% at T30. P(E)NS is feasible as an intervention in SCI patients and might have a positive effect on pain reduction in a part of this patient group. © 2013 The Authors Pain Practice © 2013 World Institute of Pain.

  8. Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat

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    Ikeda Hiroshi

    2012-06-01

    Full Text Available Abstract Background The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain. Results In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP. Conclusions These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

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

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    Masato Narita

    2017-01-01

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

  10. A comparison of coping strategies in patients with fibromyalgia, chronic neuropathic pain, and pain-free controls

    DEFF Research Database (Denmark)

    Baastrup, Sidsel; Schultz, Rikke; Brødsgaard, Inger

    2016-01-01

    different groups of chronic pain patients and a group of healthy controls. Thirty neuropathic pain (NP) patients, 28 fibromyalgia (FM) patients, and 26 pain-free healthy controls completed the Coping Strategy Questionnaire (CSQ-48/27) and rated their daily pain. The results showed that FM and NP patients...

  11. Use of high performance technologies in the treatment of chronic neuropathic pain

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    Streltov Ion

    2018-03-01

    Full Text Available Spinal cord neurostimulation is a minimally invasive treatment method for chronic neuropathic pain that is refractory to treatment, and is part of top technology in field. Relatively recent introduction of this method in the Neurosurgery Clinic “Prof. Dr. N. Oblu” of Iasi has aligned the clinic’s therapeutic arsenal to world standards. This has made it possible to treat in Romania a category of patients who would be treated abroad until now. Our clinic has entered the “National Program for diagnostic and treatment using high performance equipment” - Subprogram of treatment of neuropathic pain by implant of a spinal cord neurostimulator and is currently the only one in Romania where this treatment can be done. This represents a new step in the transformation process of the Clinical Hospital Emergency “Prof. Dr. N. Oblu” Iasi in a real Center of Excellence in the field Neurosurgery. The team dealing with the implant consists of 3 neurosurgeons, a neurologist, pa sychologist and an anesthetist, trained in a specialized foreign center.

  12. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

    Science.gov (United States)

    Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

    2009-04-01

    Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

  13. Experienced dilemmas of everyday life in chronic neuropathic pain patients--results from a critical incident study.

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    Hensing, Gunnel K E; Sverker, Annette M; Leijon, Göran S

    2007-06-01

    Neuropathic pain is a disabling chronic condition with limited therapeutic options. Few studies have addressed patient's experience and strategies. The aim of this study was to explore dilemmas experienced in order to improve care and rehabilitation. An interview study with 39 patients suffering from neuropathic pain of different origin was performed. We used the critical incident technique to collect data. Questions on occasions when patients had been hindered by or reminded of their neuropathic pain were included, and the self-perceived consequences and management of such occasions. The interviews were transcribed verbatim and analysed qualitatively. A broad range of experiences categorised into dilemmas, disturbances, consequences and managements from most parts of everyday life was identified. The dilemmas were 'housework', 'sitting', 'physical activity', 'personal hygiene', 'sleeping difficulties', 'hypersensitivity to external stimuli', 'social relationships', 'transportation' and 'leisure time'. Disturbances were 'failures', 'inabilities' and 'restrictions'. Consequences were 'increased pain', 'psychological reactions' and 'physical symptoms'. The majority of the patients used activity-oriented strategies to manage their pain such as alternative ways of performing the task, a cognitive approach or simply ignoring the pain. This is one of the first studies presenting detailed data on everyday dilemmas, disturbances and consequences of patients with chronic neuropathic pain. Such information is important in clinical settings to improve care and rehabilitation.

  14. An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain

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    Onouchi K

    2014-07-01

    patients with chronic central neuropathic pain. Keywords: clinical trial, spinal cord injury, multiple sclerosis, cerebral stroke

  15. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vranken, J. H.; Hollmann, M. W.; van der Vegt, M. H.; Kruis, M. R.; Heesen, M.; Vos, K.; Pijl, A. J.; Dijkgraaf, M. G. W.

    2011-01-01

    The mechanisms underlying central neuropathic pain are poorly understood. Pain inhibitory mechanisms including sertononergic and norepinephrine systems may be dysfunctional. In this randomized, double-blinded, placebo-controlled trial we evaluated the effects of duloxetine on pain relief

  16. Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen

    NARCIS (Netherlands)

    Vranken, J. H.; Dijkgraaf, M. G. W.; Kruis, M. R.; van der Vegt, M. H.; Hollmann, M. W.; Heesen, M.

    2008-01-01

    The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on

  17. Topical gabapentin gel alleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury neuropathic pain model.

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    Shahid, M; Subhan, F; Ahmad, N; Ali, G; Akbar, S; Fawad, K; Sewell, R D E

    2017-04-01

    Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic-mechano-allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat- (PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery. Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes. Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the

  18. Tumor necrosis factor-alpha is a potential diagnostic biomarker for chronic neuropathic pain after spinal cord injury.

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    Xu, Jun; E, Xiaoqiang; Liu, Huiyong; Li, Feng; Cao, Yanhui; Tian, Jun; Yan, Jinglong

    2015-05-19

    Neuropathic pain (NP) is one of the most common complications after spinal cord injury (SCI), but no protein biomarkers has ever been introduced into clinical diagnosis. Previous studies implicated that toll-like receptor (TLR) 4 played a critical role in the development of NP in animal SCI models. Here, a total of 140 participants were recruited, 70 of them were SCI-NP subject and the rest 70 controls did not show neuropathic symptoms. TLR4 was upregulated significantly in SCI-NP patients compared with SCI-noNP subjects. Furthermore, we measured the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), two TLR4 downstream pro-inflammatory cytokines, to assess their diagnostic values. Receiver operating characteristics (ROC) analysis revealed that TNF-α had great potential advantages to predict the progression of neuropathy, the risks of NP were strongly increased in SCI subjects with higher levels of TNF-α (odds ratio: 4.92; 95% confidence interval: 1.89-12.32). These results suggested neuro-immune activation contributed to the development of neuropathic disorder after SCI, and TNF-α could be a potential sensitive diagnostic biomarker for chronic neuropathic pain in SCI patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Living with chronic neuropathic pain after spinal cord injury: an interpretative phenomenological analysis of community experience.

    Science.gov (United States)

    Hearn, Jasmine H; Cotter, Imogen; Fine, Philip; A Finlay, Katherine

    2015-01-01

    This article presents an in-depth, idiographic study examining the lived experience of chronic pain following spinal cord injury (SCI). Neuropathic pain (NP) occurs in a large majority of the SCI population and is particularly intractable to treatment. It can be both psychologically and physically debilitating. This study examines how the experience of NP is mediated by its meaning to the sufferer. Semi-structured interviews were conducted with eight people with SCI and chronic NP, attending outpatient clinics at a specialist SCI Centre in the UK. Verbatim transcripts were subjected to interpretative phenomenological analysis to further understand the experience. Analysis suggested that NP has powerful consequences upon the sufferer's physical, psychological and social well-being, in line with a biopsychosocial understanding of pain. Three super-ordinate themes were identified: a perceived gap between treatments received and participants' views of what they wanted and needed; a fight for life control and acceptance; and feeling understood by others with SCI, but isolated from the non-understanding able-bodied. The results are discussed in terms of the possible application of acceptance-based therapy to NP and the potential for the alleviation of the debilitating consequences of NP. Chronic NP after SCI is often described as worse than the injury itself, often impacting upon the sufferers physical and psychological health. The experiences of persons with SCI-specific NP highlight the impact of pain on their physical, psychological and social health. This indicates that healthcare professionals should incorporate a biopsychosocial approach for managing pain post-SCI. Routine clinical follow-up of SCI patients with chronic NP, as well as comprehensive pain management treatment programmes, could address the three themes evidenced in the current study, by moving routine intervention with NP away from pain relief, towards pain management. Continued education for patients

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  1. Parents' perspective of their journey caring for a child with chronic neuropathic pain.

    Science.gov (United States)

    Gaughan, Veronica; Logan, Deirdre; Sethna, Navil; Mott, Sandra

    2014-03-01

    When a child has chronic pain, it affects the parents. Their response and how it is factored into their lives and family function was the phenomenon of interest that drove this study. The available literature was sparse, especially when the pain etiology was neuropathic. The purpose of this study was to describe the parents' perception of the pain journey from the initial occurrence of their child's pain through the labyrinth of treatment options to successful outcome, to gain a better understanding of parental beliefs about pain, and to learn how parental attitudes and behaviors relate to children's response to treatment for chronic pain. Qualitative descriptive design was used to better understand the phenomenon from those who were the experts because they had experienced it. Parents whose child was enrolled in a pain rehabilitation program participated in open-ended interviews. The children/adolescents were 8-18 years old and diagnosed with complex regional pain syndrome or a related chronic pain condition. During data immersion, the investigators uncovered the pervasive underlying themes of suffering and disempowerment. In addition, the multiple meaning elements were grouped into three categories and supportive subcategories labeled as follows: parent distress, with subcategories schism in parenting, searching, and disabled parenting; and lack of control, with the subcategories family/community, fear, and empowerment. The voices of parents were heard in their description of the exhausting and difficult journey in search of pain relief for their child. Their comments provided insight into how they defined the child's pain and their related parental role. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  2. TRPA1 polymorphisms in chronic and complete spinal cord injury patients with neuropathic pain: a pilot study.

    Science.gov (United States)

    Vidal Rodriguez, Sonia; Castillo Aguilar, Inmaculada; Cuesta Villa, Luis; Serrano Saenz de Tejada, Francisco

    2017-01-01

    Pilot study. Single-nucleotide polymorphisms (SNPs) in TRPA1 gene are related to the etiology of chronic pain. The study is a pilot study with the primary objective of analyzing these SNPs in Spanish patients with chronic and complete spinal cord injury (SCI) and neuropathic pain (NPP). Asepeyo Hospital Department of Chronic and Complete SCI. Twelve patients with chronic and complete SCI and NPP, and 12 patients with chronic and complete SCI with no pain were reviewed. International Spinal Cord Injury Pain Classification (LANSS) and visual analog score (VAS) were chosen to classify pain syndrome. SNPs were identified by melting analysis after DNA amplification with real-time fluorescence PCR. There were differences in rs11988795 variant: GG homozygous ( p  = 0.01) and G allele ( p  = 0.001) were more frequent in SCI patients with no pain. There were differences in rs13255063 variant: TT homozygous were prevalent ( p  = 0.03) in patients with NPP. Until now this is the first study to show a description of TRPA1 SNPs in Spanish patients with chronic and complete SCI and NPP. These results suggest that GG genotype in rs11988795 variant and G allele could be protective factors against NPP. TT genotype in rs13255063 variant could be a risk factor for NPP. Neuropathic pain after spinal cord injuries may have genetic contributions.

  3. Multidimensional study of orofacial chronic neuropathic pain: An experimental study in rats.

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    Claudia Daniela Montes-Angeles

    2017-10-01

    Full Text Available Orofacial neuropathic chronic pain (NCP is frequently attributed to lesions caused by orofacial surgeries and dental treatments. There are many experimental models available to study orofacial NCP, however, many are extremely painful for the animal due to the amplitude of the innervated region. A previously proposed mental nerve constriction model, mNC, was used in this project. Forty Wistar rats were randomly divided into two groups: one group included rats with mNC (n=20, and another rats with sham lesions (n=20. Through the use of the fixed ratio program and the progressive program, a decrease of motivation for a sweet substance, caused by the lesion, was evaluated. The possibility of alterations in cognitive learning and adaptation abilities was also assessed using the go/no-go behavioral task. The mNC group showed low induced and spontaneously evoked pain responses, as well as a decrease in the motivation for sucrose, a sign of anhedonia. This decrease does not depend on taste processing. Finally, although no alterations in the learning-memory process were observed, the mNC group did show alterations when adapting to a new rule.

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

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    Varsha J. Bansode

    2014-01-01

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

  5. Curcumin attenuates the expression of NMDAR-NR1 in Chronic Constructive Injury model of neuropathic pain

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    Xiangdi Yu

    2015-03-01

    Full Text Available Objective: Neuropathic pain is a prevalent desease that greatly impairs the patients’ quality of life. A lack of the understanding of its aetiology, inadequate relief, and development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptic effect of curcumin and its effect on expression of N-methyl-D-aspartate (NMDA receptor in spinal dorsal horn and dorsal root ganglion in chronic constriction injury (CCI mode of neuropathic pain of rats. Methods: Paw withdrawal mechanical threshold (PWMT and paw withdrawal thermal latency (PWTL of rats were measured on 2th pre-operative and 1, 3, 5, 7, 10, 14 post-operative days, and the expression of NMDAR NR-1 in spinal dorsal horn and DRG was measured by Immunohistochemical staining and western-blot. Results: CCI rats exhibited significant hyperalgesia after operation as compared with control rats. Chronic treatment with curcumin 100mg/kg/day for 14days starting from the 1 th day after CCI operation significantly attenuated PWMT and PWTL. Curcumin also inhibited the expression of NMDAR NR-1 in spinal dorsal horn and DRG. Conclusion: These results indicate an antinociceptive activity of curcumin possibly through its inhibitory action on expression of NMDAR NR-1 in spinal dorsal horn and DRG and point towards its potential to attenuate neuropathic pain.

  6. [Expressions of neuropathic pain-related proteins in the spinal cord dorsal horn in rats with bilateral chronic constriction injury].

    Science.gov (United States)

    Shen, Le; Li, Xu; Wang, Hai-tang; Yu, Xue-rong; Huang, Yu-guang

    2013-12-01

    To evaluate the pain-related behavioral changes in rats with bilateral chronic constriction injury(bCCI)and identify the expressions of neuropathic pain-related proteins. The bCCI models were established by ligating the sciatic nerves in female Sprague Dawley rats. Both mechanical hyperalgesia and cold hyperalgesia were evaluated through electronic von Frey and acetone method. Liquid chromatography-mass spectrometry/mass spectrometry was applied to characterize the differentially expressed proteins. Both mechanical withdrawal threshold and cold hyperalgesia threshold decreased significantly on the postoperative day 7 and 14, when compared with na ve or sham rats(P <0.05). Twenty five differentially expressed proteins associated with bilateral CCI were discovered, with eighteen of them were upregulated and seven of them downregulated. The bCCT rats have remarkably decreased mechanical and cold hyperalgesia thresholds. Twenty five neuropathic pain-related proteins are found in the spinal cord dorsal horn.

  7. Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord.

    Science.gov (United States)

    Sufianov, A A; Shapkin, A G; Sufianova, G Z; Elishev, V G; Barashin, D A; Berdichevskii, V B; Churkin, S V

    2014-08-01

    Changes in functional and metabolic activities of the brain were evaluated by EEG and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients with neuropathic pain syndrome previous to and 3 months after implantation of a system for chronic epidural spinal cord stimulation. In most cases, the use of a nerve stimulator was followed by alleviation of neuropathic pain and partial normalization of functional and metabolic activities of brain structures responsible for pain perception, emotiogenic, behavioral, and autonomic responses.

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

    Science.gov (United States)

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

    2015-12-01

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

  9. The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats

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    Di Marzo Vincenzo

    2011-01-01

    Full Text Available Abstract Background Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1 and the catabolic enzyme fatty acid amide hydrolase (FAAH in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL cortex in neuropathic rats. Results The effect of N-arachidonoyl-serotonin (AA-5-HT, a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. Conclusion These data suggest a possible involvement of endovanilloids in the cortical

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

    Science.gov (United States)

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

    2014-06-01

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

  11. Pharmacological Management of Chronic Neuropathic Pain – Consensus Statement and Guidelines from the Canadian Pain Society

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    DE Moulin

    2007-01-01

    Full Text Available Neuropathic pain (NeP, generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics and anticonvulsants (gabapentin and pregabalin. Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.

  12. [Effectiveness and safety of oxcarbazepine in chronic neuropathic pain: a study of 40 cases].

    Science.gov (United States)

    Fenollosa-Vázquez, P; Canós-Verdecho, M A; Núñez-Cornejo, C; Pallarés-Delgado, J

    Neuropathic pain (NP) often fails to respond to the commonly established analgesic treatment. This fact, together with the existence of side effects, has led to the need to evaluate the analgesic effectiveness of antiepileptic drugs, which, as in the case of oxcarbazepine (OXC), are a valid alternative. The aim of this study was to evaluate the effectiveness and safety of OXC in patients suffering from chronic NP. We conducted a prospective, open study involving a series of 40 patients diagnosed with a long history of NP, which was previously resistant to different kinds of treatment with anticonvulsants, non-steroidal anti-inflammatory (NSAI) drugs, opiates and adjuncts. Patients were treated with OXC and they were evaluated in both the basal (prior to treatment) and final visits (after treatment) by means of the visual analogue scale (VAS), SF-McGill questionnaire and the Lattinen test. The patient's general impression of the result was also obtained. The statistical analysis was performed by calculating the "effect size", by computing Cohen's d. Treatment with OXC diminishes different symptomatic variations of this pain, but especially so in the case of lancinating discharges (d = 0.87, important effect) and burning pain (d = 0.60, moderate-important effect), although the allodynia (d = 0.48, moderate effect) also improved with treatment. In the opinion of the patients themselves, response to treatment was good or very good in 50% of cases. The chief side effects observed were dizziness, drowsiness and abdominal upsets. OXC can be seen as a therapeutic alternative to be taken very much into account in patients with NP having different aetiologies; it has a good benefit-risk ratio and is a form of treatment that is well accepted by patients.

  13. 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.

  14. 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...

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

    Directory of Open Access Journals (Sweden)

    Selvaraj Deepitha

    2010-03-01

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

  16. The Role of Ventral Tegmental Area Gamma-Aminobutyric Acid in Chronic Neuropathic Pain after Spinal Cord Injury in Rats.

    Science.gov (United States)

    Ko, Moon Yi; Jang, Eun Young; Lee, June Yeon; Kim, Soo Phil; Whang, Sung Hun; Lee, Bong Hyo; Kim, Hee Young; Yang, Chae Ha; Cho, Hee Jung; Gwak, Young S

    2018-04-20

    Spinal cord injury (SCI) frequently results in chronic neuropathic pain (CNP). However, the understanding of brain neural circuits in CNP modulation is unclear. The present study examined the changes of ventral tegmental area (VTA) putative GABAergic and dopaminergic neuronal activity with CNP attenuation in rats. SCI was established by T10 clip compression injury (35 g, 1 min) in rats, and neuropathic pain behaviors, in vivo extracellular single-cell recording of putative VTA gamma-aminobutyric acid (GABA)/dopamine neurons, extracellular GABA level, glutamic acid decarboxylase (GAD), and vesicular GABA transporters (VGATs) were measured in the VTA, respectively. The results revealed that extracellular GABA level was significantly increased in the CNP group (50.5 ± 18.9 nM) compared to the sham control group (10.2 ± 1.7 nM). In addition, expression of GAD 65/67 , c-Fos, and VGAT exhibited significant increases in the SCI groups compared to the sham control group. With regard to neuropathic pain behaviors, spontaneous pain measured by ultrasound vocalizations (USVs) and evoked pain measured by paw withdrawal thresholds showed significant alteration, which was reversed by intravenous (i.v.) administration of morphine (0.5-5.0 mg/kg). With regard to in vivo electrophysiology, VTA putative GABAergic neuronal activity (13.6 ± 1.7 spikes/sec) and putative dopaminergic neuronal activity (2.4 ± 0.8 spikes/sec) were increased and decreased, respectively, in the SCI group compared to the sham control group. These neuronal activities were reversed by i.v. administration of morphine. The present study suggests that chronic increase of GABAergic neuronal activity suppresses dopaminergic neuronal activity in the VTA and is responsible for negative emotion and motivation for attenuation of SCI-induced CNP.

  17. 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.

  18. 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.

  19. A pilot study of healing touch and progressive relaxation for chronic neuropathic pain in persons with spinal cord injury.

    Science.gov (United States)

    Wardell, Diane Wind; Rintala, Diana H; Duan, Zhigang; Tan, Gabriel

    2006-12-01

    This pilot study assessed the role of Healing Touch (HT), an energy-based therapy, in modulating chronic neuropathic pain and the associated psychological distress from post spinal cord injury. Twelve veterans were assigned to either HT or guided progressive relaxation for six weekly home visits. The instruments selected showed sensitivity, although there was a large variation among the groups. There was a significant difference in the composite of interference on the Brief Pain Inventory (t = -2.71, p = .035). The mean score of the fatigue subscale of the Profile of Moods decreased (ns) in the HT group and in the subscale of confusion yet remained stable in the control group. The Diener Satisfaction With Life Scale showed increased well-being in the HT group and no change in the control group. Participants reported various experiences with HT sessions indicating that it may have benefit in the complex response to chronic pain.

  20. Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain

    NARCIS (Netherlands)

    Vries, M. de; Wilder-Smith, O.H.G.; Jongsma, M.L.A.; Broeke, E.N. van den; Arns, M.W.; Goor, H. van; Rijn, C.M. van

    2013-01-01

    OBJECTIVES: Electroencephalography (EEG) may be a promising source of physiological biomarkers accompanying chronic pain. Several studies in patients with chronic neuropathic pain have reported alterations in central pain processing, manifested as slowed EEG rhythmicity and increased EEG power in

  1. Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain

    NARCIS (Netherlands)

    Vries, M. de; Wilder-Smith, O.H.G.; Jongsma, M.L.A.; Broeke, E.N. van den; Arns, M.W.; Goor, H. van; Rijn, C.M. van

    2013-01-01

    Objectives: Electroencephalography (EEG) may be a promising source of physiological biomarkers accompanying chronic pain. Several studies in patients with chronic neuropathic pain have reported alterations in central pain processing, manifested as slowed EEG rhythmicity and increased EEG power in

  2. The Evaluation of the Effect of Neuropathic Pain on Functional Disability in Patients with Chronic Low Back Pain

    Directory of Open Access Journals (Sweden)

    Yalkın Çalık

    2015-12-01

    Full Text Available Objective: The aim of this study was to evaluate both the prevalence of neuropathic pain (NP and the effect of functional disability of NP in patients with chronic low back pain (CLBP. Materials and Methods: In this study, outpatients data were reviewed retrospectively from January 2014 to December 2014 to determine the patients with CLBP. 190 patients with CLBP meeting the inclusion criteria were included. NP scores of the patients were assessed using Leeds Assessment of Neuropathic Symptoms and Signs (LANSS and the evaluation of pain was performed using the Visual analoque scale (VAS and functional disability scores was determined by the Oswestry disability index (ODI. Results: In this study NP was detected in 39.4% of the patients with CLBP. The number of female patients with NP (n=60, %80 was significantly higher than the number of male patients with NP (n=15, %20, (p<0.05. ODI and VAS scores of the patients with NP [(19.81±7.28, (5.08±0.76] was significantly higher than those of the patients without NP [(15.28±6.83, (4.44±1.14], (p<0,001. Conclusion: It was found that the co-existence of NP with CLBP increases pain and functional disability.

  3. The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury.

    Science.gov (United States)

    Corona-Ramos, Janette Nallely; De la O-Arciniega, Minarda; Déciga-Campos, Myrna; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

    2016-08-01

    Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016.   © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

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    VENKATA R.K. THIAGARAJAN

    2014-09-01

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

  5. The Development of Translational Biomarkers as a Tool for Improving the Understanding, Diagnosis and Treatment of Chronic Neuropathic Pain.

    Science.gov (United States)

    Buckley, David A; Jennings, Elaine M; Burke, Nikita N; Roche, Michelle; McInerney, Veronica; Wren, Jonathan D; Finn, David P; McHugh, Patrick C

    2018-03-01

    Chronic neuropathic pain (CNP) is one of the most significant unmet clinical needs in modern medicine. Alongside the lack of effective treatments, there is a great deficit in the availability of objective diagnostic methods to reliably facilitate an accurate diagnosis. We therefore aimed to determine the feasibility of a simple diagnostic test by analysing differentially expressed genes in the blood of patients diagnosed with CNP of the lower back and compared to healthy human controls. Refinement of microarray expression data was performed using correlation analysis with 3900 human 2-colour microarray experiments. Selected genes were analysed in the dorsal horn of Sprague-Dawley rats after L5 spinal nerve ligation (SNL), using qRT-PCR and ddPCR, to determine possible associations with pathophysiological mechanisms underpinning CNP and whether they represent translational biomarkers of CNP. We found that of the 15 potential biomarkers identified, tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene expression was upregulated in chronic neuropathic lower back pain (CNBP) (p = 0.0049) which positively correlated (R = 0.68, p = ≤0.05) with increased plasma TIMP1 levels in this group (p = 0.0433). Moreover, plasma TIMP1 was also significantly upregulated in CNBP than chronic inflammatory lower back pain (p = 0.0272). In the SNL model, upregulation of the Timp1 gene was also observed (p = 0.0058) alongside a strong trend for the upregulation of melanocortin 1 receptor (p = 0.0847). Our data therefore highlights several genes that warrant further investigation, and of these, TIMP1 shows the greatest potential as an accessible and translational CNP biomarker.

  6. Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

    Science.gov (United States)

    Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

    2016-03-01

    Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest

  7. Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain : Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review

    NARCIS (Netherlands)

    Kurt, Erkan; Henssen, Dylan J. H. A.; Steegers, Monique; Staal, Michiel; Beese, Ulrich; Maarrawi, Joseph; Pirotte, Benoit; Garcia-Larrea, Luis; Rasche, Dirk; Vesper, Jan; Holsheimer, Jan; Duyvendak, Wim; Herregodts, Patrick; van Dongen, Robert; Moens, Maarten

    2017-01-01

    BACKGROUND: Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-05

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  10. Experimental Gene Therapy with Serine-Histogranin and Endomorphin 1 for the Treatment of Chronic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Stanislava Jergova

    2017-12-01

    Full Text Available The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain is a serious medical problem. The enhanced glutamate signaling via NMDA receptors appears to be one of the key events in the development of chronic pain. Although effective, clinical use of systemic NMDA antagonists is limited by adverse effects such as hallucinations and motor dysfunction. Opioids are also potent analgesics but their chronic use is accompanied by tolerance and risk of addiction. However, combination of NMDA antagonists and opioids seems to provide a stable pain relieve at subthreshold doses of both substances, eliminating development of side effects. Our previous research showed that combined delivery of NMDA antagonist Serine histrogranin (SHG and endomorphin1 (EM1 leads to attenuation of acute and chronic pain. The aim of this study was to design and evaluate an analgesic potency of the gene construct encoding SHG and EM1. Constructs with 1SHG copy in combination with EM1, 1SHG/EM1, and 6SHG/EM1 were intraspinally injected to animals with peripheral nerve injury-induced pain (chronic constriction injury, CCI or spinal cord injury induced pain (clip compression model, SCI and tactile and cold allodynia were evaluated. AAV2/8 particles were used for gene delivery. The results demonstrated 6SHG/EM1 as the most efficient for alleviation of pain-related behavior. The effect was observed up to 8 weeks in SCI animals, suggesting the lack of tolerance of possible synergistic effect between SHG and EM1. Intrathecal injection of SHG antibody or naloxone attenuated the analgesic effect in treated animals. Biochemical and histochemical evaluation confirmed the presence of both peptides in the spinal tissue. The results of this study showed that the injection of AAV vectors encoding combined SHG/EM constructs can provide long term attenuation of pain without overt adverse side effects. This approach may provide better treatment options for

  11. Synergistic interaction between total glucosides and total flavonoids on chronic constriction injury induced neuropathic pain in rats.

    Science.gov (United States)

    Zhang, Juan; Lv, Chen; Wang, Hai-na; Cao, Yi

    2013-04-01

    Shaoyao Gancao Decoction (SGD), a famous herbal medicine, consists of two herbs (Paeoniae Radix and Glycyrrhizae Radix) and is traditionally used for the treatment of pain. To investigate the synergistic potential of total glucosides of Paeoniae Radix (TGP) and total flavonoids of Glycyrrhizae Radix (TFL). Oral administration of TGP and TFL alone at the doses of 60,120 and 240 mg/kg or in combination were given only one time to the neuropathic pain rat induced by chronic constriction injury. Paw pressure and heat immersion tests were performed to assess degrees of mechanical allodynia and thermal hyperalgesia, respectively. Synergistic interactions between TGP and TFL were characterized using isobolographic analysis. Expressions of Sirt1 protein were detected by immunohistochemistry. On day 14 after surgery, single oral administration of TGP and TFL both produced significant anti-allodynic and anti-hyperalgesic effects in dose-dependent and time-dependent manners. The ED(50) value of TGP was 249.4 ± 10.8 mg/kg while TFL was 871.4 ± 30.5 mg/kg. Isobolographic analysis revealed that the combination of TGP with TFL at the fixed ratios of 3:1 exerted the highest sub-additive (synergistic) interaction, of which the experimental ED(50) value was 95.1 ± 9.0 mg/kg. SGD could also downregulate Sirt1 protein expression, which was 4.2-fold higher than that of model rats in dorsal root ganglion. Analgesic effects of SGD may contribute to simultaneous inhibition of Sirt1 overexpression and could warrant further evaluation as a possible agent for the treatment of neuropathic pain.

  12. Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages

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    Norikazu Kiguchi

    2017-11-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

  14. Adherence of French GPs to chronic neuropathic pain clinical guidelines: results of a cross-sectional, randomized, "e" case-vignette survey.

    Directory of Open Access Journals (Sweden)

    Valéria Martinez

    Full Text Available BACKGROUND AND AIMS: The French Pain Society published guidelines for neuropathic pain management in 2010. Our aim was to evaluate the compliance of GPs with these guidelines three years later. METHODS: We used "e" case vignette methodology for this non interventional study. A national panel of randomly selected GPs was included. We used eight "e" case-vignettes relating to chronic pain, differing in terms of the type of pain (neuropathic/non neuropathic, etiology (cancer, postoperative pain, low back pain with or without radicular pain, diabetes and symptoms. GPs received two randomly selected consecutive "e" case vignettes (with/without neuropathic pain. We analyzed their ability to recognize neuropathic pain and to prescribe appropriate first-line treatment. RESULTS: From the 1265 GPs in the database, we recruited 443 (35.0%, 334 of whom logged onto the web site (26.4% and 319 (25.2% of whom completed the survey. Among these GPs, 170 (53.3% were aware of the guidelines, 136 (42.6% were able to follow them, and 110 (34.5% used the DN4 diagnostic tool. Sensitivity for neuropathic pain recognition was 87.8% (CI: 84.2%; 91.4%. However, postoperative neuropathic pain was less well diagnosed (77.9%; CI: 69.6%; 86.2% than diabetic pain (95.2%; CI: 90.0%; 100.0%, cancer pain (90.6%; CI: 83.5%; 97.8% and typical radicular pain (90.7%; CI: 84.9%; 96.5%. When neuropathic pain was correctly recognized, the likelihood of appropriate first-line treatment prescription was 90.6% (CI: 87.4%; 93.8%. The treatments proposed were pregabaline (71.8%, gabapentine (43.9%, amiptriptylline (23.2% and duloxetine (18.2%. However, ibuprofen (11%, acetaminophen-codeine (29.5% and clonazepam (10% were still prescribed. CONCLUSIONS: The compliance of GPs with clinical practice guidelines appeared to be satisfactory, but differed between etiologies.

  15. Assessment and manifestation of central sensitisation across different chronic pain conditions.

    Science.gov (United States)

    Arendt-Nielsen, L; Morlion, B; Perrot, S; Dahan, A; Dickenson, A; Kress, H G; Wells, C; Bouhassira, D; Mohr Drewes, A

    2018-02-01

    Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation. Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based

  16. Finasteride for chronic central serous chorioretinopathy.

    Science.gov (United States)

    Forooghian, Farzin; Meleth, Annal D; Cukras, Catherine; Chew, Emily Y; Wong, Wai T; Meyerle, Catherine B

    2011-04-01

    To evaluate the safety and efficacy of finasteride, an inhibitor of dihydrotestosterone synthesis, in the treatment of chronic central serous chorioretinopathy. Five patients with chronic central serous chorioretinopathy were prospectively enrolled in this pilot study. Patients were administered finasteride (5 mg) daily for 3 months, after which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity, central subfield macular thickness, and subretinal fluid volume as assessed by optical coherence tomography. Serum dihydrotestosterone, serum testosterone, and urinary cortisol were also measured. There was no change in mean best-corrected visual acuity. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months and rose to levels that were below baseline by 6 months. The changes in both optical coherence tomography parameters paralleled those in serum dihydrotestosterone level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased after discontinuation of finasteride. In the remaining patient, both optical coherence tomography parameters normalized with finasteride and remained stable when the study medication was discontinued. Finasteride may represent a novel medical treatment for chronic central serous chorioretinopathy. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of central serous chorioretinopathy.

  17. Central blood pressure and chronic kidney disease

    Science.gov (United States)

    Ohno, Yoichi; Kanno, Yoshihiko; Takenaka, Tsuneo

    2016-01-01

    In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD. PMID:26788468

  18. Increased psychological distress among individuals with spinal cord injury is associated with central neuropathic pain rather than the injury characteristics.

    Science.gov (United States)

    Gruener, Hila; Zeilig, Gabi; Laufer, Yocheved; Blumen, Nava; Defrin, Ruth

    2018-02-01

    Cross-sectional study. Central neuropathic pain (CNP) is common after spinal cord injury (SCI). The psychological impact of CNP is not clear. Previous studies reported depression and pain catastrophizing among patients with SCI and CNP; however, the lack of control groups prevented discerning whether these were attributed to CNP or to the SCI itself. The aim was to examine the psychological distress among individuals with SCI with and without CNP and controls to evaluate its impact and possible source. Outpatient clinic of a large rehabilitation center. Individuals with SCI and CNP (n = 27) and without CNP (n = 23), and able-bodied controls (n = 20) participated. Data collection included sociodemographics, SCI characteristics, and level of post-traumatic stress disorder (PTSD), anxiety, stress, depression, and pain catastrophizing. The sensory, affective, and cognitive dimensions of CNP were analyzed. Individuals with SCI and CNP exhibited elevated levels of PTSD, anxiety, stress, depression, and pain catastrophizing compared to the two control groups, which presented similar levels. The psychological variables among the CNP group correlated positively only with the affective dimension of CNP. Neither CNP nor the psychological variables correlated with SCI characteristics. Irrespective of CNP intensity, the affective dimension (suffering) is associated with increased psychological distress. Perhaps individual differences in the response to SCI and/or individual traits rather than the mere exposure to SCI may have a role in the emergence of CNP and psychological distress/mood dysfunction. Rehabilitation programs should prioritize stress management and prevention among individuals with SCI and CNP.

  19. The evidence for pharmacological treatment of neuropathic pain.

    Science.gov (United States)

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

    2010-09-01

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

  20. 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...

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

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    Feng Liang

    2017-05-01

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

  2. 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.

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

    Science.gov (United States)

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

    2016-04-21

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

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Neuropathic pain: targeting the melatonin MT receptor

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2014-09-01

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

  8. Ameliorative potential of Butea monosperma on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    Venkata R.K. Thiagarajan

    2012-12-01

    Full Text Available The present study was designed to investigate the ameliorative role of ethanolic extract from leaves of Butea monosperma in chronic constriction injury (CCI of sciatic nerve induced neuropathic pain in rats. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia & allodynia in the left hind paw and tail thermal hyperalgesia. Further on, thiobarbituric acid reactive substances (TBARS, reduced glutathione (GSH and total calcium levels were estimated to assess the biochemical changes in the sciatic nerve tissue. Histopathological changes were also observed in the sciatic nerve tissue. Ethanolic extract of Butea monosperma leaves and pregabalin (serving as positive control were administered for 14 consecutive days starting from the day of surgery. CCI resulted in significant changes in behavioural and biochemical parameters. Pretreatment of Butea monosperma attenuated CCI induced development of behavioural, biochemical and histopathological alterations in a dose dependent manner, which is comparable to that of pregabalin pretreated group. These findings may be attributed to its potential anti-oxidative, neuroprotective and calcium channel modulatory actions of Butea monosperma.O presente trabalho visou investigar o papel do extrato etanólico de folhas de Butea monosperma no alívio da dor neuropática pela injúria de constrição crônica (CCI do nervo ciático induzida em ratos. Placa quente, gota de acetona, pressão na pata, testes de imersão de pelo e cauda de Von Frey foram utilizados para acessar o grau de hiperalgesia térmica, alodinia química fria, hiperalgesia mecânica e alodinia na pata trazeira esquerda e hiperalgesia térmica da cauda. Além disso, substâncias reativas com ácido tiobarbitúrico (TBARS, glutatião reduzido (GSH e níveis de cálcio total foram estimados para acessar as altera

  9. Neural Mobilization Treatment Decreases Glial Cells and Brain-Derived Neurotrophic Factor Expression in the Central Nervous System in Rats with Neuropathic Pain Induced by CCI in Rats

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    Aline Carolina Giardini

    2017-01-01

    Full Text Available Background. Glial cells are implicated in the development of chronic pain and brain-derived neurotropic factor (BDNF released from activated microglia contributes to the nociceptive transmission. Neural mobilization (NM technique is a method clinically effective in reducing pain sensitivity. Here we examined the involvement of glial cells and BDNF expression in the thalamus and midbrain after NM treatment in rats with chronic constriction injury (CCI. CCI was induced and rats were subsequently submitted to 10 sessions of NM, every other day, beginning 14 days after CCI. Thalamus and midbrain were analyzed for glial fibrillary acidic protein (GFAP, microglial cell OX-42, and BDNF using Immunohistochemistry and Western blot assays. Results. Thalamus and midbrain of CCI group showed increases in GFAP, OX-42, and BDNF expression compared with control group and, in contrast, showed decreases in GFAP, OX-42, and BDNF after NM when compared with CCI group. The decreased immunoreactivity for GFAP, OX-42, and BDNF in ventral posterolateral nucleus in thalamus and the periaqueductal gray in midbrain was shown by immunohistochemistry. Conclusions. These findings may improve the knowledge about the involvement of astrocytes, microglia, and BDNF in the chronic pain and show that NM treatment, which alleviates neuropathic pain, affects glial cells and BDNF expression.

  10. 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.

  11. 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.

  12. Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults.

    Science.gov (United States)

    Wiffen, Philip J; Knaggs, Roger; Derry, Sheena; Cole, Peter; Phillips, Tudor; Moore, R Andrew

    2016-12-27

    Paracetamol, either alone or in combination with codeine or dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double-blind studies. To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries. We included randomised, double-blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or dihydrocodeine, with placebo or another active treatment in chronic neuropathic pain. Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE. No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect. There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.

  13. Optical inactivation of the anterior cingulate cortex modulate descending pain pathway in a rat model of trigeminal neuropathic pain created via chronic constriction injury of the infraorbital nerve

    Directory of Open Access Journals (Sweden)

    Moon HC

    2017-10-01

    Full Text Available Hyeong Cheol Moon,1 Won Ik Heo,2 Yon Ji Kim,3 Daae Lee,4 So Yoon Won,5 Hong Rae Kim,1 Seung Man Ha,1 Youn Joo Lee,6 Young Seok Park1 1Department of Medical Neuroscience and Neurosurgery, College of Medicine, 2Department of Veterinary, College of Veterinary Medicine, 3Department of Biology, College of Natural Sciences, 4Department of Advanced Material Engineering, College of Engineering, 5Biochemistry and Medical Research Center, Chungbuk National University, Cheongju, 6Department of Radiology, Daejoen St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea Purpose: The anterior cingulate cortex (ACC plays a critical role in the initiation, development, and maintenance of neuropathic pain. Recently, the effects of optical stimulation on pain have been investigated, but the therapeutic effects of optical stimulation on trigeminal neuralgia (TN have not been clearly shown. Here, we investigated the effects of optical inhibition of the ACC on TN lesions to determine whether the alleviation of pain affects behavior performance and thalamic neuron signaling.Materials and methods: TN lesions were established in animals by generating a chronic constriction injury of the infraorbital nerve, and the animals received injections of AAV-hSyn-eNpHR3.0-EYFP or a vehicle (phosphate-buffered saline [PBS] in the ACC. The optical fiber was fixed into the ipsilateral ACC after the injection of adeno-associated virus plasmids or vehicle. Behavioral testing, consisting of responses to an air puff and cold allodynia, was performed, and thalamic neuronal activity was monitored following optical stimulation in vivo. Optical stimulation experiments were executed in three steps: during pre-light-off, stimulation-light-on, and post-light-off states. The role of the optical modulation of the ACC in response to pain was shown using a combination of optical stimulation and electrophysiological recordings in vivo.Results: Mechanical thresholds and

  14. 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.

  15. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia.

    Science.gov (United States)

    Pfau, Doreen B; Krumova, Elena K; Treede, Rolf-Detlef; Baron, Ralf; Toelle, Thomas; Birklein, Frank; Eich, Wolfgang; Geber, Christian; Gerhardt, Andreas; Weiss, Thomas; Magerl, Walter; Maier, Christoph

    2014-05-01

    Age- and gender-matched reference values are essential for the clinical use of quantitative sensory testing (QST). To extend the standard test sites for QST-according to the German Research Network on Neuropathic Pain-to the trunk, we collected QST profiles on the back in 162 healthy subjects. Sensory profiles for standard test sites were within normal interlaboratory differences. QST revealed lower sensitivity on the upper back than the hand, and higher sensitivity on the lower back than the foot, but no systematic differences between these trunk sites. Age effects were significant for most parameters. Females exhibited lower pressure pain thresholds (PPT) than males, which was the only significant gender difference. Values outside the 95% confidence interval of healthy subjects (considered abnormal) required temperature changes of >3.3-8.2 °C for thermal detection. For cold pain thresholds, confidence intervals extended mostly beyond safety cutoffs, hence only relative reference data (left-right differences, hand-trunk differences) were sufficiently sensitive. For mechanical detection and pain thresholds, left-right differences were 1.5-2.3 times more sensitive than absolute reference data. The most sensitive parameter was PPT, where already side-to-side differences >35% were abnormal. Compared to trunk reference data, patients with postherpetic neuralgia exhibited thermal and tactile deficits and dynamic mechanical allodynia, mostly without reduced mechanical pain thresholds. This pattern deviates from other types of neuropathic pain. QST reference data for the trunk will also be useful for patients with postthoracotomy pain or chronic back pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  16. Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.

    Science.gov (United States)

    Fandel, Thomas M; Trivedi, Alpa; Nicholas, Cory R; Zhang, Haoqian; Chen, Jiadong; Martinez, Aida F; Noble-Haeusslein, Linda J; Kriegstein, Arnold R

    2016-10-06

    Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Neuropathic low back pain in clinical practice.

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

    Wang, Dongmei; Couture, Réjean; Hong, Yanguo

    2014-04-05

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

  19. Concentration-Effect Relationship of Intrapritoneal Administration of 1, 25 (OH 2-Vitamin D in a Chronic Constriction Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Farinaz Nasirinezhad

    2011-04-01

    Full Text Available Introduction:  Results: These findings revealed the exaggerated responses in the group which received CCI. The group which was treated by 1 μg/kg of 1,25 vit D3 showed a significant reduction in pain behavior. Injection of 1,25 vit D3 did not change the response of animals to the acetone drop and von frey filament. Discussion: Our results showed that antinoceptive effect of 1,25 vit D3 in a rodent neuropathic pain model is dose dependent and this vitamin may provide new approach for treatment of chronic pain.The presence of nuclear receptors of 1,25 dihydroxy vitamin D3 (1,25 vit D3, the biologically active metabolite of vitamin D, in neurons and glial cells indicates the biological effect of this vitamin in the nervous system. The present experiment was conducted to identify the effects of different doses of 1,25 vit D3 on mechanical and cold allodynia in rodent model of neuropatinc pain. Methods: A mononeuropathy was produced by chronic constrictive injury (CCI of the sciatic nerve. 1,25 vit D3 (0.3, 0.6 ,1 μg/Kg was administered by an i.p. injection every 2 days during a month after CCI. Mechanical and cold allodynia were evaluated by Von frey filament and acetone respectively.

  20. Altered central pain processing after pancreatic surgery for chronic pancreatitis

    NARCIS (Netherlands)

    Bouwense, S. A.; Ahmed Ali, U.; ten Broek, R. P.; Issa, Y.; van Eijck, C. H.; Wilder-Smith, O. H.; van Goor, H.

    2013-01-01

    Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP. Patients with CP

  1. Spinal cord stimulation for neuropathic pain: current perspectives

    OpenAIRE

    Wolter, Tilman

    2014-01-01

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

  2. EFNS guidelines on neurostimulation therapy for neuropathic pain

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  3. Analgesic Microneedle Patch for Neuropathic Pain Therapy.

    Science.gov (United States)

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

    2017-01-24

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

  4. 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

  5. Neuropathic ocular pain: an important yet underevaluated feature of dry eye

    Science.gov (United States)

    Galor, A; Levitt, R C; Felix, E R; Martin, E R; Sarantopoulos, C D

    2015-01-01

    Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain. PMID:25376119

  6. Impact of locomotion training with a neurologic controlled hybrid assistive limb (HAL) exoskeleton on neuropathic pain and health related quality of life (HRQoL) in chronic SCI: a case study (.).

    Science.gov (United States)

    Cruciger, Oliver; Schildhauer, Thomas A; Meindl, Renate C; Tegenthoff, Martin; Schwenkreis, Peter; Citak, Mustafa; Aach, Mirko

    2016-08-01

    Chronic neuropathic pain (CNP) is a common condition associated with spinal cord injury (SCI) and has been reported to be severe, disabling and often treatment-resistant and therefore remains a clinical challenge for the attending physicians. The treatment usually includes pharmacological and/or nonpharmacological approaches. Body weight supported treadmill training (BWSTT) and locomotion training with driven gait orthosis (DGO) have evolved over the last decades and are now considered to be an established part in the rehabilitation of SCI patients. Conventional locomotion training goes along with improvements of the patients' walking abilities in particular speed and gait pattern. The neurologic controlled hybrid assistive limb (HAL®, Cyberdyne Inc., Ibraki, Japan) exoskeleton, however, is a new tailored approach to support motor functions synchronously to the patient's voluntary drive. This report presents two cases of severe chronic and therapy resistant neuropathic pain due to chronic SCI and demonstrates the beneficial effects of neurologic controlled exoskeletal intervention on pain severity and health-related quality of life (HRQoL). Both of these patients were engaged in a 12 weeks period of daily HAL®-supported locomotion training. In addition to improvements in motor functions and walking abilities, both show significant reduction in pain severity and improvements in all HRQoL domains. Although various causal factors likely contribute to abatement of CNP, the reported results occurred due to a new approach in the rehabilitation of chronic spinal cord injury patients. These findings suggest not only the feasibility of this new approach but in conclusion, demonstrate the effectiveness of neurologic controlled locomotion training in the long-term management of refractory neuropathic pain. Implications for Rehabilitation CNP remains a challenge in the rehabilitation of chronic SCI patients. Locomotion training with the HAL exoskeleton seems to improve CNP

  7. Tramadol for neuropathic pain in adults.

    Science.gov (United States)

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

    2017-06-15

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

  8. Regulation of Neurotrophin-3 and Interleukin-1β and Inhibition of Spinal Glial Activation Contribute to the Analgesic Effect of Electroacupuncture in Chronic Neuropathic Pain States of Rats

    Directory of Open Access Journals (Sweden)

    Wenzhan Tu

    2015-01-01

    Full Text Available Growing evidence indicates that neurotrophin-3, interleukin-1β, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1β in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL-1β. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1β production and spinal glial activity.

  9. Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain.

    Science.gov (United States)

    Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

    2017-09-01

    Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system. In recent years, accumulating studies have revealed the expression, distribution and function of chemokines in the spinal cord under chronic pain conditions. In this review, we provide evidence showing that several chemokines are upregulated after peripheral nerve injury and contribute to the pathogenesis of neuropathic pain via different forms of neuron-glia interaction in the spinal cord. First, chemokine CX3CL1 is expressed in primary afferents and spinal neurons and induces microglial activation via its microglial receptor CX3CR1 (neuron-to-microglia signaling). Second, CCL2 and CXCL1 are expressed in spinal astrocytes and act on CCR2 and CXCR2 in spinal neurons to increase excitatory synaptic transmission (astrocyte-to-neuron signaling). Third, we recently identified that CXCL13 is highly upregulated in spinal neurons after spinal nerve ligation and induces spinal astrocyte activation via receptor CXCR5 (neuron-to-astrocyte signaling). Strategies that target chemokine-mediated neuron-glia interactions may lead to novel therapies for the treatment of neuropathic pain.

  10. 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...

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

    Directory of Open Access Journals (Sweden)

    Shaygan M

    2014-05-01

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

  12. 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

  13. The efficacy and safety of pregabalin in the treatment of neuropathic pain associated with chronic lumbosacral radiculopathy.

    NARCIS (Netherlands)

    Baron, R.; Freynhagen, R.; Tolle, T.R.; Cloutier, C.; Leon, T.; Murphy, T.K.; Phillips, K.; Vissers, K.C.P.; et al.,

    2010-01-01

    We evaluated the efficacy of pregabalin in patients with chronic lumbosacral radiculopathy. This randomized, controlled, withdrawal trial included five phases: screening (4-18 days); run-in (4-10 days) to screen out placebo responders; single-blind (28 days) to identify pregabalin responders;

  14. Tinnitus sensitization: Sensory and psychophysiological aspects of a new pathway of acquired centralization of chronic tinnitus.

    Science.gov (United States)

    Zenner, Hans P; Pfister, Markus; Birbaumer, Niels

    2006-12-01

    Acquired centralized tinnitus (ACT) is the most frequent form of chronic tinnitus. The proposed ACT sensitization (ACTS) assumes a peripheral initiation of tinnitus whereby sensitizing signals from the auditory system establish new neuronal connections in the brain. Consequently, permanent neurophysiological malfunction within the information-processing modules results. Successful treatment has to target these malfunctioning information processing. We present in this study the neurophysiological and psychophysiological aspects of a recently suggested neurophysiological model, which may explain the symptoms caused by central cognitive tinnitus sensitization. Although conditioned reflexes, as a causal agent of chronic tinnitus, respond to extinction procedures, sensitization may initiate a vicious circle of overexcitation of the auditory system, resisting extinction and habituation. We used the literature database as indicated under "References" covering English and German works. For the ACTS model we extracted neurophysiological hypotheses of the auditory stimulus processing and the neuronal connections of the central auditory system with other brain regions to explain the malfunctions of auditory information processing. The model does not assume information-processing changes specific for tinnitus but treats the processing of tinnitus signals comparable with the processing of other external stimuli. The model uses the extensive knowledge available on sensitization of perception and memory processes and highlights the similarities of tinnitus with central neuropathic pain. Quality, validity, and comparability of the extracted data were evaluated by peer reviewing. Statistical techniques were not used. According to the tinnitus sensitization model, a tinnitus signal originates (as a type I-IV tinnitus) in the cochlea. In the brain, concerned with perception and cognition, the 1) conditioned associations, as postulated by the tinnitus model of Jastreboff, and the 2

  15. Effectiveness of pregabalin for the treatment of chronic low back pain with accompanying lower limb pain (neuropathic component: a non-interventional study in Japan

    Directory of Open Access Journals (Sweden)

    Taguchi T

    2015-08-01

    Full Text Available Toshihiko Taguchi,1 Ataru Igarashi,2 Stephen Watt,3 Bruce Parsons,3 Alesia Sadosky,3 Kazutaka Nozawa,4 Kazuhiro Hayakawa,4 Tamotsu Yoshiyama,4 Nozomi Ebata,4 Koichi Fujii4 1Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 3Pfizer Inc., New York, NY, USA; 4Pfizer Japan, Inc., Tokyo, Japan Objective: To evaluate the impact of pregabalin on sleep, pain, function, and health status in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP under routine clinical practice. Methods: This prospective, non-interventional, observational study enrolled Japanese adults (≥18 years with CLBP-NeP of duration ≥3 months and severity ≥5 on a numerical rating scale (0= no pain, 10= worst possible pain. Treatment was 8 weeks with pregabalin (n=157 or usual care alone (n=174; choice of treatment was determined by the physician. The primary efficacy outcome was change from baseline to 8 weeks in pain-related interference with sleep, assessed using the Pain-Related Sleep Interference Scale (PRSIS; 0= did not interfere with sleep, 10= completely interferes with sleep. Secondary endpoints were changes in PRSIS at week 4, and changes at weeks 4 and 8 in pain (numerical rating scale, function (Roland-Morris Disability Questionnaire, and quality of life (EuroQol 5D-5L; global assessments of change were evaluated from the clinician and patient perspectives at the final visit. Results: Demographic characteristics were similar between cohorts, but clinical characteristics suggested greater disease severity in the pregabalin group including a higher mean (standard deviation pain score, 6.3 (1.2 versus 5.8 (1.1 (P<0.001. For the primary endpoint, pregabalin resulted in significantly greater improvements in PRSIS at week 8, least-squares mean changes of -1.3 versus

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

    Directory of Open Access Journals (Sweden)

    Abolfazl Abbaszadeh

    2018-02-01

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

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

    Science.gov (United States)

    Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

    2017-01-01

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

  18. 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

    significant (P idea that peripheral neuropathic pain is primarily driven from damaged nerve endings in the periphery, while chronic fibromyalgia pain may be a central disorder with increased activity in pain-facilitating systems.

  19. [Management of neuropathic pain].

    Science.gov (United States)

    Lozeron, P; Kubis, N

    2015-07-01

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

  20. Central Blood Pressure and Chronic Kidney Disease Progression

    Directory of Open Access Journals (Sweden)

    Debbie L. Cohen

    2011-01-01

    Full Text Available Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.

  1. 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

  2. Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

    Science.gov (United States)

    Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

    2013-01-01

    Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

  3. Neuroimmune-Driven Neuropathic Pain Establishment: A Focus on Gender Differences

    Directory of Open Access Journals (Sweden)

    Vincenzo Coraggio

    2018-01-01

    Full Text Available The role of neuroinflammatory cells in the establishment of neuropathic pain has been investigated in depth in the last few years. In particular, microglia have been shown to be key players in the induction of tactile allodynia, as they release proinflammatory molecules that, in turn, sensitize nociceptive neurons within the spinal cord. However, the role of peripheral immune cells such as macrophages, infiltrating monocytes, mast cells, and T-cells has been highlighted in the last few studies, even though the data are still conflicting and need to be clarified. Intriguingly, the central (microglia and peripheral (T-cell-adaptive immune cells that orchestrate maladaptive process-driven neuropathic pain seem to be involved in a gender-dependent manner. In this review, we highlight the role of the microglia and peripheral immune cells in chronic degenerative disease associated with neuro-immune-inflammatory processes.

  4. Cortical and white matter alterations in patients with neuropathic pain after spinal cord injury.

    Science.gov (United States)

    Yoon, Eun Jin; Kim, Yu Kyeong; Shin, Hyung Ik; Lee, Youngjo; Kim, Sang Eun

    2013-12-02

    Neuropathic pain is one of the major problems of patients with spinal cord injury (SCI), which remains refractory to treatment despite a variety of therapeutic approach. Multimodal neuroimaging could provide complementary information for brain mechanisms underlying neuropathic pain, which could be based on development of more effective treatment strategies. Ten patients suffering from chronic neuropathic pain after SCI and 10 healthy controls underwent FDG-PET, T1-anatomical MRI and diffusion tensor imaging. We found decreases of both metabolism and the gray matter volume in the left dorsolateral prefrontal cortex in patients compared to healthy controls, as well as hypometabolism in the medial prefrontal cortex and gray matter volume loss in bilateral anterior insulae and subgenual anterior cingulate cortices. These brain regions are generally known to participate in pain modulation by affective and cognitive processes. Decreases of mean diffusivity (MD) in the right internal capsule including, cerebral peduncle, pre-and post-central white matter, and prefrontal white matter as components of the corticospinal and thalamocortical tracts were demonstrated in patients. Further, lower MD value of prefrontal white matter was correlated with decreased metabolism of medial prefrontal cortex in patients. These results indicated that white matter changes imply abnormal pain modulation in patients as well as motor impairment. Our study showed the functional and structural multimodal imaging modality commonly identified the possible abnormalities in the brain regions participating pain modulation in neuropathic pain. Multifaceted imaging studies in neuropathic pain could be useful elucidating precise mechanisms of persistent pain, and providing future directions for treatment. © 2013 Elsevier B.V. All rights reserved.

  5. Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

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    Ma Fei

    2012-12-01

    Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

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

    OpenAIRE

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

    2014-01-01

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

  7. Methodology for self-report of rest pain (or spontaneous pain) vs evoked pain in chronic neuropathic conditions: a prospective observational pilot study

    OpenAIRE

    He, David; Grant, Brian; Holden, Ronald R.; Gilron, Ian

    2017-01-01

    Abstract. Introduction:. The distinction between pain at rest and pain evoked by touch or movement has important clinical implications and may be associated with different mechanisms. However, current methods of clinical pain assessment pay little attention to directly distinguishing between these contrasting components of symptom burden. Objectives:. We developed the 10-item “Functional Impact of Neuropathic Evoked and Spontaneous Symptom Evaluation” questionnaire designed to distinguish ...

  8. Neuropathic pain in primary care

    African Journals Online (AJOL)

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

  9. 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-...

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

    Directory of Open Access Journals (Sweden)

    Taraneh Moini Zanjani

    2013-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Kelly Barbosa Gama

    2018-01-01

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

  12. Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: a review.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Leis, Stefan; Höller, Peter; Thon, Natasha; Thomschewski, Aljoscha; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2014-01-01

    Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain. To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy. A MEDLINE search was performed using following terms: "Spinal cord injury", "Neuropathic pain", "Brain stimulation", "Deep brain stimulation" (DBS), "Motor cortex stimulation" (MCS), "Transcranial magnetic stimulation" (TMS), "Transcranial direct current stimulation" (tDCS), "Cranial electrotherapy stimulation" (CES). Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation - tDCS - applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI. A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Central arterial characteristics of gout patients with chronic kidney diseases.

    Science.gov (United States)

    Celik, Gulperi; Yilmaz, Sema; Kebapcilar, Levent; Gundogdu, Ali

    2017-05-01

    The aim of this study was to investigate the relationship between central blood pressure, arterial stiffness parameters and renal function parameters in gout patients with chronic kidney disease (CKD) and without CKD. The study enrolled 48 gout patients and 32 control subjects. Central blood pressure, arterial stiffness parameters and renal function parameters in gout patients were investigated. The vascular measurements were performed with an arteriograph. Of the gout patients, 40.1% had CKD. The 24-h pulse pressure (PP) (P < 0.001), central systolic blood pressure (SBP) (P < 0.001), central diastolic blood pressure (DBP) (P < 0.001), cardiac output (CO) (P < 0.001) and peripheral resistance (P = 0.004) were significantly higher in the all patients with gout compared to healthy control subjects. Moreover, when the gout patients with and without CKD were compared, the gout patients with CKD had higher 24-h PP (P = 0.009), 24-h augmentation index standardized to a heart rate of 75 beats per min (AIx@75) (P < 0.023), daytime PP (P = 0.001), daytime AIx@75 (P = 0.027), and nighttime PP (P = 0.035) than the gout patients without CKD. In our study, gout patients with CKD had worse and more emphasized evidence of arterial stiffness than gout patients without CKD. Further investigations with large sample sizes are needed to evaluate the effect of CKD on the arterial stiffness of gout patients. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  15. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Buscher, H.C.J.L.; Goor, H. van; Wilder-Smith, O.H.G.

    2011-01-01

    BACKGROUND AND OBJECTIVES: : Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain

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

    Science.gov (United States)

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

    2015-05-01

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

  17. Bilateral chylothorax in a patient with chronic central vein thrombosis and chronic thromboembolic pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Avdhesh Bansal

    2015-01-01

    Full Text Available The chylothorax is not a common presentation, and bilateral chylothorax in patients with chronically high central venous pressure secondary to venous thrombosis is a rare in incidence. We reported a case of bilateral chylothorax in a patient of chronic deep vein thrombosis (DVT in central veins with chronic thromboembolic pulmonary hypertension who presented with 2 weeks history of increased breathlessness, bilateral chest discomfort and weakness. Work-up with chest X-ray and ultrasonography-chest showed gross left sided and mild right sided pleural effusion, thoracocentesis was consistent with chylothorax. Contrast enhanced computed tomography-chest showed multiple collateral formation of left side subclavian vein, venous Doppler showed old DVT in right and left subclavian veins and two-dimensional echocardiogram showed finding of severe pulmonary hypertension. After 24 h of fasting and conservative management, pleural drain became clear and decreased in the amount. Patient′s video assisted thoracoscopic surgery was done, and thoracic duct was ligated and cut down at diaphragmatic level and bilateral talc pleurodesis done. Patient improved clinically and radiologically.

  18. Efficacy and tolerability balance of oxycodone/naloxone and tapentadol in chronic low back pain with a neuropathic component: a blinded end point analysis of randomly selected routine data from 12-week prospective open-label observations.

    Science.gov (United States)

    Ueberall, Michael A; Mueller-Schwefe, Gerhard H H

    2016-01-01

    To evaluate the benefit-risk profile (BRP) of oxycodone/naloxone (OXN) and tapentadol (TAP) in patients with chronic low back pain (cLBP) with a neuropathic component (NC) in routine clinical practice. This was a blinded end point analysis of randomly selected 12-week routine/open-label data of the German Pain Registry on adult patients with cLBP-NC who initiated an index treatment in compliance with the current German prescribing information between 1st January and 31st October 2015 (OXN/TAP, n=128/133). Primary end point was defined as a composite of three efficacy components (≥30% improvement of pain, pain-related disability, and quality of life each at the end of observation vs baseline) and three tolerability components (normal bowel function, absence of either central nervous system side effects, and treatment-emergent adverse event [TEAE]-related treatment discontinuation during the observation period) adopted to reflect BRP assessments under real-life conditions. Demographic as well as baseline and pretreatment characteristics were comparable for the randomly selected data sets of both index groups without any indicators for critical selection biases. Treatment with OXN resulted formally in a BRP noninferior to that of TAP and showed a significantly higher primary end point response vs TAP (39.8% vs 25.6%, odds ratio: 1.93; P =0.014), due to superior analgesic effects. Between-group differences increased with stricter response definitions for all three efficacy components in favor of OXN: ≥30%/≥50%/≥70% response rates for OXN vs TAP were seen for pain intensity in 85.2%/67.2%/39.1% vs 83.5%/54.1%/15.8% ( P = ns/0.031/<0.001), for pain-related disability in 78.1%/64.8%/43.8% vs 66.9%/50.4%/24.8% ( P =0.043/0.018/0.001), and for quality of life in 76.6%/68.0%/50.0% vs 63.9%/54.1%/34.6% ( P =0.026/0.022/0.017). Overall, OXN vs TAP treatments were well tolerated, and proportions of patients who either maintained a normal bowel function (68.0% vs 72

  19. Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

    Science.gov (United States)

    Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

    2012-01-01

    Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

  20. 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

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

    Science.gov (United States)

    Mcmonnies, Charles W

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

  2. Dor neuropática central após lesão medular traumática: capacidade funcional e aspectos sociais Dolor neuropático central después de lesión medular traumática: capacidad funcional y aspectos sociales Central neuropathic pain after traumatic spinal cord injury: functional capacity and social aspects

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    Janaina Vall

    2005-12-01

    Full Text Available Estudo de caso comparativo com o objetivo de avaliar a capacidade funcional e os aspectos sociais de dois pacientes, ambos com lesão medular traumática, sem e com dor neuropática central associada, respectivamente. Para avaliar a capacidade funcional, foi utilizado como instrumento o Functional Independence Measure ou Escala de Independência Funcional. E para avaliar os aspectos sociais foi construído o ecomapa de cada paciente, preconizado pelo modelo Calgary de avaliação de famílias. Ambos foram aplicados no domicílio do paciente. Os resultados mostraram que o paciente com dor neuropática central secundária à lesão medular possui baixa capacidade funcional e precária rede social de apoio, quando comparado com o paciente com as mesmas condições, porém sem dor associada.Estudio de caso comparativo con el objetivo de evaluar la capacidad funcional y los aspectos sociales de dos paciente, ambos con lesión medular traumática, sin y con el dolor neuropático central, respectivamente. Para evaluar la capacidad funcional, se usó como instrumento la Escala de Independencia Funcional. Y para evaluar los aspectos sociales, el ecomapa de cada paciente fue construido, preconizado por el modelo Calgary de evaluación de familias. Los dos furon aplicados en la casa del paciente. Los resultados mostraron que el paciente con dolor neuropatico central secundario a la lesión medular posee capacidad funcional baja y precaria red social de apoyo, cuando comparado con el paciente con las mismas condiciones, pero sin el dolor asociado.Comparative study of case with the aim of evaluating the functional capacity and social aspects of two patients, both with traumatic spinal cord injury, without and with central neuropathic pain associated, respectively. To evaluate the functional capacity it was used as instrument Functional Independence Measure. And to evaluate the social aspects the ecomap of each patient one it was built, extolled by the model

  3. Role of microglia in neuropathic pain, postoperative pain, and morphine tolerance

    Science.gov (United States)

    Wen, Yeong-Ray; Tan, Ping-Heng; Cheng, Jen-Kun; Liu, Yen-Chin; Ji, Ru-Rong

    2011-01-01

    Management of chronic pain such as nerve injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer is a real clinical challenge. Major surgeries such as breast and thoracic surgery, leg amputation, and coronary artery bypass surgery also lead to chronic pain in 10–50% of individuals after acute postoperative pain, in part due to surgery-induced nerve injury. Current treatments mainly focus on blocking neurotransmission in the pain pathway and have only resulted in limited success. Ironically, chronic opioid exposure may lead to paradoxical pain. Development of effective therapeutic strategies requires a better understanding of cellular mechanisms underlying the pathogenesis of neuropathic pain. An important progress in pain research points to important role of microglial cells in the development of chronic pain. Spinal cord microglia are strongly activated after nerve injury, surgical incision, and chronic opioid exposure. Increasing evidence suggests that under all these conditions the activated microglia not only exhibit increased expression of microglial markers CD11b and Iba1 but also display elevated phosphorylation of p38 MAP kinase. Inhibition of spinal cord p38 has been shown to attenuate neuropathic pain and postoperative pain, as well as morphine-induced antinociceptive tolerance. Activation of p38 in spinal microglia results in increased synthesis and release of the neurotrophin BDNF and the proinflammatory cytokines IL-1β, IL-6, and TNF-α. These microglia-released mediators can powerfully modulate spinal cord synaptic transmission, leading to increased excitability of dorsal horn neurons, i.e. central sensitization, in part via suppressing inhibitory synaptic transmission. We review the studies that support the pronociceptive role of microglia in conditions of neuropathic pain, post-surgical pain, and opioid tolerance. Some of these studies have been accomplished by four Taiwanese anesthesiologists who are also

  4. Proteomic Identification of an Upregulated Isoform of Annexin A3 in the Spinal Cords of Rats in a Neuropathic Pain Model

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    Wangyuan Zou

    2017-09-01

    Full Text Available Neuropathic pain (NP is induced by nerve damage or a disturbance in the peripheral or central nervous systems. Nerve damage causes the activation of sensitizing mechanisms in the peripheral and central nervous systems, which induces transcriptional and post-transcriptional alterations in sensory nerves. However, the underlying mechanisms of NP remain elusive. In the study, Two-dimensional gel electrophoresis (2DGE-based comparative proteomics identified 38 differential gel spots, and 15 differentially expressed proteins (DEPs between the sham and the chronic constriction injury (CCI-induced neuropathic pain rats. Of them, Annexin A3 (ANXA3 was significantly increased after CCI with Western blot analysis and immunofluorescence imaging. A lentivirus delivering ANXA3 shRNA (LV-shANXA3 was administered intrathecally to determine the analgesic effects of ANXA3 on allodynia and hyperalgesia in a CCI-induced neuropathic pain model in rats. Further study showed that LV-shANXA3 reversed the upregulation of ANXA3, alleviated CCI-induced mechanical allodynia and thermal hyperalgesia. The study indicated that ANXA3 may play an important role in neuropathic pain.

  5. The role of glia in the spinal cord in neuropathic and inflammatory pain.

    Science.gov (United States)

    Old, Elizabeth Amy; Clark, Anna K; Malcangio, Marzia

    2015-01-01

    Chronic pain, both inflammatory and neuropathic, is a debilitating condition in which the pain experience persists after the painful stimulus has resolved. The efficacy of current treatment strategies using opioids, NSAIDS and anticonvulsants is limited by the extensive side effects observed in patients, underlining the necessity for novel therapeutic targets. Preclinical models of chronic pain have recently provided evidence for a critical role played by glial cells in the mechanisms underlying the chronicity of pain, both at the site of damage in the periphery and in the dorsal horn of the spinal cord. Here microglia and astrocytes respond to the increased input from the periphery and change morphology, increase in number and release pro-nociceptive mediators such as ATP, cytokines and chemokines. These gliotransmitters can sensitise neurons by activation of their cognate receptors thereby contributing to central sensitization which is fundamental for the generation of allodynia, hyperalgesia and spontaneous pain.

  6. Tapentadol extended-release for treatment of chronic pain: a review

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    Vadivelu N

    2011-08-01

    Full Text Available Nalini Vadivelu1, Alexander Timchenko1, Yili Huang2, Raymond Sinatra11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USAAbstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine

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

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    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.

  8. Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

    Science.gov (United States)

    Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

    2011-05-01

    Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

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

    Science.gov (United States)

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

    2017-09-14

    Neuropathic pain, which is due to nerve disease or damage, represents a significant burden on people and society. It can be particularly unpleasant and achieving adequate symptom control can be difficult. Non-pharmacological methods of treatment are often employed by people with neuropathic pain and may include transcutaneous electrical nerve stimulation (TENS). This review supersedes one Cochrane Review 'Transcutaneous electrical nerve stimulation (TENS) for chronic pain' (Nnoaham 2014) and one withdrawn protocol 'Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults' (Claydon 2014). This review replaces the original protocol for neuropathic pain that was withdrawn. To determine the analgesic effectiveness of TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. We searched CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, Web of Science, PEDro, LILACS (up to September 2016) and various clinical trials registries. We also searched bibliographies of included studies for further relevant studies. We included randomised controlled trials where TENS was evaluated in the treatment of central or peripheral neuropathic pain. We included studies if they investigated the following: TENS versus placebo (sham) TENS, TENS versus usual care, TENS versus no treatment and TENS in addition to usual care versus usual care alone in the management of neuropathic pain in adults. Two review authors independently screened all database search results and identified papers requiring full-text assessment. Subsequently, two review authors independently applied inclusion/exclusion criteria to these studies. The same review authors then independently extracted data, assessed for risk of bias using the Cochrane standard tool and rated the quality of evidence using GRADE. We included 15 studies with 724 participants. We found a

  10. The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Hannah L Pellkofer

    Full Text Available Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO. While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST following the protocol of the German Research Network on Neuropathic Pain (DFNS. Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11 suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG. These data emphasize the high prevalence of neuropathic pain and hyperalgesia

  11. Increase in Central Retinal Edema after Subthreshold Diode Micropulse Laser Treatment of Chronic Central Serous Chorioretinopathy

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    Maciej Gawęcki

    2015-01-01

    Full Text Available Purpose. Subthreshold diode micropulse laser (SDM treatment is believed to be safe method of treating clinical entities involving retinal edema. We present a case of serous edematous reaction of the retina to SDM treatment. Methods. Case report. Results. A patient with chronic central serous chorioretinopathy (CSCR was treated with SDM Yellow multispot laser. Procedure had been preceded by careful titration of the laser power, which after achieving of the threshold parameter was decreased by 50%. The follow-up visit two days after treatment revealed significant central retinal edema and subretinal fluid. Fundus autofluorescence image showed thermal reaction from the RPE in the form of small spots of hyperfluorescence corresponding to the laser multispot pattern used for treatment. Retinal edema resolved after topical bromfenac and single intravitreal bevacizumab injection. Slight pigmentary reaction from the RPE persisted. Conclusion. In the treatment of CSCR, there is a need to significantly reduce threshold SDM power parameters or simply use very low power without titration.

  12. Neuropathic pain and cytokines: current perspectives

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    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

  13. Central Hyperexcitability in Chronic Musculoskeletal Pain: A Conceptual Breakthrough with Multiple Clinical Implications

    Directory of Open Access Journals (Sweden)

    Jan Lidbeck

    2002-01-01

    Full Text Available Recent investigations of dysfunctional pain processing in the central nervous system have contributed much knowledge about the development of chronic musculoskeletal pain. Many common chronic musculoskeletal pain syndromes - including regional myofascial pain syndromes, whiplash pain syndromes, refractory work-related neck-shoulder pain, certain types of chronic low back pain, fibromyalgia and others - may essentially be explained by abnormalities in central pain modulation. The growing awareness of dysfunctional central pain modulation may be a conceptual breakthrough leading to a better understanding of common chronic pain disorders. A new paradigm will have multiple clinical implications, including re-evaluation of clinical practice routines and rehabilitation methods, and will focus on controversial issues of medicolegal concern. The concept of dysfunctional central pain processing will also necessitate a mechanism-based classification of pain for the selection of individual treatment and rehabilitation programs for subgroups of patients with chronic musculoskeletal pain due to different pathophysiological mechanisms.

  14. Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial

    NARCIS (Netherlands)

    Olesen, S.S.; Bouwense, S.A.W.; Wilder-Smith, O.H.G.; Goor, H. van; Drewes, A.M.

    2011-01-01

    BACKGROUND & AIMS: Pain is a disabling symptom for patients with chronic pancreatitis (CP) and difficult to treat. Evidence from basic science and human studies indicates that pain processing by the central nervous system is abnormal and resembles that observed in patients with neuropathic pain

  15. Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

    Science.gov (United States)

    Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

    2016-04-01

    Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

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

    OpenAIRE

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2018-05-18

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

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

    Science.gov (United States)

    Nicholson, Bruce D

    2003-12-01

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

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

    Science.gov (United States)

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

    2015-01-21

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

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

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    Ming Liu

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  2. Neuropathic pain management in children.

    LENUS (Irish Health Repository)

    Hyde, Catherine

    2012-10-01

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

  3. 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.

  4. 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

  5. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial.

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Olesen, S.S.; Drewes, A.M.; Poley, J.W.; Goor, H. van; Wilder-Smith, O.H.G.

    2012-01-01

    BACKGROUND: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect

  6. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial

    NARCIS (Netherlands)

    S.A.W. Bouwense (Stefan); S.S. Olesen (Søren); A.M. Drewes (Asbjørn); J.-W. Poley (Jan-Werner); H. van Goor (Harry); O.H.G. Wilder-Smith (Oliver)

    2012-01-01

    textabstractBackground: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate

  7. The Impact of Enrollment in a Specialized Interdisciplinary Neuropathic Pain Clinic

    Directory of Open Access Journals (Sweden)

    Alex Garven

    2011-01-01

    Full Text Available BACKGROUND: Chronic pain clinics have been created because of the increasing recognition of chronic pain as a very common, debilitating condition that requires specialized care. Neuropathic pain (NeP is a multifaceted, specialized form of chronic pain that often requires input from multiple disciplines for assessment and management.

  8. Neuropathic pain and dry eye.

    Science.gov (United States)

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

    2018-01-01

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

  9. 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.

  10. Non-invasive Transcranial Magnetic Stimulation (TMS of the Motor Cortex for Neuropathic Pain—At the Tipping Point?

    Directory of Open Access Journals (Sweden)

    Roi Treister

    2013-10-01

    Full Text Available The term “neuropathic pain” (NP refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain’s surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS. Repeated sessions of many TMS pulses (rTMS can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include “frameless stereotactic” neuronavigation systems, in which patients’ head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials.

  11. Central and peripheral mechanisms in chronic tension-type headache

    OpenAIRE

    Lipchik, Gay L.; Holroyd, Kenneth A.; France, Christopher R.; Kvaal, Steven A.; Segal, David; Cordingley, Gary E.; Rokicki, Lori A.; McCool, Heidi R.

    1996-01-01

    The second exteroceptive suppression of masseter muscle activity (ES2) and tenderness in pericranial muscles were evaluated in 112 young adults who met IHS criteria in the following diagnostic classifications: 31 chronic tension headache, 31 episodic tension headache, 33 migraine without aura and 17 migraine with aura. An additional 31 subjects served as controls. Pericranial muscle tenderness better distinguished diagnostic subgroups and better distinguished recurrent headache sufferers from...

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

    Science.gov (United States)

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

    2013-02-05

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

  13. Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy.

    Science.gov (United States)

    Altmann, Christine; Hardt, Stefanie; Fischer, Caroline; Heidler, Juliana; Lim, Hee-Young; Häussler, Annett; Albuquerque, Boris; Zimmer, Béla; Möser, Christine; Behrends, Christian; Koentgen, Frank; Wittig, Ilka; Schmidt, Mirko H H; Clement, Albrecht M; Deller, Thomas; Tegeder, Irmgard

    2016-12-01

    Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confirmed in primary sensory neurons. Autophagy and survival were impaired in progranulin-deficient neurons and improved in progranulin overexpressing neurons. Nerve injury in vivo caused an accumulation of LC3b-EGFP positive bodies in neurons of the dorsal root ganglia and nerves suggesting an impairment of autophagic flux. Overexpression of progranulin in these neurons was associated with a reduction of the stress marker ATF3, fewer protein aggregates in the injured nerve and enhanced stump healing. At the behavioral level, further inhibition of the autophagic flux by hydroxychloroquine intensified cold and heat nociception after sciatic nerve injury and offset the pain protection provided by progranulin. We infer that progranulin may assist in removal of protein waste and thereby helps to resolve neuropathic pain after nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Central pain processing in chronic tension-type headache

    DEFF Research Database (Denmark)

    Lindelof, Kim; Ellrich, Jens; Jensen, Rigmor

    2009-01-01

    OBJECTIVE: Chronic tension-type headache (CTTH) affects 3% of the population. Directly and indirectly it causes high costs and considerable loss of quality of life. The mechanisms of this disorder are poorly understood and the treatment possibilities are therefore limited. The blink reflex (BR......) reflects neuronal excitability due to nociceptive input in the brainstem. The aim of this study was to investigate nociceptive processing at the level of the brainstem in an experimental pain model of CTTH symptoms. METHODS: The effect of conditioning pain, 5 min infusion of hypertonic saline into the neck...... muscles, was investigated in 20 patients with CTTH and 20 healthy controls. In addition, a pilot study with isotonic saline was performed with 5 subjects in each group. The BR was elicited by electrical stimuli with an intensity of four times the pain threshold, with a superficial concentric electrode. We...

  15. Pharmacologic management of neuropathic pain.

    Science.gov (United States)

    Gordon, Debra B; Love, Georgette

    2004-12-01

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

  16. Pharmacological treatment of diabetic neuropathic pain.

    Science.gov (United States)

    Smith, Howard S; Argoff, Charles E

    2011-03-26

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

  17. Quantitative sensory testing of neuropathic pain patients: potential mechanistic and therapeutic implications.

    Science.gov (United States)

    Pfau, Doreen B; Geber, Christian; Birklein, Frank; Treede, Rolf-Detlef

    2012-06-01

    Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.

  18. Chronic Central Serous Chorioretinopathy in a Patient with Pigment Dispersion Syndrome: A Possible Correlation.

    Science.gov (United States)

    Kourkoutas, Dimitrios; Tsakonas, George; Karamaounas, Aristotelis; Karamaounas, Nikolaos

    2017-01-01

    Chronic central serous chorioretinopathy (CSCR) is a progressive chorioretinopathy with widespread atrophic RPE abnormalities and serous retinal detachments (SRDs) present for 6 months or longer. We report a case of CSCR in a 38-year-old patient with Pigment Dispersion Syndrome (PDS). In the presented case of CSCR, the chronic course of the disease may in part be associated with an underlying generalized degenerative dysfunction of the pigmented cells of the eye on grounds of PDS. We suggest that a chronic course of disease may be suspected in the setting of CSCR with concurrent RPE pathology, such as what is found in PDS.

  19. Chronic Central Serous Chorioretinopathy in a Patient with Pigment Dispersion Syndrome: A Possible Correlation

    Directory of Open Access Journals (Sweden)

    Dimitrios Kourkoutas

    2017-01-01

    Full Text Available Chronic central serous chorioretinopathy (CSCR is a progressive chorioretinopathy with widespread atrophic RPE abnormalities and serous retinal detachments (SRDs present for 6 months or longer. We report a case of CSCR in a 38-year-old patient with Pigment Dispersion Syndrome (PDS. In the presented case of CSCR, the chronic course of the disease may in part be associated with an underlying generalized degenerative dysfunction of the pigmented cells of the eye on grounds of PDS. We suggest that a chronic course of disease may be suspected in the setting of CSCR with concurrent RPE pathology, such as what is found in PDS.

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

    Science.gov (United States)

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

    2016-04-01

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

  1. 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.

  2. Neuropathic pain: is quantitative sensory testing helpful?

    Science.gov (United States)

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

    2012-08-01

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

  3. 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.

  4. Depression in chronic respiratory disorders in a tertiary rural hospital of Central India

    Institute of Scientific and Technical Information of China (English)

    Sameer singhal; Pankaj Banode; Nitish Baisakhiya

    2009-01-01

    Objective: To determine prevalence of depression in chronic respiratory disorders in a tertiary rural hospital of Central India. Various studies done in past have shown that prevalence of depression in diabetes and hypertension is around 40%-57%. Few studies have been done to screen depression in chronic respiratory disorders. This study was conducted in a tertiary rural hospital of Central India to find out prevalence of depression in indoor patients suffering from chronic respiratory disorders. Methods: Total 68 patients were evaluated for depression. Patients suffering from chronic respiratory disorders (total duration of illness >3 months) were evaluated using Prime MD Questionnaire. Patients suffering from diabetes, heart diseases, stroke, having past history of psychiatric illness, drug abusers, having lack of social support and suffering from chronic upper respiratory tract infections were excluded from this study. Questionnaire was asked when treatment for acute phase of illness is over. Results: Out of 68 patients evaluated, 36 (53%) were found out to be suffering from depression. Female gender (80%) was more prone to depression, inspite of the fact that all alcoholics were male. 39% of all chronic obstructive pulmonary disease (COPD) patients were suffering from depression in comparison to 65% for pulmonary tuberculosis and 44% for other chronic respiratory illness. 54% of patients suffering from depression are 60 yrs of age, suggesting that age has no relation with depression. No association was seen between alcoholism and depression. Conclusion: Prevalence of depression in patients of chronic respiratory illness is very high, like in cases of diabetes and hypertension. Further community and hospital based studies are needed to find out exact prevalence of depression in chronic respiratory illnesses.

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

    Directory of Open Access Journals (Sweden)

    Hong Liu

    2015-03-01

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

  6. TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States

    Directory of Open Access Journals (Sweden)

    Laura Batti

    2016-06-01

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

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

    Science.gov (United States)

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

    2013-08-01

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

  8. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    Science.gov (United States)

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

    2013-01-01

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

  9. Combination treatment of neuropathic pain

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gui-Lin Jin

    2018-01-01

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

  11. Chronic central administration of Ghrelin increases bone mass through a mechanism independent of appetite regulation.

    Directory of Open Access Journals (Sweden)

    Hyung Jin Choi

    Full Text Available Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days. Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed, and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Philipp Bishay

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

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

    Science.gov (United States)

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

    2018-03-01

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

  18. Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

    Science.gov (United States)

    Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

    2007-04-01

    Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

  19. Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

    Science.gov (United States)

    Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

    2007-04-01

    Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

  20. The evidence for pharmacological treatment of neuropathic pain

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  2. Update on uncertain etiology of chronic kidney disease in Sri Lanka's north-central dry zone.

    Science.gov (United States)

    Wanigasuriya, Kamani

    2014-04-01

    This manuscript updates a review previously published in a local journal in 2012, about a new form of chronic kidney disease that has emerged over the past two decades in the north-central dry zone of Sri Lanka, where the underlying causes remain undetermined. Disease burden is higher in this area, particularly North Central Province, and affects a rural and disadvantaged population involved in rice-paddy farming. Over the last decade several studies have been carried out to estimate prevalence and identify determinants of this chronic kidney disease of uncertain etiology. Summarize the available evidence on prevalence, clinical profile and risk factors of chronic kidney disease of uncertain etiology in the north-central region of Sri Lanka. PubMed search located 16 manuscripts published in peer-reviewed journals. Three peer-reviewed abstracts of presentations at national scientific conferences were also included in the review. Disease prevalence was 5.1%-16.9% with more severe disease seen in men than in women. Patients with mild to moderate stages of disease were asymptomatic or had nonspecific symptoms; urinary sediments were bland; 24-hour urine protein excretion was urine, and mycotoxins detected in foods were below maximum statutory limits. Calcium-bicarbonate-type water with high levels of fluoride was predominant in endemic regions. Significantly high levels of cadmium in urine of cases compared to controls, as well as the disease's dose-related response to these levels, has drawn attention to this element as a possible contributing factor. Familial clustering of patients is suggestive of a polygenic inheritance pattern comparable to that associated with diseases of multifactorial etiology. Available data suggest that chronic kidney disease of uncertain etiology is an environmentally acquired disease, but to date no definitive causal factor has been identified. Geographic distribution and research findings suggest a multifactorial etiology.

  3. The role of ketamine in the treatment of chronic cancer pain

    OpenAIRE

    ZGAIA, ARMEANA OLIMPIA; IRIMIE, ALEXANDRU; SANDESC, DOREL; VLAD, CATALIN; LISENCU, COSMIN; ROGOBETE, ALEXANDRU; ACHIMAS-CADARIU, PATRICIU

    2015-01-01

    Background and aim Ketamine is a drug used for the induction and maintenance of general anesthesia, for the treatment of postoperative and posttraumatic acute pain, and more recently, for the reduction of postoperative opioid requirements. The main mechanism of action of ketamine is the antagonization of N-methyl-D-aspartate (NMDA) receptors that are associated with central sensitization. In the pathogenesis of chronic pain and particularly in neuropathic pain, an important role is played by ...

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

    Science.gov (United States)

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

    2018-01-01

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

  5. Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect.

    Science.gov (United States)

    Filho, Paulo Ricardo Marques; Vercelino, Rafael; Cioato, Stefania Giotti; Medeiros, Liciane Fernandes; de Oliveira, Carla; Scarabelot, Vanessa Leal; Souza, Andressa; Rozisky, Joanna Ripoll; Quevedo, Alexandre da Silva; Adachi, Lauren Naomi Spezia; Sanches, Paulo Roberto S; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

    2016-01-04

    Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, PtDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, PtDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, PtDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels

  6. Spinal SIRT1 activation attenuates neuropathic pain in mice.

    Directory of Open Access Journals (Sweden)

    Haijun Shao

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

  7. Atypical vitelliform macular dystrophy misdiagnosed as chronic central serous chorioretinopathy: case reports

    Directory of Open Access Journals (Sweden)

    Lee Young

    2012-07-01

    Full Text Available Abstract Background To report two cases of atypical vitelliform macular dystrophy misdiagnosed as chronic central serous chorioretinopathy. Case presentation Two patients with incidentally discovered abnormalities of the retina without specific symptoms were referred to our hospital for consultation. Bilateral macula atrophic lesions were observed and optical coherence tomography revealed serous retinal detachment in the macula. Fluorescein angiography showed multiple leakages around the central hypofluorescent area and indocyanine green angiography showed partially dilated choroidal vessels. Fundus autofluorescence (FAF showed a decreasing pattern of autofluorescence in the subretinal fluid area, and increasing autofluorescence at the border of the serous retinal detachment. Both patients were diagnosed with chronic central serous chorioretinopathy. Photodynamic therapy and intravitreal bevacizumab injection were administered for engorged choroidal vessels during follow-up, but neither patient showed improvement in symptoms or ophthalmologic findings. Based on re-evaluation by fundus photography, optical coherence tomography, fluorescein angiography, and comparison of the results of FAF with the first visit, vitelliform macular dystrophy was suspected and a definite diagnosis was made by electrooculography and genetic testing. Conclusion In patients with continuous serous retinal detachment without response to photodynamic therapy or intravitreal bevacizumab injection, careful fundus exam and FAF can be used to diagnose atypical vitelliform macular dystrophy.

  8. Chronic central serous choroidopathy with severe visual loss in hyperopic microphthalmic identical twins

    Directory of Open Access Journals (Sweden)

    Fabry, Annelies

    2011-01-01

    Full Text Available Objective: To report chronic central serous choroidopathy with severe visual loss in hyperopic microphthalmic identical twins. Methods: The index patient was first examined in 1994, at age 31, and has been followed up closely for 17 years. He had repeated fluorescein and indocyanine green angiograms, OCT, ultrasound biometry, and recently also autofluorescence and EDI OCT. His twin brother was first examined in 2010, at age 47, and had a similar extensive exploration. Results: The index patient had a mean refractive error of +6 D OU and VA was 20/32++ in the RE and 20/200 in the LE in 1994. Vision slowly went down to 20/800+ in the RE and 20/600 in the LE in 2011. His twin brother has a mean refractive error of +6 D OU and VA 20/400 OU. Both have a short axial length of the eye, a thick choroid with dilated vessels, and central serous choroidopathy with cystic degeneration of the macula and retina in the posterior pole. Conclusions: We add to the reported complications of microphthalmos, chronic central serous choroidopathy.

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

    Science.gov (United States)

    Dugan, Elizabeth A; Sagen, Jacqueline

    2015-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Helder eCardoso-Cruz

    2011-08-01

    Full Text Available It is known that the thalamocortical loop plays a crucial role in the encoding of sensory-discriminative features of painful stimuli. However, only a few studies have addressed the changes in thalamocortical dynamics that may occur after the onset of chronic pain. Our goal was to evaluate how the induction of chronic neuropathic pain affected the flow of information within the thalamocortical loop throughout the brain states of the sleep-wake cycle. To address this issue we recorded local field potentials – LFPs – both before and after the establishment of neuropathic pain in awake freely moving adult rats chronically implanted with arrays of multielectrodes in the lateral thalamus and primary somatosensory cortex. Our results show that the neuropathic injury induced changes in the number of wake and slow-wave-sleep state episodes, and especially in the total number of transitions between brain states. Moreover, partial directed coherence – PDC – analysis revealed that the amount of information flow between cortex and thalamus in neuropathic animals decreased significantly, indicating that the overall thalamic activity had less weight over the cortical activity. However, thalamocortical LFPs displayed higher phase-locking during awake and slow-wave-sleep episodes after the nerve lesion, suggesting faster transmission of relevant information along the thalamocortical loop. The observed changes are in agreement with the hypothesis of thalamic dysfunction after the onset of chronic pain, and may result from diminished inhibitory effect of the primary somatosensory cortex over the lateral thalamus.

  11. Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system

    Science.gov (United States)

    Zhao, Xin; Wang, Chuang; Cui, Wu-Geng; Ma, Qing; Zhou, Wen-Hua

    2015-01-01

    Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain. PMID:25761874

  12. Neuropathic pain in spinal cord injury.

    Science.gov (United States)

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

    2013-01-01

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

  13. Interventional therapy for neuropathic pain

    Directory of Open Access Journals (Sweden)

    YANG Yang

    2013-10-01

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

  14. Treatment Sequencing in a Chronic Lymphocytic Leukemia Patient with Central Nervous System Involvement

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    Filipa Mousinho

    2018-01-01

    Full Text Available Early-stage chronic lymphocytic leukemia (CLL with neurologic involvement is a rare condition and should require a careful follow-up. Although no standard protocol exists for this condition, intrathecal chemotherapy, combined with systemic chemoimmunotherapy, has been used previously. This case describes the treatment of a patient with CLL and symptomatic compromise of the central nervous system. Our results suggest that a combination of chemotherapy, radiotherapy, and ibrutinib, administered sequentially over a 2-year period, led to a near-complete resolution of the cerebral spinal fluid neoplastic infiltration. Importantly, this response has been maintained with ibrutinib monotherapy for more than 12 months.

  15. Pain-related psychological distress, self-rated health and significance of neuropathic pain in Danish soldiers injured in Afghanistan

    DEFF Research Database (Denmark)

    Duffy, J R; Warburg, Finn; Koelle, S-F T

    2015-01-01

    BACKGROUND: Pain and mental health concerns are prevalent among veterans. While the majority of research has focused on chronic pain as an entity, there has been little work directed towards investigating the role of neuropathic pain in relation to psychological comorbidity. As such, we...... hypothesised that participants with signs of neuropathic pain would report higher levels of psychological distress and diminished self-rated health compared to those without a neuropathic component. METHODS: A retrospective review of standardised questionnaires (PainDETECT Questionnaire, Post-traumatic Stress...... pain. RESULTS: Fifty-three participants were included. The Post-traumatic Stress Disorder Checklist-Civilian score was in median (interquartile range) 26 (22-31), the Hospital Anxiety and Depression Scale score was 4 (2-6.5) and 2 (1-5) for anxiety and depression respectively. Evidence of neuropathic...

  16. Cervical radiofrequency neurotomy reduces central hyperexcitability and improves neck movement in individuals with chronic whiplash.

    Science.gov (United States)

    Smith, Ashley Dean; Jull, Gwendolen; Schneider, Geoff; Frizzell, Bevan; Hooper, Robert Allen; Sterling, Michele

    2014-01-01

    This study aims to determine if cervical medial branch radiofrequency neurotomy reduces psychophysical indicators of augmented central pain processing and improves motor function in individuals with chronic whiplash symptoms. Prospective observational study of consecutive patients with healthy control comparison. Tertiary spinal intervention centre in Calgary, Alberta, Canada. Fifty-three individuals with chronic whiplash associated disorder symptoms (Grade 2); 30 healthy controls. Measures were made at four time points: two prior to radiofrequency neurotomy, and 1- and 3-months post-radiofrequency neurotomy. Measures included: comprehensive quantitative sensory testing (including brachial plexus provocation test), nociceptive flexion reflex, and motor function (cervical range of movement, superficial neck flexor activity during the craniocervical flexion test). Self-report pain and disability measures were also collected. One-way repeated measures analysis of variance and Friedman's tests were performed to investigate the effect of time on the earlier measures. Differences between the whiplash and healthy control groups were investigated with two-tailed independent samples t-test or Mann-Whitney tests. Following cervical radiofrequency neurotomy, there were significant early (within 1 month) and sustained (3 months) improvements in pain, disability, local and widespread hyperalgesia to pressure and thermal stimuli, nociceptive flexor reflex threshold, and brachial plexus provocation test responses as well as increased neck range of motion (all P  0.13) was measured. Attenuation of psychophysical measures of augmented central pain processing and improved cervical movement imply that these processes are maintained by peripheral nociceptive input. Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Granovsky, Yelena

    2013-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Enrique J. Cobos

    2018-01-01

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

  19. Photodynamic therapy combined with antivascular endothelial growth factor treatment for recalcitrant chronic central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Asahi MG

    2017-11-01

    Full Text Available Masumi G Asahi,1 Andrew T Chon,1 Esmeralda Gallemore,1 Ron P Gallemore1,2 1Clinical Research Department, Retina Macula Institute, Torrance, CA, USA; 2Jules Stein Eye Institute, University of California, Los Angeles, CA, USA Purpose: To determine whether combination photodynamic therapy (PDT and antivascular endothelial growth factor (VEGF therapy is effective in the management of chronic central serous chorioretinopathy (CSC recalcitrant to conventional therapy. Methods: This was a retrospective analysis of eight patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were evaluated with a full ophthalmic examination, spectral-domain optical coherence tomography (OCT, fluorescein angiography (FA, and most with indocyanine green angiography (ICGA followed by treatment with half-fluence PDT and intravitreal anti-VEGF injection (seven bevacizumab, one aflibercept. Patients were seen in follow-up 1 month after treatment. Results: All eight patients achieved complete resolution in subretinal fluid following combination treatment. Average duration of CSC prior to initiation of combination therapy was 7.5 months. Mean central macular thickness on OCT decreased significantly from 401.2±52.7 µm to 297.9±18.2 µm (p=0.0010 by 4 months after treatment (1.63±1.18 months. Seven of eight patients were followed up for an average of 13 months with no recurrence during that time. One case recurred at 8 months and was treated with repeat combination at that time. Frank choroidal neovascularization (CNV was not identified in these cases on FA or ICGA studies. Eight of eight patients showed significant improvement in vision from a logMAR of 0.1125±0.099 to 0.0125±0.064 (p=0.019. Conclusion: Combination PDT and anti-VEGF is effective for chronic CSC which has failed conventional therapy. Associated CNV and/or inflammation may be reasons for greater success in

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

    Science.gov (United States)

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

    2015-01-01

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

  1. The neurosurgical treatment of neuropathic facial pain.

    Science.gov (United States)

    Brown, Jeffrey A

    2014-04-01

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

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

    NARCIS (Netherlands)

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

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

  3. 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.

  4. PHARMACOTHERAPY IN ELDERLY NEUROPATHIC PAIN

    Directory of Open Access Journals (Sweden)

    Thomas Eko P

    2013-10-01

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

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

    Science.gov (United States)

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

    2010-12-09

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

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

    Directory of Open Access Journals (Sweden)

    María del C. Rabí

    2010-12-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  8. Development and statistical optimization of nefopam hydrochloride loaded nanospheres for neuropathic pain using Box–Behnken design

    Directory of Open Access Journals (Sweden)

    S. Sukhbir

    2016-09-01

    Full Text Available Nefopam hydrochloride (NFH is a non-opioid centrally acting analgesic drug used to treat chronic condition such as neuropathic pain. In current research, sustained release nefopam hydrochloride loaded nanospheres (NFH-NS were auspiciously synthesized using binary mixture of eudragit RL 100 and RS 100 with sorbitan monooleate as surfactant by quasi solvent diffusion technique and optimized by 35 Box–Behnken designs to evaluate the effects of process and formulation variables. Fourier transform infrared spectroscopy (FTIR, differential scanning calorimetric (DSC and X-ray diffraction (XRD affirmed absence of drug–polymer incompatibility and confirmed formation of nanospheres. Desirability function scrutinized by design-expert software for optimized formulation was 0.920. Optimized batch of NFH-NS had mean particle size 328.36 nm ± 2.23, % entrapment efficiency (% EE 84.97 ± 1.23, % process yield 83.60 ± 1.31 and % drug loading (% DL 21.41 ± 0.89. Dynamic light scattering (DLS, zeta potential analysis and scanning electron microscopy (SEM validated size, charge and shape of nanospheres, respectively. In-vitro drug release study revealed biphasic release pattern from optimized nanospheres. Korsmeyer Peppas found excellent kinetics model with release exponent less than 0.45. Chronic constricted injury (CCI model of optimized NFH-NS in Wistar rats produced significant difference in neuropathic pain behavior (p < 0.05 as compared to free NFH over 10 h indicating sustained action. Long term and accelerated stability testing of optimized NFH-NS revealed degradation rate constant 1.695 × 10−4 and shelf-life 621 days at 25 ± 2 °C/60% ± 5% RH.

  9. Development and statistical optimization of nefopam hydrochloride loaded nanospheres for neuropathic pain using Box-Behnken design.

    Science.gov (United States)

    Sukhbir, S; Yashpal, S; Sandeep, A

    2016-09-01

    Nefopam hydrochloride (NFH) is a non-opioid centrally acting analgesic drug used to treat chronic condition such as neuropathic pain. In current research, sustained release nefopam hydrochloride loaded nanospheres (NFH-NS) were auspiciously synthesized using binary mixture of eudragit RL 100 and RS 100 with sorbitan monooleate as surfactant by quasi solvent diffusion technique and optimized by 3 5 Box-Behnken designs to evaluate the effects of process and formulation variables. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetric (DSC) and X-ray diffraction (XRD) affirmed absence of drug-polymer incompatibility and confirmed formation of nanospheres. Desirability function scrutinized by design-expert software for optimized formulation was 0.920. Optimized batch of NFH-NS had mean particle size 328.36 nm ± 2.23, % entrapment efficiency (% EE) 84.97 ± 1.23, % process yield 83.60 ± 1.31 and % drug loading (% DL) 21.41 ± 0.89. Dynamic light scattering (DLS), zeta potential analysis and scanning electron microscopy (SEM) validated size, charge and shape of nanospheres, respectively. In-vitro drug release study revealed biphasic release pattern from optimized nanospheres. Korsmeyer Peppas found excellent kinetics model with release exponent less than 0.45. Chronic constricted injury (CCI) model of optimized NFH-NS in Wistar rats produced significant difference in neuropathic pain behavior ( p  accelerated stability testing of optimized NFH-NS revealed degradation rate constant 1.695 × 10 -4 and shelf-life 621 days at 25 ± 2 °C/60% ± 5% RH.

  10. Hindfoot Arthrodesis for Neuropathic Deformity

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    Peng-Ju Huang

    2007-03-01

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

  11. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    Directory of Open Access Journals (Sweden)

    Bouwense SA

    2015-07-01

    -generating study provides the first evidence that pain relief with pregabalin is associated with anti-hyperalgesic effects and increased endogenous inhibitory modulation. No such effects were observed in patients experiencing pain relief with the placebo treatment. The mechanisms underlying analgesic response to placebo vs drug treatments are different and, together with their interactions, deserve further study.Keywords: chronic pancreatitis, pregabalin, placebo, chronic pain treatment, quantitative sensory testing, central sensitization

  12. Molecular Hydrogen Attenuates Neuropathic Pain in Mice

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ndip A

    2012-02-01

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

  14. Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy.

    Science.gov (United States)

    van Haalen, Femke M; van Dijk, Elon H C; Dekkers, Olaf M; Bizino, Maurice B; Dijkman, Greet; Biermasz, Nienke R; Boon, Camiel J F; Pereira, Alberto M

    2018-01-01

    Central serous chorioretinopathy (CSC), a specific form of macular degeneration, has been reported as presenting manifestation of Cushing's syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing's syndrome. It is important to know whether CSC patients should be screened for Cushing's syndrome. Although hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing's syndrome prevalence is increased among chronic CSC (cCSC) patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis. Cross-sectional study. 86 cCSC patients and 24 controls. Prevalence of Cushing's syndrome, HPA axis activity. None of the cCSC patients met the clinical or biochemical criteria of Cushing's syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires. No case of Cushing's syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing's syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

  15. Central blood circulation in children at chronic combined low dose radiation and chemical action

    International Nuclear Information System (INIS)

    Arinchin, A.N.

    2000-01-01

    The state of central blood circulation and its hormonal regulation were studied in 1465 children living permanently under chronic low dose radiation and chemical action. Basic group consisted of 1093 children (579 boys and 514 girls) . 372 children (115 boys and 227 girls permanently living on 'clean' areas) were investigated in control group. Average age was 10,8 years old in basic group and 10,4 years old in the control group. Such parameters as arterial pressure, level of lead in blood and urine, adrenaline, noradrenaline and dophamine content in urine, thyroxine, iodothyronine, prostaglandins and cyclic AMP content in the blood serum has been controlled. Hypotensive states were determined to prevail in children living permanently under chronic low dose radiation and chemical action. The main pathogenic mechanism of this defeat is consider to be a reduction of the sympathoadrenal system activity combined with a decreasing of the thyroid system activity and of cyclic AMP level as well as predominance of prostaglandin depressive activity

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

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    Boris eAlbuquerque

    2013-11-01

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

  18. Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain

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    Ferrari F

    2011-04-01

    Full Text Available Flora Ferrari1, Simonetta Fiorentino1, Laura Mennuni1, Paolo Garofalo1, Ornella Letari1, Stefano Mandelli2, Antonio Giordani3, Marco Lanza1, Gianfranco Caselli11Department of Pharmacology and Toxicology; 2Department of Medicinal Chemistry; 3R&D Chemistry Drug Development and OS, Rottapharm S.p.A., Monza (MB, ItalyAbstract: Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R. However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1ylquinazoline; [CR4056] that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE tissue levels both in the rat cerebral cortex (63.1% ± 4.2%; P<0.05 and lumbar spinal cord (51.3% ± 6.7%; P < 0.05. In the complete Freund's adjuvant (CFA rat model of inflammatory pain, CR4056 was found to be orally active (ED50 = 5.8 mg/kg, by mouth [p.o.]. In the acute capsaicin model, CR4056 completely blocked mechanical hyperalgesia in the injured hind paw (ED50 = 4.1 mg/kg, p.o.; ED100 = 17.9 mg/kg, p.o.. This effect was dose-dependently antagonized by the non-selective imidazoline I2/α2 antagonist idazoxan. In rat models of neuropathic pain, oral administration of CR4056 significantly attenuated mechanical hyperalgesia and allodynia. In summary, the present study suggests a novel

  19. 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

  20. Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

    Science.gov (United States)

    Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

    2017-08-01

    The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

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

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    DosSantos Marcos

    2012-09-01

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

  2. Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats

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    Wei Wang

    2017-05-01

    Full Text Available Neuromuscular compensation of the genioglossus muscle can be induced by chronic intermittent hypoxia (CIH in obstructive sleep apnea to maintain upper airway stability. Noradrenergic activation of hypoglossal nucleus plays a critical role in the central control of the genioglossus. However, it remains unknown whether norepinephrine takes part in the central regulation of the genioglossus during CIH. Adult male Wistar rats (n = 32 were studied to explore the influence of noradrenergic activation of hypoglossal nucleus on the central control of the genioglossus at different stages of CIH. The rats were divided into four groups: normal control or normoxic (NO group, CIH group, CIH + normal saline (NS group, and CIH + prazosin (PZ, α1-adrenergic antagonist group. PZ (0.2 mM, 60 nl and NS (0.9%, 60 nl were microinjected into the hypoglossal nucleus. The responses of the genioglossus corticomotor area to transcranial magnetic stimulation (TMS were recorded on the 1st, 7th, 14th, and 21st day of CIH. The CIH group showed significantly shorter TMS latencies on days 1, 7, and 14 (3.85 ± 0.37 vs. 4.58 ± 0.42, 3.93 ± 0.17 vs. 4.49 ± 0.55, 3.79 ± 0.38 vs. 4.39 ± 0.30 ms, P < 0.05, and higher TMS amplitudes on day 1 (2.74 ± 0.87 vs. 1.60 ± 0.52 mV, P < 0.05 of CIH than the NO group. Compared to the CIH + NS group, the CIH + PZ group showed decreased TMS responses (longer latencies and lower amplitudes only on the 14th day of CIH (3.99 ± 0.28 vs. 4.61 ± 0.48 ms, 2.51 ± 0.67 vs. 1.18 ± 0.62 mV, P < 0.05. These results indicated that noradrenergic activation of the hypoglossal nucleus played a role in the central compensation of genioglossus through α1-adrenoceptor on the 14th day of CIH.

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

    OpenAIRE

    Truini, Andrea

    2017-01-01

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

  4. Cushing’s Syndrome and Hypothalamic–Pituitary–Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy

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    Femke M. van Haalen

    2018-02-01

    Full Text Available ObjectiveCentral serous chorioretinopathy (CSC, a specific form of macular degeneration, has been reported as presenting manifestation of Cushing’s syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing’s syndrome. It is important to know whether CSC patients should be screened for Cushing’s syndrome. Although hypothalamic-pituitary-adrenal (HPA axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing’s syndrome prevalence is increased among chronic CSC (cCSC patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis.DesignCross-sectional study.Patients86 cCSC patients and 24 controls.MeasurementsPrevalence of Cushing’s syndrome, HPA axis activity.ResultsNone of the cCSC patients met the clinical or biochemical criteria of Cushing’s syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires.ConclusionNo case of Cushing’s syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing’s syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

  5. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

    Science.gov (United States)

    Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

    2010-12-01

    Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

  6. [Efficacy of tramadol/acetaminophen medication for central post-stroke pain].

    Science.gov (United States)

    Tanei, Takafumi; Kajita, Yasukazu; Noda, Hiroshi; Takebayashi, Shigenori; Hirano, Masaki; Nakahara, Norimoto; Wakabayashi, Toshihiko

    2013-08-01

    Central post-stroke pain(CPSP)is the most difficult type of central neuropathic pain to control with medical treatment. Opioids are commonly used for chronic neuropathic pain, but their efficacy in treating central neuropathic pain, particularly CPSP, is not clear. Tramadol is an opioid analgesic that, in combination with acetaminophen, has been approved since 2011 for the treatment of non-cancer pain in Japan. In this study we evaluated the efficacy of tramadol/acetaminophen medication for CPSP. We retrospectively reviewed nine cases of CPSP that received oral tramadol/acetaminophen medication. All cases received tramadol/acetaminophen medication after first taking pregabalin then antidepressant medication. Pain levels were assessed before tramadol/acetaminophen medication began and one month after a maintenance dose was reached, using a visual analogue scale(VAS)and the McGill pain questionnaire(MPQ). The mean dose of tramadol was 121±61.6 mg/day. Tramadol/acetaminophen medication was effective in reducing pain in seven of nine cases(77.8%). The VAS improved 32.9±13.8% from pre-to post-medication, and the MPQ improved from 15.4±9.1 pre-medication to 8.1±4.7 post-medication(ppain levels in patients with CPSP, and is a medication option for the treatment of CPSP.

  7. 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.

  8. Observation on the efficacy of Conbercept for chronic central serous chorioretinopathy

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    Liang Yao

    2017-06-01

    Full Text Available AIM:To observe the efficacy of intravitreal conbercept injection for chronic central serous chorioretinopathy(CSC. METHODS: Nine eyes of 9 patients diagnosed as chronic CSC between October 2015 to May 2016 were treated with an intravitreal injection of conbercept(0.5mg/0.05mL(six patients were given the same does of intravitreal injection again at 1mo after the first injection. Follow-up observation was at 1, 2, and 6mo after injection. Observed indicators included best-corrected visual acuity(BCVA, intraocular pressure, optical coherence tomography(OCT, fundus fluorescein angiography(FFA, choroidal indocyanine green angiography(ICGA, macular fovea thickness(CMT, subfoveal choroidal thickness(SFCT. RESULTS:Seven of the 9 patients responded significantly to the drug, while 2 patients had no response. The CMT was 373.12±72.43μm at baseline, which decreased significantly to 332.05±67.13μm, 282.24±62.30μm and 225.56±71.08μm at 1, 2 and 6mo after the intravitreal injection. The mean thickness of SFCT was 422.11±64.82μm before treatment. The choroidal thickness of non-responsive patients before treatment was below average, respectively 353μm and 365μm. The SFCT of 1, 2, and 6mo after treatment was 391.45±75.24μm, 365.53±63.07μm, 355.40±66.65μm. Before treatment and 1mo after, there was no significant difference(P=0.074, but there was statistically significant(PP>0.05.CONCLUSION: Intravitreal conbercept injection in chronic CSC may have some effect in accelerating subertinal fluid resolution and decreasing the CMT. The SFCT within 6mo after treatment was significantly lower than pretreatment. The SFCT may be an indicator of whether patients respond.

  9. The role of the immune system in the generation of neuropathic pain.

    Science.gov (United States)

    Calvo, Margarita; Dawes, John M; Bennett, David L H

    2012-07-01

    Persistent pain is a sequela of several neurological conditions with a primary immune basis, such as Guillain-Barré syndrome and multiple sclerosis. Additionally, diverse forms of injury to the peripheral or the central nervous systems--whether traumatic, metabolic, or toxic--result in substantial recruitment and activation of immune cells. This response involves the innate immune system, but evidence also exists of T-lymphocyte recruitment, and in some patient cohorts antibodies to neuronal antigens have been reported. Mediators released by immune cells, such as cytokines, sensitise nociceptive signalling in the peripheral and central nervous systems. Preclinical data suggest an immune pathogenesis of neuropathic pain, but clinical evidence of a central role of the immune system is less clear. An important challenge for the future is to establish to what extent this immune response initiates or maintains neuropathic pain in patients and thus whether it is amenable to therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. [Optimization of registry of deaths from chronic kidney disease in agricultural communities in Central America].

    Science.gov (United States)

    Escamilla-Cejudo, José Antonio; Báez, Jorge Lara; Peña, Rodolfo; Luna, Patricia Lorena Ruiz; Ordunez, Pedro

    2016-11-01

    Several Central American countries are seeing continued growth in the number of deaths from chronic kidney disease of nontraditional causes (CKDnT) among farm workers and there is underreporting. This report presents the results of a consensus process coordinated by the Pan American Health Organization/World Health Organization (PAHO/WHO), the United States Centers for Disease Control and Prevention (CDC), and the Latin American Society of Nephrology and Hypertension (SLANH). This consensus seeks to increase the probability of detecting and recording deaths from these causes. There has been recognition of the negative impact of the lack of a standardized instrument and the lack of training in the medical profession for adequate registration of the cause or causes of death. As a result of the consensus, the following has been proposed: temporarily use a code from the Codes for Special Purposes in the International Classification of Diseases (ICD-10); continue to promote use of the WHO international standardized instrument for recording causes and preceding events related to death; increase training of physicians responsible for filling out death certificates; take action to increase the coverage and quality of information on mortality; and create a decision tree to facilitate selection of CKDnT as a specific cause of death, while presenting the role that different regional and subregional mechanisms in the Region of the Americas should play in order to improve CKD and CKDnT mortality records.

  11. Mitochondria Play a Central Role in Nonischemic Cardiomyocyte Necrosis: Common to Acute and Chronic Stressor States

    Science.gov (United States)

    Khan, M. Usman; Cheema, Yaser; Shahbaz, Atta U.; Ahokas, Robert A.; Sun, Yao; Gerling, Ivan C.; Bhattacharya, Syamal K.; Weber, Karl T.

    2012-01-01

    The survival of cardiomyocytes must be ensured as the myocardium adjusts to a myriad of competing physiologic and pathophysiologic demands. A significant loss of these contractile cells, together with their replacement by stiff fibrillar collagen in the form of fibrous tissue accounts for a transition from a usually efficient muscular pump into one that is failing. Cellular and subcellular mechanisms involved in the pathogenic origins of cardiomyocyte cell death have long been of interest. This includes programmed molecular pathways to either necrosis or apoptosis which are initiated from ischemic or nonischemic origins. Herein we focus on the central role played by a mitochondriocentric signal-transducer-effector pathway to nonischemic cardiomyocyte necrosis which is common to acute and chronic stressor states. We begin by building upon the hypothesis advanced by Albrecht Fleckenstein and coworkers some 40 years ago based on the importance of calcitropic hormone- mediated intracellular Ca2+ overloading which predominantly involves subsarcolemmal mitochondria and is the signal to pathway activation. Other pathway components, which came to be recognized in subsequent years, include the induction of oxidative stress and opening of the mitochondrial inner membrane permeability transition pore. The ensuing loss of cardiomyocytes and consequent replacement fibrosis, or scarring, represents a disease of adaptation and a classic example of when homeostasis begets dyshomeostasis. PMID:22328074

  12. Iron deposits in the chronically inflamed central nervous system and contributes to neurodegeneration.

    Science.gov (United States)

    Andersen, Hjalte Holm; Johnsen, Kasper Bendix; Moos, Torben

    2014-05-01

    Neurodegenerative disorders are characterized by the presence of inflammation in areas with neuronal cell death and a regional increase in iron that exceeds what occurs during normal aging. The inflammatory process accompanying the neuronal degeneration involves glial cells of the central nervous system (CNS) and monocytes of the circulation that migrate into the CNS while transforming into phagocytic macrophages. This review outlines the possible mechanisms responsible for deposition of iron in neurodegenerative disorders with a main emphasis on how iron-containing monocytes may migrate into the CNS, transform into macrophages, and die out subsequently to their phagocytosis of damaged and dying neuronal cells. The dying macrophages may in turn release their iron, which enters the pool of labile iron to catalytically promote formation of free-radical-mediated stress and oxidative damage to adjacent cells, including neurons. Healthy neurons may also chronically acquire iron from the extracellular space as another principle mechanism for oxidative stress-mediated damage. Pharmacological handling of monocyte migration into the CNS combined with chelators that neutralize the effects of extracellular iron occurring due to the release from dying macrophages as well as intraneuronal chelation may denote good possibilities for reducing the deleterious consequences of iron deposition in the CNS.

  13. A Review of Select Centralized Pain Syndromes

    Directory of Open Access Journals (Sweden)

    David R. Spiegel

    2015-01-01

    Full Text Available Pain can be broadly divided into 3 classes, including nociceptive or inflammatory pain (protective, neuropathic (pathological, occurring after damage to the nervous system, or centralized (pathological, due to abnormal function but with no damage or inflammation to the nervous system. The latter has been posited to occur when descending analgesic pathways are attenuated and/or glutamatergic transmission is facilitated. Additionally, this “pain prone phenotype” can be associated with early life trauma and a suboptimal response to opiates. This article will review the relationships between centralized pain syndromes (ie, fibromyalgia, chronic low back pain, childhood sexual abuse, and opiate misuse. Finally, treatment implications, potentially effecting primary care physicians, will be discussed.

  14. Differential transcriptional profiling of damaged and intact adjacent dorsal root ganglia neurons in neuropathic pain.

    Directory of Open Access Journals (Sweden)

    A K Reinhold

    Full Text Available Neuropathic pain, caused by a lesion in the somatosensory system, is a severely impairing mostly chronic disease. While its underlying molecular mechanisms are not thoroughly understood, neuroimmune interactions as well as changes in the pain pathway such as sensitization of nociceptors have been implicated. It has been shown that not only are different cell types involved in generation and maintenance of neuropathic pain, like neurons, immune and glial cells, but, also, intact adjacent neurons are relevant to the process. Here, we describe an experimental approach to discriminate damaged from intact adjacent neurons in the same dorsal root ganglion (DRG using differential fluorescent neuronal labelling and fluorescence-activated cell sorting (FACS. Two fluorescent tracers, Fluoroemerald (FE and 1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI, were used, whose properties allow us to distinguish between damaged and intact neurons. Subsequent sorting permitted transcriptional analysis of both groups. Results and qPCR validation show a strong regulation in damaged neurons versus contralateral controls as well as a moderate regulation in adjacent neurons. Data for damaged neurons reveal an mRNA expression pattern consistent with established upregulated genes like galanin, which supports our approach. Moreover, novel genes were found strongly regulated such as corticotropin-releasing hormone (CRH, providing novel targets for further research. Differential fluorescent neuronal labelling and sorting allows for a clear distinction between primarily damaged neuropathic neurons and "bystanders," thereby facilitating a more detailed understanding of their respective roles in neuropathic processes in the DRG.

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

    Science.gov (United States)

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

    2018-03-15

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

  16. Management of neuropathic pain following treatment for breast cancer in the absence of recurrence: a challenge for the radiation oncologist

    International Nuclear Information System (INIS)

    Clubb, B.

    2004-01-01

    This report reviews various management options for treatment-induced neuropathic pain in breast cancer. First-line options include tricyclic antidepressants and anticonvulsant drugs. Opioids should be prescribed according to published guidelines. Second-line treatments include lignocaine, mexiletine and ketamine. Sympatholytic therapies are available to patients with features of chronic regional pain syndrome. Anti-inflammatory agents are used for neurogenic inflammation. Surgical interventions are considered for refractory neuropathic pain. Interdisciplinary management is appropriate when persisting pain causes physical and psychosocial disabilities. Copyright (2004) Blackwell Science Pty Ltd

  17. MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain

    OpenAIRE

    Wang, Conghui; Jiang, Qi; Wang, Min; Li, Dong

    2015-01-01

    Purpose: we aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. Methods: We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and ace...

  18. Chronic whiplash and central sensitization; an evaluation of the role of a myofascial trigger points in pain modulation

    Directory of Open Access Journals (Sweden)

    Freeman Michael D

    2009-04-01

    Full Text Available Abstract Objective it has been established that chronic neck pain following whiplash is associated with the phenomenon of central sensitization, in which injured and uninjured parts of the body exhibit lowered pain thresholds due to an alteration in central pain processing. it has furthermore been hypothesized that peripheral sources of nociception in the muscles may perpetuate central sensitization in chronic whiplash. the hypothesis explored in the present study was whether myofascial trigger points serve as a modulator of central sensitization in subjects with chronic neck pain. Design controlled case series. Setting outpatient chronic pain clinic. Subjects seventeen patients with chronic and intractable neck pain and 10 healthy controls without complaints of neck pain. Intervention symptomatic subjects received anesthetic infiltration of myofascial trigger points in the upper trapezius muscles and controls received the anesthetic in the thigh. Outcome measures: pre and post injection cervical range of motion, pressure pain thresholds (ppt over the infraspinatus, wrist extensor, and tibialis anterior muscles. sensitivity to light (photophobia and subjects' perception of pain using a visual analog scale (vas were also evaluated before and after injections. only the ppt was evaluated in the asymptomatic controls. Results immediate (within 1 minute alterations in cervical range of motion and pressure pain thresholds were observed following an average of 3.8 injections with 1–2 cc of 1% lidocaine into carefully identified trigger points. cervical range of motion increased by an average of 49% (p = 0.000 in flexion and 44% (p = 0.001 in extension, 47% (p = 0.000 and 28% (p Conclusion the present data suggest that myofascial trigger points serve to perpetuate lowered pain thresholds in uninjured tissues. additionally, it appears that lowered pain thresholds associated with central sensitization can be immediately reversed, even when associated

  19. Ascending central canal dilation and progressive ependymal disruption in a contusion model of rodent chronic spinal cord injury

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    Keirstead Hans S

    2007-09-01

    Full Text Available Abstract Background Chronic spinal cord injury (SCI can lead to an insidious decline in motor and sensory function in individuals even years after the initial injury and is accompanied by a slow and progressive cytoarchitectural destruction. At present, no pathological mechanisms satisfactorily explain the ongoing degeneration. Methods Adult female Sprague-Dawley rats were anesthetized laminectomized at T10 and received spinal cord contusion injuries with a force of 250 kilodynes using an Infinite Horizon Impactor. Animals were randomly distributed into 5 groups and killed 1 (n = 4, 28 (n = 4, 120 (n = 4, 450 (n = 5, or 540 (n = 5 days after injury. Morphometric and immunohistochemical studies were then performed on 1 mm block sections, 6 mm cranial and 6 mm caudal to the lesion epicenter. The SPSS 11.5 t test was used to determine differences between quantitative measures. Results Here, we document the first report of an ascending central canal dilation and progressive ependymal disruption cranial to the epicenter of injury in a contusion model of chronic SCI, which was characterized by extensive dural fibrosis and intraparenchymal cystic cavitation. Expansion of the central canal lumen beyond a critical diameter corresponded with ependymal cell ciliary loss, an empirically predictable thinning of the ependymal region, and a decrease in cell proliferation in the ependymal region. Large, aneurysmal dilations of the central canal were accompanied by disruptions in the ependymal layer, periependymal edema and gliosis, and destruction of the adjacent neuropil. Conclusion Cells of the ependymal region play an important role in CSF homeostasis, cellular signaling and wound repair in the spinal cord. The possible effects of this ascending pathology on ependymal function are discussed. Our studies suggest central canal dilation and ependymal region disruption as steps in the pathogenesis of chronic SCI, identify central canal dilation as a marker of

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

    Science.gov (United States)

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

    2009-10-08

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

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Reaction to topical capsaicin in spinal cord injury patients with and without central pain

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Pedersen, Louise H.; Terkelsen, Astrid J.

    2007-01-01

    of a spinal cord injury which already is hyperexcitable, would cause enhanced responses in patients with central pain at the level of injury compared to patients without neuropathic pain and healthy controls. Touch, punctuate stimuli, cold stimuli and topical capsaicin was applied above, at, and below injury......Central neuropathic pain is a debilitating and frequent complication to spinal cord injury (SCI). Excitatory input from hyperexcitable cells around the injured grey matter zone is suggested to play a role for central neuropathic pain felt below the level of a spinal cord injury. Direct evidence...... at the level of injury. Keywords: Spinal cord injury; Neuropathic pain; Capsaicin; Neuronal hyperexcitability; Hyperalgesia; Blood flow...

  3. Preemptive analgesic effect of lidocaine in a chronic neuropathic pain model Efeito analgésico preemptivo da lidocaína em modelo de dor crônica neuropática

    Directory of Open Access Journals (Sweden)

    Leonardo M. Batista

    2009-12-01

    Full Text Available Preemptive analgesia inhibits the progression of pain caused by surgical lesions. To analyze the effect of lidocaine on postoperative pain relief, we performed compression of the right sciatic nerve in Wistar rats and observed the differences on behavior between the group that received lidocaine and the group that was not treated with the local anesthetics pre-operatively. Group 1 was not operated (control; group 2 underwent the sciatic nerve ligature without lidocaine; group 3, underwent surgery with previous local infiltration of lidocaine. Group 2 showed significantly longer scratching times with a peak on day 14 post-operative (p=0.0005 and reduction in the latency to both noxious (p=0.003 and non-noxious (p=0.004 thermal stimulus. Group 3 presented significantly shorter scratching times (p=0.004 and longer latency times when compared to Group 2. Preemptive use of lidocaine 2% can potentially reduce the postoperative neuropathic pain associated with sciatic nerve compression.A analgesia preemptiva inibe a progressão da dor causada por lesão cirúrgica. Para analisar o efeito da lidocaína na diminuição da dor pós-operatória, submetemos ratos Wistar a compressão cirúrgica do nervo ciático e observamos diferenças em alguns padrões de comportamento entre o grupo tratado com lidocaína pré-operatória e o grupo não-tratado com o anestésico local. O grupo 1 não foi operado (controle; o grupo 2, submetido a ligadura do nervo ciático sem lidocaína, apresentou significativo aumento do tempo de coçar-se com um pico no 14º pós-operatório (p=0.0005 e redução na latência para os estímulos térmicos nocivo (p=0.003 e não-nocivo (p=0.004; o grupo 3, operado com a droga preemptiva, demonstrou significativo decréscimo no tempo de coçar-se (p=0.004 e maiores tempos de latência quando comparados aos do grupo 2. O uso preemptivo da lidocaína 2% pode, potencialmente, reduzir a dor neuropática pós-operatória associada à compress

  4. Possible analgesic effect of vigabatrin in animal experimental chronic neuropathic pain Possível efeito analgésico da vigabatrina na dor neuropática crônica experimental animal

    Directory of Open Access Journals (Sweden)

    NILZA D. ALVES

    1999-12-01

    Full Text Available Since anticonvulsants have been used for treating neuralgias, an interest has arisen to experimentally test vigabatrin for its gabaergic mechanism of action. For this, 41 Wistar rats were used, and in 25 of them a constrictive sciatic neuropathy was induced (Bennet & Xie model. For testing pain symptoms, spontaneous (scratching and evoked behaviors to noxious (46o C and non-noxious (40o C thermal stimuli were quantified. Moreover, a comparative pharmacological study of vigabatrin with other analgesic anticonvulsant drugs was also performed. The results showed a possible dose-dependent analgesic effect of vigabatrin (gamma-vinyl-GABA on experimental neuropathic pain, as shown by the significant (pO uso de anticonvulsivantes no tratamento de neuralgias despertou um interesse em testar novas drogas anticonvulsivantes, e dentre essas a vigabatrina por possuir mecanismo de ação gabaérgico. Para isso, foram usados 41 ratos Wistar e em 25 deles induziu-se neuropatia ciática constritiva (modelo de Bennett & Xie. Para testar sintomas de dor, foram quantificados comportamentos espontâneos (coçar-se e evocados, por meio de estímulos térmicos nocivos (46oC e não-nocivos (40oC. Além disso, realizou-se estudo comparativo da vigabatrina com outros anticonvulsivantes analgésicos. Os resultados mostraram um possível efeito analgésico, dose-dependente, de vigabatrina (gama-vinil-GABA em dor neuropática experimental. Isso foi evidenciado pela diminuição significativa (p<0,05 do comportamento de coçar-se e pelo aumento significativo (p<0,05 da latência de retirada da pata posterior direita a estímulos térmicos nocivos. Isso foi corroborado por achados semelhantes em experimentos com anticonvulsivantes (carbamazepina, fenitoína e ácido valpróico analgésicos. Esse possível efeito analgésico da vigabatrina (ainda não descrito na literatura não é mediado pelo sistema opióide.

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

    Science.gov (United States)

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

    2013-01-01

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

  6. 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.

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

    Science.gov (United States)

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

    2014-06-01

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

  8. Bilateral Changes of Spontaneous Activity Within the Central Auditory Pathway Upon Chronic Unilateral Intracochlear Electrical Stimulation.

    Science.gov (United States)

    Basta, Dietmar; Götze, Romy; Gröschel, Moritz; Jansen, Sebastian; Janke, Oliver; Tzschentke, Barbara; Boyle, Patrick; Ernst, Arne

    2015-12-01

    In recent years, cochlear implants have been applied successfully for the treatment of unilateral hearing loss with quite surprising benefit. One reason for this successful treatment, including the relief from tinnitus, could be the normalization of spontaneous activity in the central auditory pathway because of the electrical stimulation. The present study, therefore, investigated at a cellular level, the effect of a unilateral chronic intracochlear stimulation on key structures of the central auditory pathway. Normal-hearing guinea pigs were mechanically single-sided deafened through a standard HiFocus1j electrode array (on a HiRes 90k cochlear implant) being inserted into the first turn of the cochlea. Four to five electrode contacts could be used for the stimulation. Six weeks after surgery, the speech processor (Auria) was fitted, based on tNRI values and mounted on the animal's back. The two experimental groups were stimulated 16 hours per day for 90 days, using a HiRes strategy based on different stimulation rates (low rate (275 pps/ch), high rate (5000 pps/ch)). The results were compared with those of unilateral deafened controls (implanted but not stimulated), as well as between the treatment groups. All animals experienced a standardized free field auditory environment. The low-rate group showed a significantly lower average spontaneous activity bilaterally in the dorsal cochlear nucleus and the medial geniculate body than the controls. However, there was no difference in the inferior colliculus and the primary auditory cortex. Spontaneous activity of the high-rate group was also reduced bilaterally in the dorsal cochlear nucleus and in the primary auditory cortex. No differences could be observed between the high-rate group and the controls in the contra-lateral inferior colliculus and medial geniculate body. The high-rate group showed bilaterally a higher activity in the CN and the MGB compared with the low-rate group, whereas in the IC and in the

  9. Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso, central Brazil

    Directory of Open Access Journals (Sweden)

    Francisco Kennedy Scofoni Faleiros de Azevedo

    2012-03-01

    Full Text Available In Brazil, the treatment of hepatitis C virus (HCV infection is funded by the national public health system (SUS. To evaluate treatment results in the state of Mato Grosso, central Brazil, we have consulted the files of the office of the State Department of Health responsible for supplying such medications. We obtained information on 232 treatments of 201 patients who underwent treatment in or prior to 2008. The study was conducted by reviewing medical records, making telephone calls and interviewing the assistant physicians. Thirty-nine patients (19.4% had cirrhosis and HCV genotype 1 predominated (64.3%. Excluding patients with comorbidities or treatment without ribavirin we analysed 175 treatments (sustained virologic response occurred in 32.6% of cases. Twenty-six of these 175 were retreatments and the sustained virological response (SVR rate among them was 30.8%; the SVR rate was 32.9% among those receiving treatment for the first time. The SVR rate of genotype 1 patients was 27.8%, whereas it was 37.5% in non-1 genotype patients. The adjusted multivariate analysis showed association of SVR with the absence of cirrhosis [odds ratio (OR: 7.7; confidence interval (CI 95%: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95%: 1.5, 21.4, non-1 genotype (OR: 5.3; CI 95%: 1.7, 16.7 and uninterrupted treatment (OR: 9.0; CI 95%: 3.3, 45.4. The SVR rates were similar to those found in other Brazilian studies about HCV, but lower than those found in national and international clinical trials. These data suggest that the treatments of chronic hepatitis C that are made available by SUS does not, under normal conditions, work as well as the original controlled studies indicated.

  10. Effects of combined aerobic and resistance exercise on central arterial stiffness and gait velocity in patients with chronic poststroke hemiparesis.

    Science.gov (United States)

    Lee, Yong Hee; Park, Soo Hyun; Yoon, Eun Sun; Lee, Chong-Do; Wee, Sang Ouk; Fernhall, Bo; Jae, Sae Young

    2015-09-01

    The effects of combined aerobic and resistance exercise training on central arterial stiffness and gait velocity in patients with chronic poststroke hemiparesis were investigated. Twenty-six patients with chronic poststroke hemiparesis were randomly assigned to either the combined aerobic and resistance exercise group (n = 14) or the control group (n = 12). The exercise intervention group received a combined aerobic and resistance exercise training (1 hr/day, three times/week for 16 wks), whereas the control group received usual care. Central arterial stiffness was determined by pulse wave velocity and augmentation index. Gait velocity was assessed using the 6-min walk test, 10-m walk test, and the Timed Up-and-Go test. Patients in the exercise intervention group had greater improvement of mean pulse wave velocity (P hemiparesis.

  11. Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

    Science.gov (United States)

    Wen, Hui-Zhong; Gao, Shi-Hao; Zhao, Yan-Dong; He, Wen-Juan; Tian, Xue-Long; Ruan, Huai-Zhen

    2017-01-01

    Background: Transcranial direct current stimulation (tDCS) is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters. Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1) on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia. Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI), we measured pain thresholds before and after anodal-tDCS (A-tDCS) using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models). Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS) and contralateral-tDCS (con-tDCS) produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats. Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical applications. PMID

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

    Science.gov (United States)

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

    2016-03-01

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

  13. Effects of Stress and Relaxation on Central Pain Modulation in Chronic Whiplash and Fibromyalgia Patients Compared to Healthy Controls.

    Science.gov (United States)

    Coppieters, Iris; Cagnie, Barbara; Nijs, Jo; van Oosterwijck, Jessica; Danneels, Lieven; De Pauw, Robby; Meeus, Mira

    2016-03-01

    Compelling evidence has demonstrated that impaired central pain modulation contributes to persistent pain in patients with chronic whiplash associated disorders (WAD) and fibromyalgia (FM). However, there is limited research concerning the influence of stress and relaxation on central pain modulation in patients with chronic WAD and FM. The present study aims to investigate the effects of acute cognitive stress and relaxation on central pain modulation in chronic WAD and FM patients compared to healthy individuals. A randomized crossover design was employed. The present study took place at the University of Brussels, the University Hospital Brussels, and the University of Antwerp. Fifty-nine participants (16 chronic WAD patients, 21 FM, 22 pain-free controls) were enrolled and subjected to various pain measurements. Temporal summation (TS) of pain and conditioned pain modulation (CPM) were evaluated. Subsequently, participants were randomly allocated to either a group that received progressive relaxation therapy or a group that performed a battery of cognitive tests (= cognitive stressor). Afterwards, all pain measurements were repeated. One week later participant groups were switched. A significant difference was found between the groups in the change in TS in response to relaxation (P = 0.008) and cognitive stress (P = 0.003). TS decreased in response to relaxation and cognitive stress in chronic WAD patients and controls. In contrast, TS increased after both interventions in FM patients. CPM efficacy decreased in all 3 groups in response to relaxation (P = 0.002) and cognitive stress (P = 0.001). The obtained results only apply for a single session of muscle relaxation therapy and cognitive stress, whereby no conclusions can be made for effects on pain perception and modulation of chronic cognitive stress and long-term relaxation therapies. A single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with

  14. Chronic kidney disease of nontraditional etiology in Central America: a provisional epidemiologic case definition for surveillance and epidemiologic studies.

    Science.gov (United States)

    Lozier, Matthew; Turcios-Ruiz, Reina Maria; Noonan, Gary; Ordunez, Pedro

    2016-11-01

    SYNOPSIS Over the last two decades, experts have reported a rising number of deaths caused by chronic kidney disease (CKD) along the Pacific coast of Central America, from southern Mexico to Costa Rica. However, this specific disease is not associated with traditional causes of CKD, such as aging, diabetes, or hypertension. Rather, this disease is a chronic interstitial nephritis termed chronic kidney disease of nontraditional etiology (CKDnT). According to the Pan American Health Organization (PAHO) mortality database, there are elevated rates of deaths related to kidney disease in many of these countries, with the highest rates being reported in El Salvador and Nicaragua. This condition has been identified in certain agricultural communities, predominantly among male farmworkers. Since CKD surveillance systems in Central America are under development or nonexistent, experts and governmental bodies have recommended creating standardized case definitions for surveillance purposes to monitor and characterize this epidemiological situation. A group of experts from Central American ministries of health, the U.S. Centers for Disease Control and Prevention (CDC), and PAHO held a workshop in Guatemala to discuss CKDnT epidemiologic case definitions. In this paper, we propose that CKD in general be identified by the standard definition internationally accepted and that a suspect case of CKDnT be defined as a person age CKDnT is defined as a suspect case with the same findings confirmed three or more months later.

  15. 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...

  16. Central neuropeptide Y plays an important role in mediating the adaptation mechanism against chronic stress in male rats.

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    Yang, Yu; Babygirija, Reji; Zheng, Jun; Shi, Bei; Sun, Weinan; Zheng, Xiaojiao; Zhang, Fan; Cao, Yu

    2018-02-07

    Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF), and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days, 1-5, of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, while central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism, and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, over-expressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress. Copyright © 2018 Endocrine Society.

  17. Study of Low-grade Chronic Inflammatory Markers in Men with Central Obesity: Cathepsin S was Correlated with Waist Circumference

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    Adriana Todingrante

    2013-08-01

    Full Text Available BACKGROUND: There is a prevalence increase of overweight and obesity in Indonesia. Central obesity can lead a variety of chronic diseases through the inflammatory process. There are some markers for low-grade chronic inflammatory, such as cathepsin S, high sensitivity C-reactive protein (hs-CRP, interleukin-1- beta (IL-1β. To our current interest that central obesity can lead to various chronic diseases through the inflammatory process, we conducted a study to investigate correlation of Cathepsin S, hs-CRP, IL-1β in men with central obesity. METHODS: A cross-sectional study was conducted. Seventy-eight selected subjects were examined to collect anthropometric data and prepared for sample collection. Collected samples were processed for the following biochemical analyses: fasting glucose, high density lipoprotein (HDL-cholesterol, triglyceride, serum glutamic oxaloacetic transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, cathepsin S, hs-CRP, and IL-1β. Data distribution and variable correlation were then statistically analyzed. RESULTS: There were significant correlations between waist circumference (WC and cathepsin S (p=0.030; r=0.214, hs-CRP and cathepsin S (p=0.007; r=0.276, triglyceride and IL-1β (p=0.019; r=-0.235, WC and systolic blood pressure (SBP (p=0.003; r=-0.312, WC and fasting glucose (p=0.000; r=0.380, WC and body mass index (BMI (p=0.000; r=0.708. CONCLUSIONS: Our study showed that cathepsin S was correlated with central obesity, suggesting that cathepsin S could be a potential inflammatory marker in central obesity in the future. KEYWORDS: obesity, inflammation, hs-CRP, cathepsin S, IL-1β, waist circumference.

  18. CENTRAL SENSITIZATION AND MEDICATION IN SPINAL CORD INJURED IN-PATIENTS. A CROSS-SECTIONAL CLINICAL STUDY

    DEFF Research Database (Denmark)

    Rosendahl, A; Kasch, Helge

    Background and aims: A major proportion of spinal cord injured subjects (SCIS) suffers from chronic pain. A majority with neuropathic pain, being: shooting, burning and stabbing. Neurological examination reveals signs of central sensitization (CS) e.g. allodynia and hyperalgesia. CS plays...... an important role in maintained neuropathic pain conditions and may lead to or be induced by analgesics. Medication-overuse-headaches (MOH) alter CNS pain processing systems, and the situation is reversed after discontinuation of headache medication. Aim: To determine the occurrence of CS and conditions...... pressure algometry, Von Frey filaments and pinprick test. Patients fulfill McGill Pain Questionnaire and the International SCI pain data-set. All participants undergo examination of the Pressure Pain Detection Threshold, Pressure Pain Tolerance Threshold, Mechanical Detection Threshold, and Wind...

  19. Chronic Cardiovascular Disease Mortality in Mountaintop Mining Areas of Central Appalachian States

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    Esch, Laura; Hendryx, Michael

    2011-01-01

    Purpose: To determine if chronic cardiovascular disease (CVD) mortality rates are higher among residents of mountaintop mining (MTM) areas compared to mining and nonmining areas, and to examine the association between greater levels of MTM surface mining and CVD mortality. Methods: Age-adjusted chronic CVD mortality rates from 1999 to 2006 for…

  20. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    NARCIS (Netherlands)

    Bouwense, S.A.; Olesen, S.S.; Drewes, A.M.; Goor, H. van; Wilder-Smith, O.H.G.

    2015-01-01

    BACKGROUND: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs

  1. Functional brain imaging: what has it brought to our understanding of neuropathic pain? A special focus on allodynic pain mechanisms.

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    Peyron, Roland

    2016-02-01

    Brain responses to nociception are well identified. The same is not true for allodynic pain, a strong painful sensation in response to touch or innocuous cold stimuli that may be experienced by patients with neuropathic pain. Brain (or spinal cord) reorganization that may explain this paradoxical perception still remains largely unknown. Allodynic pain is associated with abnormally increased activity in SII and in the anterior insular cortex, contralateral and/or ipsilateral to allodynia. Because a bilateral increase in activity has been repeatedly reported in these areas in nociceptive conditions, the observed activation during allodynia can explain that a physiologically nonpainful stimulus could be perceived by the damaged nervous system as a painful one. Both secondary somatosensory and insular cortices receive input from the thalamus, which is a major relay of sensory and spinothalamic pathways, the involvement of which is known to be crucial for the development of neuropathic pain. Both thalamic function and structure have been reported to be abnormal or impaired in neuropathic pain conditions including in the basal state, possibly explaining the spontaneous component of neuropathic pain. A further indication as to how the brain can create neuropathic pain response in SII and insular cortices stems from examples of diseases, including single-case reports in whom a focal brain lesion leads to central pain disappearance. Additional studies are required to certify the contribution of these areas to the disease processes, to disentangle abnormalities respectively related to pain and to deafferentation, and, in the future, to guide targeting of stimulation studies.

  2. Low doses of dextromethorphan have a beneficial effect in the treatment of neuropathic pain.

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    Morel, Véronique; Pickering, Gisèle; Etienne, Monique; Dupuis, Amandine; Privat, Anne-Marie; Chalus, Maryse; Eschalier, Alain; Daulhac, Laurence

    2014-12-01

    N-methyl-D-aspartate receptor (NMDAR) antagonists may be given in persistent neuropathic pain, but adverse events especially with ketamine may limit their clinical use. Less central and cognitive adverse events are described with dextromethorphan and memantine. These molecules have been explored in many preclinical and clinical studies, but data are conflicting as regards neuropathic pain alleviation. Dextromethorphan and memantine have been administered to animals after spinal nerve ligation (SNL) to evaluate their antinociceptive/cognitive effects and associated molecular events, including the phosphorylation of several tyrosine (pTyr(1336), pTyr(1472)) residues in the NR2B NMDAR subunit. Spinal nerve ligation and sham animals received dextromethorphan (10 mg/kg, i.p.), memantine (20 mg/kg, i.p.) or saline (1 mL/kg, i.p.). These drugs were administered once symptoms of allodynia and hyperalgesia had developed. Tests were carried out before and after surgery. Tactile allodynia, mechanical hyperalgesia and spatial memory were, respectively, evaluated by von Frey, Randall & Selitto and Y-maze tests and molecular events by Western blot analysis. Spinal nerve-ligated animals displayed nociception and impaired spatial memory. Dextromethorphan, but not memantine, reversed neuropathic pain (NP) symptoms, restored spatial memory integrity and decreased the expression of pTyr(1336)NR2B. Following postoperative administration of dextromethorphan, this study has demonstrated for the first time a concordance between behaviour, cognitive function and molecular events via pTyr(1336)NR2B for neuropathic pain alleviation. Confirmation of these findings in patients would constitute a major step forward in the treatment of neuropathic pain and in the improvement of cognitive function and quality of life. © 2014 Société Française de Pharmacologie et de Thérapeutique.

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

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

    2017-01-01

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

  4. Identification of key genes and pathways associated with neuropathic pain in uninjured dorsal root ganglion by using bioinformatic analysis

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    Chen CJ

    2017-11-01

    Full Text Available Chao-Jin Chen,* De-Zhao Liu,* Wei-Feng Yao, Yu Gu, Fei Huang, Zi-Qing Hei, Xiang Li Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Purpose: Neuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL by using bioinformatic analysis.Materials and methods: The microarray profile GSE24982 was downloaded from the Gene Expression Omnibus database to identify DEGs between DRGs in SNL and sham rats. The prioritization for these DEGs was performed using the Toppgene database followed by gene ontology and pathway enrichment analyses. The relationships among DEGs from the protein interactive perspective were analyzed using protein–protein interaction (PPI network and module analysis. Real-time polymerase chain reaction (PCR and Western blotting were used to confirm the expression of DEGs in the rodent neuropathic pain model.Results: A total of 206 DEGs that might play a role in neuropathic pain were identified in L4 DRG, of which 75 were upregulated and 131 were downregulated. The upregulated DEGs were enriched in biological processes related to transcription regulation and molecular functions such as DNA binding, cell cycle, and the FoxO signaling pathway. Ctnnb1 protein had the highest connectivity degrees in the PPI network. The in vivo studies also validated that mRNA and protein levels of Ctnnb1 were

  5. What Are the Predictors of Altered Central Pain Modulation in Chronic Musculoskeletal Pain Populations? A Systematic Review.

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    Clark, Jacqui; Nijs, Jo; Yeowell, Gillian; Goodwin, Peter Charles

    2017-09-01

    Altered central pain modulation is the predominant pain mechanism in a proportion of chronic musculoskeletal pain disorders and is associated with poor outcomes. Although existing studies predict poor outcomes such as persistent pain and disability, to date there is little consensus on what factors specifically predict altered central pain modulation. To review the existing literature on the predictive factors specifically for altered central pain modulation in musculoskeletal pain populations. This is a systematic review in accordance with supplemented PRISMA guidelines. A systematic search was performed by 2 mutually blinded reviewers. Relevant articles were screened by title and abstract from Medline, Embase, PubMed, CINAHL, and Web of Science electronic databases. Alternative sources were also sought to locate missed potential articles. Eligibility included studies published in English, adults aged 18 to 65, musculoskeletal pain, baseline measurements taken at the pre-morbid or acute stage, > 3-month follow-up time after pain onset, and primary outcome measures specific to altered central pain modulation. Studies were excluded where there were concurrent diseases or they were non-predictive studies. Risk of bias was assessed using the quality in prognostic studies (QUIPS) tool. Study design, demographics, musculoskeletal region, inclusion/exclusion criteria, measurement timelines, predictor and primary outcome measures, and results were extracted. Data were synthesized qualitatively and strength of evidence was scored using the grading of recommendations, assessment, development, and evaluations (GRADE) scoring system. Nine eligible articles were located, in various musculoskeletal populations (whiplash, n = 2; widespread pain, n = 5; temporomandibular disorder, n = 2). Moderate evidence was found for 2 predictive factors of altered central pain modulation: 1) high sensory sensitivity (using genetic testing or quantitative sensory tests), and 2) psychological

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

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

    2011-11-01

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

  7. Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

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    Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

    2016-01-01

    One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

  8. Duloxetine in the management of diabetic peripheral neuropathic pain

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    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

  9. Processos inflamatorios cronicos do sistema nervoso central: aspectos neurocirurgicos Inflamatory chronic processes of the central nervous system: neurosurgical aspects

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    Nubor Orlando Facure

    1976-03-01

    Full Text Available São relatados 35 casos de pacientes com síndrome de hipertensão intra-craniana causada por processos inflamatórios crônicos do sistema nervoso central. Apesar da multiplicidade dos agentes etiológicos, a conduta neuro-cirúrgica para a solução da hipertensão intracraniana é semelhante nestes processos. Os pacientes foram divididos em dois grupos. O grupo 1 inclui 7 pacientes nos quais o quadro clínico e neuro-radiológico era de lesão expansiva intracerebral. Estes pacientes foram submetidos a cranotomia com exerese do processo expansivo: tratava-se de cisticercos múltiplos em 5 casos, tuberculoma em um e granuloma blastomicótico em outro. A mortalidade foi nula e não houve recidiva da hipertensão intracraniana. Nos pacientes do grupo 2 as lesões fundamentais são representadas pela ependimite granulosa e leptomeningite crônica das cisternas basais. Os quadros clínico e neuro-radiológico são de hidrocefalia com dilatação ventricular e frequentemente sem sintais neurológicos focais. O prognóstico nestes casos é mais grave devido quase sempre à progressão da doença. Nos 28 pacientes incluídos neste grupo o tratamento de escolha foi a derivação ventriculoatrial ou ventrículoperitonial. A mortalidade foi de 39,2%.A study into the neurosurgical approach to thirty-five patients with increased intracranial pressure due to inflamatory diseases affecting the central nervous system and meninges is reported. The entities under consideration were found to have similar surgical aspects despite the heterogeneity of etiologic agents. As regards the surgical treatment, two groups of cases were recognized. Group 1 comprises 7 patientes with symptoms of a space-occupying lesion; in these patients craniotomies were perfomed with good results. Group 2 included the remainder 28 cases with acquired hydrocephalus. In this group differents methods for ventricular drainage were used, but ventriculo-auriculostomy and specially ventriculo

  10. Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension.

    Science.gov (United States)

    Maston, Levi D; Jones, David T; Giermakowska, Wieslawa; Howard, Tamara A; Cannon, Judy L; Wang, Wei; Wei, Yongyi; Xuan, Weimin; Resta, Thomas C; Gonzalez Bosc, Laura V

    2017-05-01

    Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4 + T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4 + T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination-activating gene 1 knockout mice (RAG1 -/- , lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4 + , CD8 + , or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1 -/- mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4 + but not CD8 + T cells restored the hypertensive phenotype in RAG1 -/- mice. Interestingly, RAG1 -/- mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4 + cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension. Copyright © 2017 the American Physiological Society.

  11. The Effect of Repeated Electroacupuncture Analgesia on Neurotrophic and Cytokine Factors in Neuropathic Pain Rats

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    Junying Wang

    2016-01-01

    Full Text Available Chronic pain is a common disability influencing quality of life. Results of previous studies showed that acupuncture has a cumulative analgesic effect, but the relationship with spinal cytokines neurotrophic factors released by astrocytes remains unknown. The present study was designed to observe the effect of electroacupuncture (EA treatment on spinal cytokines neurotrophic factors in chronic neuropathic pain rats. The chronic neuropathic pain was established by chronic constrictive injury (CCI. EA treatment was applied at Zusanli (ST36 and Yanglingquan (GB34 (both bilateral once a day, for 30 min. IL-1β mRNA, TNF-α mRNA, and IL-1 mRNA were detected by quantitative real-time PCR, and the proteins of BDNF, NGF, and NT3/4 were detected by Western blot. The expression levels of cytokines such as IL-1β mRNA, TNF-α mRNA, IL-6 mRNA, and neurotrophic factors such as BDNF, NGF, and NT3/4 in the spinal cord were increased significantly after CCI. The astrocytes released more IL-1β and BDNF after CCI. Repeated EA treatment could suppress the elevated expression of IL-1β mRNA, TNFα mRNA, and BDNF, NGF, and NT3/4 but had no effect on IL-6 mRNA. It is suggested that cytokines and neurotrophic factors which may be closely associated with astrocytes participated in the process of EA relieving chronic pain.

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

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

    2013-10-01

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

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

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    Balaji P Duraisamy

    2011-01-01

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

  14. MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain.

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    Wang, Conghui; Jiang, Qi; Wang, Min; Li, Dong

    2015-01-01

    We aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and acetone induced cold allodynia, were performed to evaluate the pain threshold. Besides, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of miR-19a and western blotting was carried out to measure the expression of SOCS1. miR-19a expression levels were markedly increased in neuropathic pain models. Moreover, miR-19a significantly attenuated mechanical allodynia and thermal hyperalgesia, and similar results were obtained after knockdown of SOCS1 expression. However, miR-19a markedly increased the times that the rats appeared a sign of cold allodynia, and knockdown of SOCS1 expression had similar effects. Besides, the results of bioinformatics analysis and western blotting analysis were all confirmed that SOCS1 was a direct target of miR-19a in neuropathic pain models. Our finding indicate that SOCS1 is a direct target of miR-19a in neuropathic pain rats and miR-19a may play a critical role in regulating of neuropathic pain via targeting SOCS1.

  15. 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.

  16. Chronic kidney disease of nontraditional etiology in Central America: a provisional epidemiologic case definition for surveillance and epidemiologic studies

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    Matthew Lozier

    Full Text Available SYNOPSIS Over the last two decades, experts have reported a rising number of deaths caused by chronic kidney disease (CKD along the Pacific coast of Central America, from southern Mexico to Costa Rica. However, this specific disease is not associated with traditional causes of CKD, such as aging, diabetes, or hypertension. Rather, this disease is a chronic interstitial nephritis termed chronic kidney disease of nontraditional etiology (CKDnT. According to the Pan American Health Organization (PAHO mortality database, there are elevated rates of deaths related to kidney disease in many of these countries, with the highest rates being reported in El Salvador and Nicaragua. This condition has been identified in certain agricultural communities, predominantly among male farmworkers. Since CKD surveillance systems in Central America are under development or nonexistent, experts and governmental bodies have recommended creating standardized case definitions for surveillance purposes to monitor and characterize this epidemiological situation. A group of experts from Central American ministries of health, the U.S. Centers for Disease Control and Prevention (CDC, and PAHO held a workshop in Guatemala to discuss CKDnT epidemiologic case definitions. In this paper, we propose that CKD in general be identified by the standard definition internationally accepted and that a suspect case of CKDnT be defined as a person age < 60 years with CKD, without type 1 diabetes mellitus, hypertensive diseases, and other well-known causes of CKD. A probable case of CKDnT is defined as a suspect case with the same findings confirmed three or more months later.

  17. Ketamine for chronic pain: risks and benefits

    Science.gov (United States)

    Niesters, Marieke; Martini, Christian; Dahan, Albert

    2014-01-01

    The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4–14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. PMID:23432384

  18. Ketamine for chronic pain: risks and benefits.

    Science.gov (United States)

    Niesters, Marieke; Martini, Christian; Dahan, Albert

    2014-02-01

    The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4-14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

  19. Dor neuropática central após lesão medular traumática: capacidade funcional e aspectos sociais Dolor neuropático central después de lesión medular traumática: capacidad funcional y aspectos sociales Central neuropathic pain after traumatic spinal cord injury: functional capacity and social aspects

    OpenAIRE

    Janaina Vall; Violante Augusta Batista Braga

    2005-01-01

    Estudo de caso comparativo com o objetivo de avaliar a capacidade funcional e os aspectos sociais de dois pacientes, ambos com lesão medular traumática, sem e com dor neuropática central associada, respectivamente. Para avaliar a capacidade funcional, foi utilizado como instrumento o Functional Independence Measure ou Escala de Independência Funcional. E para avaliar os aspectos sociais foi construído o ecomapa de cada paciente, preconizado pelo modelo Calgary de avaliação de famílias. Ambos ...

  20. Mitogen activated protein kinase phosphatase-1 prevents the development of tactile sensitivity in a rodent model of neuropathic pain

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    Ndong Christian

    2012-04-01

    Full Text Available Abstract Background Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. Results We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide. Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced pro-inflammatory cytokines and chemokines and the phosphorylated form of p38. Conclusions Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes.

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    Sara Marinelli

    Full Text Available In recent years a growing debate is about whether botulinum neurotoxins are retrogradely transported from the site of injection. Immunodetection of cleaved SNAP-25 (cl-SNAP-25, the protein of the SNARE complex targeted by botulinum neurotoxin serotype A (BoNT/A, could represent an excellent approach to investigate the mechanism of action on the nociceptive pathways at peripheral and/or central level. After peripheral administration of BoNT/A, we analyzed the expression of cl-SNAP-25, from the hindpaw's nerve endings to the spinal cord, together with the behavioral effects on neuropathic pain. We used the chronic constriction injury of the sciatic nerve in CD1 mice as animal model of neuropathic pain. We evaluated immunostaining of cl-SNAP-25 in the peripheral nerve endings, along the sciatic nerve, in dorsal root ganglia and in spinal dorsal horns after intraplantar injection of saline or BoNT/A, alone or colocalized with either glial fibrillar acidic protein, GFAP, or complement receptor 3/cluster of differentiation 11b, CD11b, or neuronal nuclei, NeuN, depending on the area investigated. Immunofluorescence analysis shows the presence of the cl-SNAP-25 in all tissues examined, from the peripheral endings to the spinal cord, suggesting a retrograde transport of BoNT/A. Moreover, we performed in vitro experiments to ascertain if BoNT/A was able to interact with the proliferative state of Schwann cells (SC. We found that BoNT/A modulates the proliferation of SC and inhibits the acetylcholine release from SC, evidencing a new biological effect of the toxin and further supporting the retrograde transport of the toxin along the nerve and its ability to influence regenerative processes. The present results strongly sustain a combinatorial action at peripheral and central neural levels and encourage the use of BoNT/A for the pathological pain conditions difficult to treat in clinical practice and dramatically impairing patients' quality of life.

  3. Chronic cardiovascular disease mortality in mountaintop mining areas of central Appalachian states.

    Science.gov (United States)

    Esch, Laura; Hendryx, Michael

    2011-01-01

    To determine if chronic cardiovascular disease (CVD) mortality rates are higher among residents of mountaintop mining (MTM) areas compared to mining and nonmining areas, and to examine the association between greater levels of MTM surface mining and CVD mortality. Age-adjusted chronic CVD mortality rates from 1999 to 2006 for counties in 4 Appalachian states where MTM occurs (N = 404) were linked with county coal mining data. Three groups of counties were compared: MTM, coal mining but not MTM, and nonmining. Covariates included smoking rate, rural-urban status, percent male population, primary care physician supply, obesity rate, diabetes rate, poverty rate, race/ethnicity rates, high school and college education rates, and Appalachian county. Linear regression analyses examined the association of mortality rates with mining in MTM areas and non-MTM areas and the association of mortality with quantity of surface coal mined in MTM areas. Prior to covariate adjustment, chronic CVD mortality rates were significantly higher in both mining areas compared to nonmining areas and significantly highest in MTM areas. After adjustment, mortality rates in MTM areas remained significantly higher and increased as a function of greater levels of surface mining. Higher obesity and poverty rates and lower college education rates also significantly predicted CVD mortality overall and in rural counties. MTM activity is significantly associated with elevated chronic CVD mortality rates. Future research is necessary to examine the socioeconomic and environmental impacts of MTM on health to reduce health disparities in rural coal mining areas. © 2011 National Rural Health Association.

  4. Political instability, chronic poverty and food production systems in Central Chad

    NARCIS (Netherlands)

    Dijk, van J.W.M.

    2008-01-01

    In many parts of the world long-term political instability combined with frequent droughts results in chronic poverty and high levels of malnutrition and child mortality. Despite the magnitude and importance of the problem in these areas, the relation between political instability, resource tenure

  5. Central Sensitization and Perceived Indoor Climate among Workers with Chronic Upper-Limb Pain

    DEFF Research Database (Denmark)

    Sundstrup, Emil; Jakobsen, Markus D; Brandt, Mikkel

    2015-01-01

    threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain...

  6. Central sensitization and perceived indoor climate among workers with chronic upper-limb pain

    DEFF Research Database (Denmark)

    Sundstrup, Emil; Jakobsen, Markus D.; Brandt, Mikkel

    2015-01-01

    threshold (PPT) was measured in muscles of the arm, shoulder, and lower leg. Cross-sectional associations were determined using general linear models controlled for age, smoking, and job position. The number of indoor climate complaints was twice as high among workers with chronic pain compared with pain...

  7. Chronic copper poisoning and changes in the central nervous system of sheep

    Energy Technology Data Exchange (ETDEWEB)

    Howell, J McM; Blakemore, W F; Gopinath, C; Hall, G A; Parker, J H

    1974-01-01

    Experiments were performed to determine the changes in the brain by both light and electron microscopy at various stages during the production of chronic copper poisoning in sheep. Results indicate that in brain tissue the volume of astrocytic nuclei was significantly greater than that of controls. The swollen astrocytes contained an excess of glycogen, mitochondria, and endoplasmic reticulum.

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

    Science.gov (United States)

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

    2017-08-01

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

  9. Prevalence of acute neuropathic pain after cancer surgery: A prospective study

    Directory of Open Access Journals (Sweden)

    P N Jain

    2014-01-01

    Full Text Available Background and Aims: Acute neuropathic pain (ANP is an under-recognised and under-diagnosed condition and often difficult to treat. If left untreated, it may further transform into persistent post-operative chronic pain leading to a disability. Aims: This prospective study was undertaken on 300 patients to identify the prevalence of ANP in the post-operative period by using a neuropathic pain detection questionnaire tool. Methods: This is an open-label study in which patients with six different types of cancer surgeries (Thoracic, gastro-intestinal, gynae/urology, bone/soft-tissue, head and neck and breast subgroups-50 each were included for painDETECT questionnaire tool on the 2 nd and 7 th day surgery. Results: This study found a 10% point prevalence of ANP. Analysis showed that 25 patients had ′possible′ ANP, the maximum from urological cancer surgery (6 followed by thoracic surgery (5. Five patients were found to have ′positive′ ANP including 2 groin node dissection, 2 hemipelvectomy and 1 oesophagectomy. Conclusion: Significant relationship between severity of post-operative pain was found with the occurrence of ANP in the post-operative period requiring a special attention to neuropathic pain assessment. Larger studies are required with longer follow-up to identify accurately the true prevalence and causative factors of ANP after surgery.

  10. Identifying Predictors of Central Sleep Apnea/Cheyne-Stokes Breathing in Chronic Heart Failure: a Pathophysiological Approach

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    Draganova Aneliya I.

    2016-12-01

    Full Text Available Chronic heart failure (CHF is a major health problem associated with increased mortality, despite modern treatment options. Central sleep apnea (CSA/Cheyne-Stokes breathing (CSB is a common and yet largely under-diagnosed co-morbidity, adding significantly to the poor prognosis in CHF because of a number of acute and chronic effects, including intermittent hypoxia, sympathetic overactivation, disturbed sleep architecture and impaired physical tolerance. It is characterized by repetitive periods of crescendo-decrescendo ventilatory pattern, alternating with central apneas and hypopneas. The pathogenesis of CSA/CSB is based on the concept of loop gain, comprising three major components: controller gain, plant gain and feedback gain. Laboratory polysomnography, being the golden standard for diagnosing sleep-disordered breathing (SDB at present, is a costly and highly specialized procedure unable to meet the vast diagnostic demand. Unlike obstructive sleep apnea, CSA/CSB has a low clinical profile. Therefore, a reliable predictive system is needed for identifying CHF patients who are most likely to suffer from CSA/CSB, optimizing polysomnography use. The candidate predictors should be standardized, easily accessible and low-priced in order to be applied in daily medical routine.

  11. NMDA receptor antagonists for the treatment of neuropathic pain

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2018-05-01

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

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

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    Rui-Rui Wang

    2018-01-01

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

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

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    Sedghi Goyaghaj N

    2015-11-01

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

  15. Neuropathic pain prevalence following spinal cord injury: A systematic review and meta-analysis.

    Science.gov (United States)

    Burke, D; Fullen, B M; Stokes, D; Lennon, O

    2017-01-01

    Following spinal cord injury (SCI), chronic pain is a common secondary complication with neuropathic pain (NP) cited as one of the most distressing and debilitating conditions leading to poor quality of life, depression and sleep disturbances. Neuropathic pain presenting at or below the level of injury is largely refractory to current pharmacological and physical treatments. No consensus on the prevalence of NP post SCI currently exists, hence this systematic review was undertaken. The review comprised three phases: a methodological assessment of databases [PubMed, Embase, Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library and Physiotherapy Evidence Database (PEDro)] identifying potential papers and screening for inclusion criteria by two independent reviewers; data extraction; and finally rating of internal validity and strength of the evidence, using a published valid and reliable scale. Meta-analysis estimated pooled point prevalence rates using a random effects model. In total, 17 studies involving 2529 patients were included in the review. Overall point prevalence rates for NP were established at 53% (38.58-67.47); 19% (13.26-26.39) for at-level NP and 27% (19.89-34.61) for below-level NP, with high heterogeneity noted (I 2  = 84-93%). Prevalence rates for NP following SCI are high. Future studies should include established definitions, classification systems and assessment tools for NP at defined time points post SCI to follow the trajectory of this problem across the lifespan and include indices of sleep, mood and interference to allow for appropriate, optimal and timely NP management for each patient. WHAT DOES THIS REVIEW ADD?: This is the first systematic review and meta-analysis to record pooled point prevalence of neuropathic pain post spinal cord injury at 53%. Additional pooled analysis shows that neuropathic pain is more common below the level of lesion, in patients with tetraplegia, older patients

  16. Thalamic deep brain stimulation for neuropathic pain after amputation or brachial plexus avulsion.

    Science.gov (United States)

    Pereira, Erlick A C; Boccard, Sandra G; Linhares, Paulo; Chamadoira, Clara; Rosas, Maria José; Abreu, Pedro; Rebelo, Virgínia; Vaz, Rui; Aziz, Tipu Z

    2013-09-01

    Fifteen hundred patients have received deep brain stimulation (DBS) to treat neuropathic pain refractory to pharmacotherapy over the last half-century, but few during the last decade. Deep brain stimulation for neuropathic pain has shown variable outcomes and gained consensus approval in Europe but not the US. This study prospectively evaluated the efficacy at 1 year of DBS for phantom limb pain after amputation, and deafferentation pain after brachial plexus avulsion (BPA), in a single-center case series. Patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, 36-Item Short-Form Health Survey (SF-36), Brief Pain Inventory (BPI), and University of Washington Neuropathic Pain Score (UWNPS). Twelve patients were treated over 29 months, receiving contralateral, ventroposterolateral sensory thalamic DBS. Five patients were amputees and 7 had BPAs, all from traumas. A postoperative trial of externalized DBS failed in 1 patient with BPA. Eleven patients proceeded to implantation and gained improvement in pain scores at 12 months. No surgical complications or stimulation side effects were noted. In the amputation group, after 12 months the mean VAS score improved by 90.0% ± 10.0% (p = 0.001), SF-36 by 57.5% ± 97.9% (p = 0.127), UWNPS by 80.4% ± 12.7% (p stimulation demonstrated efficacy at 1 year for chronic neuropathic pain after traumatic amputation and BPA. Clinical trials that retain patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.

  17. Advancing Nursing Practice: Management of Neuropathic Pain With Capsaicin 8% Without Physician Supervision.

    Science.gov (United States)

    O'Brien, Joanne; Keaveny, Joseph; Pollard, Valerie; Nugent, Linda Elizabeth

    The purpose of this study was to examine the management of patient's neuropathic pain with capsaicin 8% in a nurse-led clinic when administered by 1 registered advanced nurse practitioner without physician supervision. A longitudinal, single-group, descriptive research design was used to assess pain scores and quality of life 3 times over 3 months after treatment. Patients with a diagnosis of neuropathic pain were assessed and treated with capsaicin 8% by 1 advanced nurse practitioner with prescriptive authority in a nurse-led clinic. Pain scores were collected at baseline, and self-assessed pain, activity level, and quality of life were assessed at 1 week, 4 weeks, and 3 months after treatment. Twenty-four patients were recruited, and data were analyzed using Friedman's test. In post hoc analysis, Wilcoxon signed-rank test was used with Bonferroni correction. Pain scores differed from pretreatment to posttreatment at each of the 3 time points, at rest (χ3 = 20.54, P = .001) and on movement (χ3 = 23.644, P = .001), and remained significant after Bonferroni correction. Overall, 62.5% (n = 15) of patients achieved at least a 30% reduction in self-reported pain at rest from pretreatment to 3 months, and 54% (n = 13) achieved the same reduction in pain on movement. Most improvements in patient's quality of life occurred between 1 and 4 weeks. Patient satisfaction was high, with 83% stating that they would be happy to have the treatment repeated. Single-dose capsaicin 8% decreased neuropathic pain after being administered in an outpatient setting by an experienced registered advanced nurse practitioner. Further multicenter research led by advanced nurse practitioners is needed to support high-quality, safe treatment of neuropathic pain with high-concentration capsaicin in nurse-led chronic pain clinics.

  18. Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice.

    Science.gov (United States)

    Yang, Pao-Pao; Yeh, Geng-Chang; Huang, Eagle Yi-Kung; Law, Ping-Yee; Loh, Horace H; Tao, Pao-Luh

    2015-09-22

    Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model. Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α). Co-administration of DM10 potentiated these effects of oxycodone. The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.

  19. Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet.

    Science.gov (United States)

    Dubinion, John H; da Silva, Alexandre A; Hall, John E

    2011-04-01

    Obesity has been suggested to induce selective leptin resistance whereby leptin's anorexic effects are attenuated, whereas the effects to increase sympathetic nervous system activity and blood pressure remain intact. Most studies, however, have tested only the acute responses to leptin administration. This study tested whether feeding a high-fat diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. Sprague-Dawley rats were fed high-fat diet (40% kcal from fat, n=5) or normal-fat diet (13% kcal from fat, n=5) for a year. Radiotelemeters were implanted for continuous monitoring of mean arterial pressure (MAP) and heart rate (HR). A 21G steel cannula was implanted in the lateral cerebral ventricle [intracerebroventricular (ICV)]. After recovery, leptin was infused ICV at 0.02 μg/kg per min for 10 days. High-fat rats were heavier than normal-fat rats (582±12 vs. 511±19 g) and exhibited significantly higher MAP (114±3 vs. 96±7 mmHg). Although the acute (24 h) effects of leptin were attenuated in high-fat rats, chronic ICV leptin infusion decreased caloric intake in both groups similarly (50±8 vs. 40±10%) by day 5. Despite decreased food intake and weight loss, leptin infusion significantly increased MAP and HR in both high-fat and normal-fat rats (7±2 and 5±1 mmHg; 18±11 and 21±10 b.p.m., respectively). These results suggest that obesity induced by feeding a high-fat diet blunts the acute anorexic effects of leptin but does not cause significant resistance to the chronic central nervous system effects of leptin on appetite, MAP, or HR.

  20. Magnetic resonance imaging of sequelae of central pontine myelinolysis in chronic alcohol abusers

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Kudo, Sho [Department of Radiology, Saga Medical School, 5-1-1 Nabeshima, 849-8501, Saga (Japan); Yuzuriha, Takefumi; Murakami, Masaru; Endoh, Koichi; Hiejima, Shigeto; Koga, Hiroshi [Center for Emotional and Behavional Disorders, Hizen National Hospital, 160 Mitsu, Higashisefuri, Kanzaki, 842-0192, Saga (Japan)

    2003-12-01

    Central pontine myelinolysis (CPM) is one of the serious neurological complications of alcoholism. This study evaluated magnetic resonance images of sequelae of CPM. Approximately 600 alcoholic patients were examined by a 1.0-T magnetic resonance imaging device, and 11 patients were retrospectively found to have a central pontine lesion, a presumed sequela of CPM. The lesions had various shapes and most were cavitary. In 3 of the 11 patients bilateral symmetrical oval lesions were faintly visible in the middle cerebellar peduncles. These middle cerebellar peduncular lesions were diagnosed as having Wallerian degeneration of the pontocerebellar tract secondary to CPM. (orig.)

  1. Select tissue mineralconcentrations and chronic wasting disease status in mule deer from north-central Colorado

    OpenAIRE

    Wolfe, Lisa L.; Conner, Mary M.; Bedwell, Cathy L.; Lukacs, Paul M.; Miller, Michael W.

    2010-01-01

    Trace mineral imbalances have been suggested as having a causative or contributory role in chronic wasting disease (CWD), a prion disease of several North American cervid species. To begin exploring relationships between tissue mineral concentrations and CWD in natural systems, we measured liver tissue concentrations of copper, manganese, and molybdenum in samples from 447 apparently healthy, adult (≥2 yr old) mule deer (Odocoileus hemionus) culled or vehicle killed from free-ranging populati...

  2. The multi-level impact of chronic intermittent hypoxia on central auditory processing.

    Science.gov (United States)

    Wong, Eddie; Yang, Bin; Du, Lida; Ho, Wai Hong; Lau, Condon; Ke, Ya; Chan, Ying Shing; Yung, Wing Ho; Wu, Ed X

    2017-08-01

    During hypoxia, the tissues do not obtain adequate oxygen. Chronic hypoxia can lead to many health problems. A relatively common cause of chronic hypoxia is sleep apnea. Sleep apnea is a sleep breathing disorder that affects 3-7% of the population. During sleep, the patient's breathing starts and stops. This can lead to hypertension, attention deficits, and hearing disorders. In this study, we apply an established chronic intermittent hypoxemia (CIH) model of sleep apnea to study its impact on auditory processing. Adult rats were reared for seven days during sleeping hours in a gas chamber with oxygen level cycled between 10% and 21% (normal atmosphere) every 90s. During awake hours, the subjects were housed in standard conditions with normal atmosphere. CIH treatment significantly reduces arterial oxygen partial pressure and oxygen saturation during sleeping hours (relative to controls). After treatment, subjects underwent functional magnetic resonance imaging (fMRI) with broadband sound stimulation. Responses are observed in major auditory centers in all subjects, including the auditory cortex (AC) and auditory midbrain. fMRI signals from the AC are statistically significantly increased after CIH by 0.13% in the contralateral hemisphere and 0.10% in the ipsilateral hemisphere. In contrast, signals from the lateral lemniscus of the midbrain are significantly reduced by 0.39%. Signals from the neighboring inferior colliculus of the midbrain are relatively unaffected. Chronic hypoxia affects multiple levels of the auditory system and these changes are likely related to hearing disorders associated with sleep apnea. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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    Ouyang Handong

    2011-05-01

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

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

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    Ombretta Caspani

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

  5. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala

    DEFF Research Database (Denmark)

    Varodayan, Florence P.; Soni, Neeraj; Bajo, Michal

    2016-01-01

    release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1...

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

    Science.gov (United States)

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

    2016-06-01

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

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

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    Sumizono M

    2018-02-01

    Full Text Available Megumi Sumizono,1,2 Harutoshi Sakakima,1 Shotaro Otsuka,1 Takuto Terashi,1 Kazuki Nakanishi,1,2 Koki Ueda,1,2 Seiya Takada,1,2 Kiyoshi Kikuchi3 1Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan; 2Kirishima Orthopedics, Kirishima, Japan; 3Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Kurume, Japan Background: Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI model. Materials and methods: Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group, CCI and low-frequency exercise (LFE group, CCI and no exercise (No-Ex group, and naive animals (control group. Rats ran on a treadmill, at a speed of 20 m/min, for 30 min, for 5 (HFE or 3 (LFE days a week, for a total of 5 weeks. The 50% withdrawal threshold was evaluated for mechanical sensitivity. The activation of glial cells (microglia and astrocytes, expression of brain-derived neurotrophic factor (BDNF and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone were administered using intraperitoneal injection. Results: The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic pain showed the highest level of mechanical hypersensitivity at 2 weeks, which improved slightly until 5 weeks after CCI. In both exercise groups, the alleviation of

  8. Neuropathic pain and use of PainDETECT in patients with fibromyalgia: a cohort study.

    Science.gov (United States)

    Gauffin, Jarno; Hankama, Tiina; Kautiainen, Hannu; Hannonen, Pekka; Haanpää, Maija

    2013-02-14

    Fibromyalgia has a plethorae of symptoms, which can be confusing and even misleading. Accurate evaluation is necessary when patients with fibromyalgia are treated. Different types of instruments are available for the clinicians to supplement evaluation. Our objective was to study the applicability of the PainDETECT instrument to screen neuropathic pain in patients with fibromyalgia. 158 patients with primary fibromyalgia underwent a neurological examination including bedside sensory testing. They also fulfilled four questionnaires: PainDETECT, Beck depression inventory IA (BDI IA), Fibromyalgia Impact Questionnaire (FIQ) and a self-made questionnaire regarding present pain and pain relieving methods of the patients. The results of the clinical evaluation and questionnaires were then compared. Clinically verified neuropathic pain was diagnosed in 53/158 [34% (95% Cl: 26 to 41)] patients. The ROC curve achieved a maximum Youden´s index at score of 17 when sensitivity was 0.79 (95% Cl: 0.66 to 0.89) and specificity 0.53 (95% Cl: 0.43 to 0.63). The PainDETECT total score (OR: 1.14 95% Cl: 1.06 to 1.22), FM as the worst current pain (OR: 0.31; 95% 0.16 to 0.62), body mass index (BMI) (OR: 1.05; 95% Cl: 1.00 to 1.11) and the intensity of current pain (OR: 1.20; 95% Cl: 1.01 to 1.41) were significantly associated with the presence of neuropathic pain in univariate analyses. This study highlights the importance of thorough clinical examination. The Neuropathic pain screening tool PainDETECT is not as useful in patients with fibromyalgia as in patients with uncompromised central pain control.

  9. Neuropathic pain and use of PainDETECT in patients with fibromyalgia: a cohort study

    Directory of Open Access Journals (Sweden)

    Gauffin Jarno

    2013-02-01

    Full Text Available Abstract Backround Fibromyalgia has a plethorae of symptoms, which can be confusing and even misleading. Accurate evaluation is necessary when patients with fibromyalgia are treated. Different types of instruments are available for the clinicians to supplement evaluation. Our objective was to study the applicability of the PainDETECT instrument to screen neuropathic pain in patients with fibromyalgia. Methods 158 patients with primary fibromyalgia underwent a neurological examination including bedside sensory testing. They also fulfilled four questionnaires: PainDETECT, Beck depression inventory IA (BDI IA, Fibromyalgia Impact Questionnaire (FIQ and a self-made questionnaire regarding present pain and pain relieving methods of the patients. The results of the clinical evaluation and questionnaires were then compared. Results Clinically verified neuropathic pain was diagnosed in 53/158 [34% (95% Cl: 26 to 41] patients. The ROC curve achieved a maximum Youden´s index at score of 17 when sensitivity was 0.79 (95% Cl: 0.66 to 0.89 and specificity 0.53 (95% Cl: 0.43 to 0.63. The PainDETECT total score (OR: 1.14 95% Cl: 1.06 to 1.22, FM as the worst current pain (OR: 0.31; 95% 0.16 to 0.62, body mass index (BMI (OR: 1.05; 95% Cl: 1.00 to 1.11 and the intensity of current pain (OR: 1.20; 95% Cl: 1.01 to 1.41 were significantly associated with the presence of neuropathic pain in univariate analyses. Conclusion This study highlights the importance of thorough clinical examination. The Neuropathic pain screening tool PainDETECT is not as useful in patients with fibromyalgia as in patients with uncompromised central pain control.

  10. Microsurgical Drezotomy for Neuropathic Pain after Spinal Cord Injury: Long Term Results in a Patient

    OpenAIRE

    Acevedo González, Juan Carlos; López Cárdenas, Gloria Viviana; Berbeo Calderón, Miguel Enrique; Zorro Guio, Óscar; Díaz Orduz, Roberto Carlos; Feo Lee, Óscar

    2012-01-01

    70 % of patients with spinal cord injuries are chronic and disabling neuropathic pain. This article presents the 23 years-old patient case, who suffered an infrasegmentary severe pain by spinal cord trauma. We performed neurosurgical treatment of pain. Drezotomy is selective section of nociceptive fibers in the spinal segments involved. The patient has 24 months of complete improvement and discontinuation of analgesics. Un 70 % de pacientes con lesión medular tiene dolor neuropático crónic...

  11. Longitudinal Structural and Functional Brain Network Alterations in a Mouse Model of Neuropathic Pain.

    Science.gov (United States)

    Bilbao, Ainhoa; Falfán-Melgoza, Claudia; Leixner, Sarah; Becker, Robert; Singaravelu, Sathish Kumar; Sack, Markus; Sartorius, Alexander; Spanagel, Rainer; Weber-Fahr, Wolfgang

    2018-04-22

    Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery. A progressive development and potentiation of stimulus-evoked pain responses (cold and mechanical allodynia) were detected during the course of pain chronification. Voxel-based morphometry demonstrated striking decreases in volume following pain induction in all brain sites assessed - an effect that reversed over time. Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Chronic inorganic mercury exposure induces sex-specific changes in central TNFα expression: Importance in autism?

    OpenAIRE

    Curtis, J. Thomas; Chen, Yue; Buck, Daniel J.; Davis, Randall L.

    2011-01-01

    Mercury is neurotoxic and increasing evidence suggests that environmental exposure to mercury may contribute to neuropathologies including Alzheimer's disease and autism spectrum disorders. Mercury is known to disrupt immunocompetence in the periphery, however, little is known about the effects of mercury on neuroimmune signaling. Mercury-induced effects on central immune function are potentially very important given that mercury exposure and neuroinflammation both are implicated in certain n...

  13. Central and peripheral effects of chronic food restriction and weight restoration in the rat.

    Science.gov (United States)

    Kinzig, Kimberly P; Hargrave, Sara L; Tao, Erin E

    2009-02-01

    Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

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

    Science.gov (United States)

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

    2016-08-01

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

  15. [Correlations of central nervous system and thyroid function under chronic emotional stress].

    Science.gov (United States)

    Amiragova, M G; Arkhangel'skaia, M I

    1982-06-01

    Experiments on cats exposed to chronic emotional stress induced during one week by 4-hour immobilization of the animals in conjunction with aperiodic electrocutaneous stimulation were made to study correlations of the time course of changes in the EEG of the cortical and subcortical structures and the content of thyroxin in the peripheral blood at varying time of the experiments. It was demonstrated that in the course of stress, the EEG manifests the cycles of "burst" activity of slow waves, which are first recorded in the posterior hypothalamus and then get generalized. This is accompanied by a significantly high thyroxin secretion. As the stress exposures are repeated, the EEG changes become dominant, also corresponding with high thyroxin secretion. After the experiments are over, the cycles of "burst" activity accompanied by enhanced thyroid function are still recordable over several days.

  16. The Central Role of the Gut Microbiota in Chronic Inflammatory Diseases

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    Caroline Marcantonio Ferreira

    2014-01-01

    Full Text Available The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.

  17. Central thalamic deep brain stimulation to promote recovery from chronic posttraumatic minimally conscious state: challenges and opportunities.

    Science.gov (United States)

    Giacino, Joseph; Fins, Joseph J; Machado, Andre; Schiff, Nicholas D

    2012-07-01

    Central thalamic deep brain stimulation (CT-DBS) may have therapeutic potential to improve behavioral functioning in patients with severe traumatic brain injury (TBI), but its use remains experimental. Current research suggests that the central thalamus plays a critical role in modulating arousal during tasks requiring sustained attention, working memory, and motor function. The aim of the current article is to review the methodology used in the CT-DBS protocol developed by our group, outline the challenges we encountered and offer suggestions for future DBS trials in this population. RATIONAL FOR CT-DBS IN TBI:  CT-DBS may therefore be able to stimulate these functions by eliciting action potentials that excite thalamocortical and thalamostriatal pathways. Because patients in chronic minimally conscious state (MCS) have a very low probability of regaining functional independence, yet often have significant sparing of cortical connectivity, they may represent a particularly appropriate target group for CT-DBS. PIlOT STUDY RESULTS:  We have conducted a series of single-subject studies of CT-DBS in patients with chronic posttraumatic MCS, with 24-month follow-up. Outcomes were measured using the Coma Recovery Scale-Revised as well as a battery of secondary outcome measures to capture more granular changes. Findings from our index case suggest that CT-DBS can significantly increase functional communication, motor performance, feeding, and object naming in the DBS on state, with performance in some domains remaining above baseline even after DBS was turned off. The use of CT-DBS in patients in MCS, however, presents challenges at almost every step, including during surgical planning, outcome measurement, and postoperative care. Additionally, given the difficulties of obtaining informed consent from patients in MCS and the experimental nature of the treatment, a robust, scientifically rooted ethical framework is resented for pursuing this line of work. © 2012

  18. Safety and feasibility of chronic transvenous phrenic nerve stimulation for treatment of central sleep apnea in heart failure patients.

    Science.gov (United States)

    Zhang, Xilong; Ding, Ning; Ni, Buqing; Yang, Bing; Wang, Hong; Zhang, Shi-Jiang

    2017-03-01

    Central sleep apnea (CSA) is common in patients with heart failure (HF) and is associated with poor quality of life and prognosis. Early acute studies using transvenous phrenic nerve stimulation (PNS) to treat CSA in HF have shown a significantly reduction of CSA and improvement of key polysomnographic parameters. In this study, we evaluated the safety of and efficiency chronic transvenous PNS with an implanted neurostimulator in HF patients with CSA. This study was a prospective, nonrandomized evaluation of unilateral transvenous PNS in eight HF patients with CSA. The stimulation lead, which connected to a proprietary neurostimulator, was positioned in either the left pericardiophrenic or right brachiocephalic vein. Monitoring during implantation and 6-monthly follow-ups were performed. Six of the implanted eight patients completed the study (one was lost to follow-up; one died from pneumonia). Neither side effects nor adverse events related to stimulation occurred. During the 6-monthly follow-ups, one patient had a lead dislodgement in the first month and the lead was subsequently repositioned. No additional lead dislodgements occurred. There were no significant changes in sleep habits, appetite, bleeding or infections. Compared with the parameters before stimulator implantation, there were significant improvement in apnea-hypopnea index, central apnea index, left ventricular ejection fraction and 6-min walk distance (all P < 0.01). Use of chronic transvenous PNS appears to be safe and feasible in HF patients with CSA. Large multicenter studies are needed to confirm safety and efficacy in this population. © 2015 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Sakamoto Atsuhiro

    2011-01-01

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

  20. Central pontine myelinolysis in a chronic alcoholic: A clinical and brain magnetic resonance imaging follow-up

    Directory of Open Access Journals (Sweden)

    Dujmović Irena

    2013-01-01

    Full Text Available Introduction. Central pontine myelinolysis (CPM is a noninflammatory, demyelinating lesion usually localised in the basis pontis. Chronic alcoholism is frequently associated with this condition which may have a variable clinical outcome. Until now, brain magnetic resonance imaging (MRI follow-up in alcoholic CPM cases after alcohol withdrawal has been rarely described. Case report. We reported a 30- year-old male with a 12-year history of alcohol abuse, who presented with inability to stand and walk, nausea, vomiting and somnolence. Neurological examination revealed: impared fixation on lateral gaze, dysarthria, mild spastic quadriparesis, truncal and extremity ataxia, sock-like hypesthesia and moderate decrease in vibration sense in legs. Brain MRI showed a trident-shaped non-enhancing pontine lesion highly suggestive of CPM. After an eight-month alcoholfree follow-up period, the patient’s clinical status significantly improved, while the extent of MRI pontine lesion was merely slightly reduced. Conclusion. The presented case demonstrates that CPM in chronic alcoholics may have a benign clinical course after alcohol withdrawal, which is not necessarily associated with the reduction of lesions on brain MRI. [Projekat Ministarstva nauke Republike Srbije, br. 175031

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

    Science.gov (United States)

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

    2017-10-27

    Neuropathic pain is caused by dysfunction or primary injury of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) play important roles in the development of neuropathic pain. However, the effects of lncRNA colon cancer associated transcript-1 (CCAT1) in neuropathic pain have not been reported. The model of bilateral sciatic nerve chronic constriction injuries (bCCI) is regarded as long-lasting mechanical hypersensitivity and cold allodynia, which is the representative symptom in the human subjects suffering from the neuropathic pain. In this study, we found that CCAT1 expression was decreased in the spinal dorsal horn, dorsal root ganglion (DRG), hippocampus, and anterior cingulate cortex (ACC) of rats with bCCI. The rats of bCCI presented the cold allodynia after the 14 th day of postoperation. We furtherly showed that lncRNA CCAT1 decreased miR-155 expression and enhanced Serum and glucocorticoid regulated protein kinase 3 (SGK3) expression in the NGF-differentiated PC12 cell. We found that miR-155 expression was increased in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. However, SGK3 expression was downregulated in the spinal dorsal horn, DRG, hippocampus, and ACC of rats with bCCI injuries. Moreover, lncRNA CCAT1 overexpression could alleviate the pain thresholds and inhibited expression of SGK3 could rescue this effect. In conclusion, these results suggested the crucial roles of CCAT1 and SGK3 in the neuropathic pain.

  2. Evaluation of the Effect of Duration on the Efficacy of Pulsed Radiofrequency in an Animal Model of Neuropathic Pain.

    Science.gov (United States)

    Ramzy, Eiad A; Khalil, Khaled I; Nour, Eman M; Hamed, Mohammed F; Taha, Mohamed A

    2018-03-01

    Pulsed radiofrequency (PRF) is increasingly used in clinical practice, especially in neuropathic pain disorders. Although PRF is not new to clinical use, there are significant gaps in knowledge regarding its effectiveness. The current study was conducted to evaluate the effect of duration of application of PRF on its analgesic efficacy in improvement of neuropathic pain. A randomized experimental trial. An animal research facility at the College of Veterinary Medicine at Mansoura University in Egypt. Chronic constriction of the sciatic nerve of 36 male Sprague-Dawley rats was performed to induce neuropathic pain. The rats were divided into 6 groups (6 rats each) in which PRF was applied for 2, 4, 6, or 8 minutes or not at all. In one group, RF cannula was applied without performing PRF intervention. The pain was assessed through observation of resting paw posture (RPP) at 3, 10, and 21 days. Nerve damage was assessed by histopathological evaluation of the sciatic nerve. Immunohistochemical localization of proinflammatory cytokines (interleukin 6 [IL-6] and tumor necrosis factor alpha [TNF-alpha]) was also done. RPP was improved in rats treated with PRF. This improvement was significant only in rats treated for 8 minutes. Increased duration for PRF application was associated with a significant decrease in IL-6 and TNF-alpha contents in all groups when compared with the control group. Histopathological evaluation of the constricted sciatic nerve revealed no statistical significance among the different study groups. The study was limited by the lack of measurement of other inflammatory markers that may help elucidate other relevant mechanisms. Increased duration of PRF application resulted in better analgesic efficacy without any increase in tissue injury in an animal model of neuropathic pain. This effect may be attributed to decreased production of pro-inflammatory cytokines. Pulsed radiofrequency, analgesic, rats, sciatic nerve, duration, neuropathic pain.

  3. Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion.

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    Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

    2014-09-01

    Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. © 2014 Associated Professional Sleep Societies, LLC.

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

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

    2015-12-01

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

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

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

    2013-12-01

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

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

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

    2017-01-01

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

  7. Can We Distinguish between Inflammatory and Neuropathic Pain?

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    Gary J Bennett

    2006-01-01

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

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

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    Vickers ER

    2014-05-01

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

  9. Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

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    Hui-Zhong Wen

    2017-06-01

    Full Text Available Background: Transcranial direct current stimulation (tDCS is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters.Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1 on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia.Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI, we measured pain thresholds before and after anodal-tDCS (A-tDCS using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models.Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS and contralateral-tDCS (con-tDCS produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats.Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Frida Kahlo: Portrait of Chronic Pain.

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    Courtney, Carol A; O'Hearn, Michael A; Franck, Carla C

    2017-01-01

    The Mexican artist Frida Kahlo (1907-1954) is one of the most celebrated artists of the 20th century. Although famous for her colorful self-portraits and associations with celebrities Diego Rivera and Leon Trotsky, less known is the fact that she had lifelong chronic pain. Frida Kahlo developed poliomyelitis at age 6 years, was in a horrific trolley car accident in her teens, and would eventually endure numerous failed spinal surgeries and, ultimately, limb amputation. She endured several physical, emotional, and psychological traumas in her lifetime, yet through her art, she was able to transcend a life of pain and disability. Of her work, her self-portraits are conspicuous in their capacity to convey her life experience, much of which was imbued with chronic pain. Signs and symptoms of chronic neuropathic pain and central sensitization of nociceptive pathways are evident when analyzing her paintings and medical history. This article uses a narrative approach to describe how events in the life of this artist contributed to her chronic pain. The purpose of this article is to discuss Frida Kahlo's medical history and her art from a modern pain sciences perspective, and perhaps to increase our understanding of the pain experience from the patient's perspective. © 2017 American Physical Therapy Association.

  12. Glycine transporter GlyT1, but not GlyT2, is expressed in rat dorsal root ganglion--Possible implications for neuropathic pain

    NARCIS (Netherlands)

    Schlösser, Lukas; Barthel, Franziska; Brandenburger, Timo; Neumann, Elena; Bauer, Inge; Eulenburg, Volker; Werdehausen, Robert; Hermanns, Henning

    2015-01-01

    Glycinergic inhibitory neurotransmission plays a pivotal role in the development of neuropathic pain. The glycine concentration in the synaptic cleft is controlled by the glycine transporters GlyT1 and GlyT2. GlyT1 is expressed throughout the central nervous system, while GlyT2 is exclusively

  13. Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients

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    Pierre eGuertin

    2014-05-01

    Full Text Available Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs - from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS networks that are involved in the control of ambulation and other stereotyped motor patterns - specifically Central Pattern Generators (CPGs that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of SCI should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic spinal cord-injured patients.

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

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    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.

  15. Diagnostic value of color doppler ultrasonography in detecting stenosis and occlusion of central veins in patients with chronic kidney disease

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    Masoud Pezeshki Rad

    2015-01-01

    Full Text Available Venography is an invasive diagnostic test that uses contrast material that provides a picture of the condition of the veins. But, complications, including adverse effects on the kidney, do occur. On the other hand, with the current technological development, application of ultrasound in the diagnosis of obstructive diseases of the veins is gaining popularity, being non-invasive, easy to perform and cost-effective. The aim of this study was to evaluate the diagnostic value of Doppler sonography in the diagnosis of central vein stenosis. In this descriptive-analytical study, 41 hemodialysis patients who had been referred for 50 upper limb venographies to the radiology department of Imam Reza (AS were included. Patients with chronic kidney disease with a history of catheterization of the vein, jugular or subclavian, and who had established fistulas or synthetic vascular grafts were targeted. Central venous ultrasound was performed on both sides to evaluate stenosis or occlusion. Venography was performed by the radiologist the next day or the day before hemodialysis. Data on demographic characteristics, findings of clinical examination and findings of ultrasound as well as venography were recorded by using the SPSS software, Chi-square test and Spearman correlation, and Kappa agreement was calculated for sensitivity, specificity and predictive values. Twenty-three (56% patients were male subjects and 18 patients (44% were female. Twenty-three (56% patients of the study population were aged 60 years. The overall sensitivity, specificity and positive predictive value and negative predictive value of Doppler sonography in the proximal veins in hemodialysis patients compared with venography were, respectively, 80.9%, 79.3%, 73.9% and 85.1%. Color Doppler sonography, as a non-invasive method, could be a good alternative for venography in the assessment of the upper limb with central vein stenosis and occlusion.

  16. Diagnostic value of color doppler ultrasonography in detecting stenosis and occlusion of central veins in patients with chronic kidney disease.

    Science.gov (United States)

    Rad, Masoud Pezeshki; Kazemzadeh, Gholam Hosain; Ziaee, Masood; Azarkar, Ghodsieh

    2015-03-01

    Venography is an invasive diagnostic test that uses contrast material that provides a picture of the condition of the veins. But, complications, including adverse effects on the kidney, do occur. On the other hand, with the current technological development, application of ultrasound in the diagnosis of obstructive diseases of the veins is gaining popularity, being non-invasive, easy to perform and cost-effective. The aim of this study was to evaluate the diagnostic value of Doppler sonography in the diagnosis of central vein stenosis. In this descriptive-analytical study, 41 hemodialysis patients who had been referred for 50 upper limb venographies to the radiology department of Imam Reza (AS) were included. Patients with chronic kidney disease with a history of catheterization of the vein, jugular or subclavian, and who had established fistulas or synthetic vascular grafts were targeted. Central venous ultrasound was performed on both sides to evaluate stenosis or occlusion. Venography was performed by the radiologist the next day or the day before hemodialysis. Data on demographic characteristics, findings of clinical examination and findings of ultrasound as well as venography were recorded by using the SPSS software, Chi-square test and Spearman correlation, and Kappa agreement was calculated for sensitivity, specificity and predictive values. Twenty-three (56%) patients were male subjects and 18 patients (44%) were female. Twenty-three (56%) patients of the study population were aged 60 years. The overall sensitivity, specificity and positive predictive value and negative predictive value of Doppler sonography in the proximal veins in hemodialysis patients compared with venography were, respectively, 80.9%, 79.3%, 73.9% and 85.1%. Color Doppler sonography, as a non-invasive method, could be a good alternative for venography in the assessment of the upper limb with central vein stenosis and occlusion.

  17. Flow cytometry analysis of inflammatory cells isolated from the sciatic nerve and DRG after chronic constriction injury in mice.

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    Liu, Liping; Yin, Yan; Li, Fei; Malhotra, Charvi; Cheng, Jianguo

    2017-06-01

    Cellular responses to nerve injury play a central role in the pathogenesis of neuropathic pain. However, the analysis of site specific cellular responses to nerve injury and neuropathic pain is limited to immunohistochemistry staining with numerous limitations. We proposed to apply flow cytometry to overcome some of the limitations and developed two protocols for isolation of cells from small specimens of the sciatic nerve and dorsal root ganglion (DRG) in mice. RESULTS AND COMPARASION WITH EXISTING: methods We found that both the non-enzymatic and enzymatic approaches were highly effective in harvesting a sufficient number of cells for flow cytometry analysis in normal and pathological conditions. The total number of cells in the injury site of the sciatic and its DRGs increased significantly 14days after chronic constriction injury (CCI) of the sciatic nerve, compared to sham surgery control or the contralateral control. The enzymatic approach yielded a significantly higher total number of cells and CD45 negative cells, suggesting that this approach allows for harvest of more resident cells, compared to the non-enzymatic method. The percentage of CD45 + /CD11b + cells was significantly increased in the sciatic nerve but not in the DRG. These results were consistent with both protocols. We thus offer two simple and effective protocols that allow for application of flow cytometry to the investigation of cellular and molecular mechanisms of neuropathic pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. A behavioral and pharmacological validation of the acetone spray test in gerbils with a chronic constriction injury.

    NARCIS (Netherlands)

    Vissers, K.C.P.; Meert, T.F.

    2005-01-01

    Cold and mechanical allodynia are important symptoms in patients with neuropathic pain. The study of cold allodynia in animals can help us to understand the underlying pathophysiological mechanisms of neuropathic pain and to validate drugs. The evaluation of cold allodynia in gerbils with a chronic

  19. Spinal NF-κB and chemokine ligand 5 expression during spinal glial cell activation in a neuropathic pain model.

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    Qin Yin

    Full Text Available BACKGROUND: The NF-κB pathway and chemokine (C-C motif ligand 5 (CCL5 are involved in pain modulation; however, the precise mechanisms of their interactions in chronic neuropathic pain have yet to be established. METHODS: The present study examined the roles of spinal NF-κB and CCL5 in a neuropathic pain model after chronic constriction injury (CCI surgery. CCI-induced pain facilitation was evaluated using the Plantar and von Frey tests. The changes in NF-κB and CCL5 expression were analyzed by immunohistochemistry and Western blot analyses. RESULTS: Spinal NF-κB and CCL5 expression increased after CCI surgery. Repeated intrathecal infusions of pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor decreased CCL5 expression, inhibited the activation of microglia and astrocytes, and attenuated CCI-induced allodynia and hyperalgesia. Intrathecal injection of a CCL5-neutralizing antibody attenuated CCI-induced pain facilitation and also suppressed spinal glial cell activation after CCI surgery. However, the CCL5-neutralizing antibody did not affect NF-κB expression. Furthermore, selective glial inhibitors, minocycline and fluorocitrate, attenuated the hyperalgesia induced by intrathecal CCL5. CONCLUSIONS: The inhibition of spinal CCL5 expression may provide a new method to prevent and treat nerve injury-induced neuropathic pain.

  20. Prevalence of Neuropathic Pain and the Need for Treatment

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    Pat Morley-Forster

    2006-01-01

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

  1. Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex

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    Ruohe Zhao

    2018-04-01

    Full Text Available The anterior cingulate cortex (ACC is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5 pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.

  2. Animal model of neuropathic tachycardia syndrome

    Science.gov (United States)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2012-12-01

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

  4. An Algorithm for Neuropathic Pain Management in Older People

    OpenAIRE

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

    2016-01-01

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

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

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    Elphick Maurice R

    2009-07-01

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

  6. 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.

  7. Cross-Cultural Psychometric Assessment of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale in the Portuguese Population.

    Science.gov (United States)

    Barbosa, Margarida; Bennett, Michael I; Verissimo, Ramiro; Carvalho, Davide

    2014-09-01

    Chronic pain is a well-known phenomenon. The differential diagnosis between neuropathic and nociceptive pain syndromes is a challenge. Consequently, assessment instruments that can distinguish between these conditions in a standardized way are of the utmost importance. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) is a screening tool developed to identify chronic neuropathic pain. The aim of this study was the Portuguese language translation, linguistic adaptation of the LANSS pain scale, its semantic validation, internal consistency, temporal stability, as well its validity and discriminative power. LANSS Portuguese version scale was applied to 165 consecutive patients attending the pain clinic: 103 fulfilled the clinical criteria for the diagnosis of pain of neuropathic origin and the remaining 62 fulfilled the criteria for nociceptive pain. The scale proved to be an internally consistent (Cronbach's alpha = 0.78) and reliable instrument with good test-retest stability (r = 0.7; P cross-cultural version is a reliable and valid instrument for the differentiation of this type of pain. Its usage is recommended. © 2013 World Institute of Pain.

  8. Sonographic findings predictive of central lymph node metastasis in patients with papillary thyroid carcinoma: influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography.

    Science.gov (United States)

    Yoo, Yeon Hwa; Kim, Jeong-Ah; Son, Eun Ju; Youk, Ji Hyun; Kwak, Jin Young; Kim, Eun-Kyung; Park, Cheong Soo

    2013-12-01

    To analyze sonographic findings suggesting central lymph node metastasis of papillary thyroid carcinoma and to evaluate the influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography for predicting central lymph node metastasis. A total of 124 patients (101 female and 23 male; mean age, 47.5 years; range, 21-74 years) underwent sonographically guided fine-needle aspiration in central lymph nodes from January 2008 to July 2011. Sonographic features of size, shape, margin, thickening of the cortex, cortical echogenicity, presence of a hilum, cystic changes, calcification, and vascularity of enlarged lymph nodes were analyzed before fine-needle aspiration and classified into 2 categories (probably benign and suspicious). Sonographic findings were correlated with the pathologic diagnosis and associated chronic lymphocytic thyroiditis. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance of sonography for predicting central lymph node metastasis according to the associated thyroiditis. Fifty-one lymph nodes (39.5%) were malignant, and 73 (60.5%) were benign. On univariate analysis, size, shape, margin, cortical thickening, cortical echogenicity, cystic changes, calcification, and vascularity were significantly different between the benign and metastatic nodes (P thyroiditis-positive patients and 0.971 (95% CI, 0.938-1.000) in negative patients. Eccentric cortical thickening and cortical hyperechogenicity were the sonographic findings predictive of central lymph node metastasis from papillary thyroid carcinoma. The diagnostic performance of sonography for predicting metastasis was superior in chronic lymphocytic thyroiditis-negative patients than in positive patients.

  9. Validation of the Malayalam version of Leeds assessment of neuropathic symptoms and signs pain scale in cancer patients in the Regional Cancer Centre, Thiruvananthapuram, Kerala, India

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    Shoukkathali Anzar

    2017-01-01

    Full Text Available Objective: The Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS is a 7-item self-report scale developed to identify pain which is of predominantly neuropathic origin. The aim of this study was to develop a Malayalam version of the LANSS and to test its validity and reliability in chronic pain patients. Methodology: We enrolled 101 Malayalam-speaking chronic pain patients who visited the Division of Palliative Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala, India. The translated version of S- LANSS was constructed by standard means. Fifty-one neuropathic pain and fifty nociceptive pain patients were identified by an independent pain physician and were subjected to the new pain scale by a palliative care nurse who was blinded to the diagnosis. The “gold standard diagnosis” is what the physician makes after clinical examination. Its validation, sensitivity, specificity, and positive and negative predictive values were determined. Results: Fifty-one neuropathic pain and fifty nociceptive pain patients were subjected to the Malayalam version of S-LANSS pain scale for validity testing. The agreement by Cohen's Kappa 0.743, Chi-square test P < 0.001, sensitivity 89.58, specificity 84.91, positive predictive value 84.31, negative predictive value 90.00, accuracy by 87.13, and likelihood ratio 5.94. Conclusion: The Malayalam version of S-LANSS pain scale is a validated screening tool for identifying neuropathic pain in chronic pain patients in Malayalam-speaking regions.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  13. Neonicotinoid concentrations in urine from chronic kidney disease patients in the North Central Region of Sri Lanka.

    Science.gov (United States)

    Kabata, Risako; Nanayakkara, Shanika; Senevirathna, Stmld; Harada, Kouji H; Chandrajith, Rohana; Hitomi, Toshiaki; Abeysekera, Tilak; Takasuga, Takumi; Koizumi, Akio

    2016-01-01

    Neonicotinoid insecticides have been widely used around the world since the 1990s. Reports have been made since the 1990s of rice paddy farmers in the North Central Region (NCR) of Sri Lanka suffering from chronic kidney disease with unknown etiology (CKDu). A preliminary evaluation of the exposure of local farmers in the NCR of Sri Lanka to neonicotinoids was performed. We analyzed neonicotinoid and neonicotinoid metabolite concentrations in spot urine samples. We selected 40 samples, 10 from farmers with CKDu and 10 from controls from each of two areas, Medawachchiya and Girandurukotte. Imidacloprid and desmethyl-acetamiprid were found at significantly higher concentrations in the control samples (with medians of 51 ng/l and 340 ng/l, respectively) than in the CKDu samples (medians of 15 ng/l and 150 ng/l, respectively) when the results were not adjusted for the creatinine contents. None of the six compounds that were measured in the urine samples were found at significantly higher concentrations in the CKDu samples than in the control samples. None of the neonicotinoid concentrations in the samples analyzed in this study exceeded the concentrations that have been found in samples from the general population of Japan. Farmers (both with and without CKDu) living in CKDu-endemic areas in the NCR of Sri Lanka are exposed to lower neonicotinoid concentrations than non-occupationally exposed residents of Japan.

  14. 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.

  15. The relationship between chronic lymphocytic thyroiditis and central neck lymph node metastasis in North American patients with papillary thyroid carcinoma.

    Science.gov (United States)

    Jara, Sebastian M; Carson, Kathryn A; Pai, Sara I; Agrawal, Nishant; Richmon, Jeremy D; Prescott, Jason D; Dackiw, Alan; Zeiger, Martha A; Bishop, Justin A; Tufano, Ralph P

    2013-12-01

    Several studies have reported that concurrent chronic lymphocytic thyroiditis (CLT) with papillary thyroid carcinoma (PTC) is associated with improved prognosis of the PTC, including decreased lymph node metastasis. We sought to assess the incidence of central nodal metastasis (CNM) in patients with PTC and concurrent CLT. We studied 495 consecutive patients who underwent thyroidectomy with nodal excision for PTC. Pathology reports identified the presence of CLT and the extent of CNM. There were 226 patients (46%) with CLT and 220 (44%) with CNM. Patients with CLT were more often female (88% vs. 71%; P CLT was associated with a 39% decreased odds of CNM after adjusting for age, gender, tumor size, PTC histopathologic subtype, and presence of lymphovascular invasion (odds ratio, 0.61; 95% confidence interval, 0.38-0.99; P = .046). Predicted probability modeling showed that all females with CLT and no suspicious nodal findings on ultrasonography had a 9-11% risk of CNM with pT1a tumors. Female patients of all ages with CLT and small PTCs have the least incidence of CNM. Copyright © 2013 Mosby, Inc. All rights reserved.

  16. Effects of chronic furosemide on central neural hyperactivity and cochlear thresholds after cochlear trauma in guinea pig

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    Wilhelmina eMulders

    2014-08-01

    Full Text Available Increased neuronal spontaneous firing rates have been observed throughout the central auditory system after trauma to the cochlea and this hyperactivity is believed to be associated with the phantom perception of tinnitus. Previously we have shown in an animal model of hearing loss, that an acute injection with furosemide can significantly decrease hyperactivity after cochlear trauma and eliminate behavioural evidence of tinnitus of early onset. However, furosemide also has the potential to affect cochlear thresholds. In this paper we measured the effects of a chronic (daily injections for 7 days furosemide treatment on the spontaneous firing rate of inferior colliculus neurons and on cochlear thresholds in order to establish whether a beneficial effect on hyperactivity can be obtained without causing additional hearing loss. Guinea pigs were exposed to a 10 kHz, 124dB, 2 hour acoustic trauma, and after 5 days of recovery, were given daily i.p. injections of 80mg/kg furosemide or an equivalent amount of saline. The activity of single IC neurons was recorded 24 hours following the last injection. The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus. These results that suggest a long term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.

  17. Mutation Status and Immunoglobulin Gene Rearrangements in Patients from Northwest and Central Region of Spain with Chronic Lymphocytic Leukemia

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    I. González-Gascón y Marín

    2014-01-01

    Full Text Available The aim of this study was to investigate the frequency and mutation status of the immunoglobulin heavy variable chain (IGHV in a cohort of 224 patients from northwest and central region of Spain diagnosed with chronic lymphocytic leukemia (CLL, and to correlate it with cytogenetic abnormalities, overall survival (OS and time to first treatment (TTFT. 125 patients had mutated IGHV, while 99 had unmutated IGHV. The most frequently used IGHV family was IGHV3, followed by IGHV1 and IGHV4. The regions IGHV3-30, IGHV1-69, IGHV3-23, and IGHV4-34 were the most commonly used. Only 3.1% of the patients belonged to the subfamily IGHV3-21 and we failed to demonstrate a worse clinical outcome in this subgroup. The IGHV4 family appeared more frequently with mutated pattern, similar to IGHV3-23 and IGHV3-74. By contrast, IGHV1-69 was expressed at a higher frequency in unmutated CLL patients. All the cases from IGHV3-11 and almost all from IGHV5-51 subfamily belonged to the group of unmutated CLL.

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

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

    2012-01-01

    The implementation of new diagnostic and therapeutic technologies is related to expanding financial needs. The escalation of expenses for health protection and simultaneous economic problems has resulted in an interest in the subject of economic assessment. Decision makers in the health sector should have reasonable tools that will allow them to make complex evaluations of the economic suitability of health technologies. Economic analysis should also prove that launching new procedures can save money. Numerous studies indicate that chronic pain and psycho-sociological variables lead to a worse quality of life. Chronic pain issues are a major public health problem, by virtue of the difficulties in efficient therapy and the social costs reflected in incapability of work and disability. Spinal cord stimulation is the most efficacious procedure in the treatment of chronic pain. The aim of the study was to estimate the costs of treatment of 37 patients suffering from refractory angina pectoris and neuropathic pain who underwent SCS surgery between 2002 and 2008 in the Neurosurgery Clinic of the 10th Military Hospital in Bydgoszcz in the period of two years before and two years after spinal cord stimulation. The authors also assessed quality of life, using the SF 36 questionnaire, and degree of pain using VAS. The issue was examined with a cost-benefit analysis. Cost was understood as the expenses made two years before and two years after the SCS procedure. The benefits were health care expenses saved by implementation of the SCS procedure. All the costs included in both alternative treatment techniques in a period of 5 years underwent a discounting procedure. The authors also included the price of the neurostimulator under a sensitivity analysis. To assess the quality of life before and after the SCS procedure, a SF 36 questionnaire was used, and to assess the level of pain before and after the SCS procedure, the VAS scale. The costs of treatment of refractory angina

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

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    Domenico Intiso

    2015-06-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Jensen, Troels Staehelin

    2006-01-01

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

  2. 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. 

  3. Diabetes-induced microvascular complications at the level of the spinal cord; a contributing factor in diabetic neuropathic pain.

    Science.gov (United States)

    Ved, N; Da Vitoria Lobo, M E; Bestall, S M; L Vidueira, C; Beazley-Long, N; Ballmer-Hofer, K; Hirashima, M; Bates, D O; Donaldson, L F; Hulse, R P

    2018-05-17

    Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord and regulation of nociception has not been investigated despite neuropathic pain being common in diabetes. We hypothesised that hyperglycaemia-induced endothelial degeneration in the spinal cord, due to suppression of VEGF-A/VEGFR2 signalling, induces diabetic neuropathic pain. Nociceptive pain behaviour was investigated in a chemically induced model of type 1 diabetes (streptozotocin induced, insulin supplemented; either vehicle or VEGF-A 165 b treated) and an inducible endothelial knockdown of VEGFR2 (tamoxifen induced). Diabetic animals developed mechanical allodynia and heat hyperalgesia. This was associated with a reduction in the number of blood vessels and reduction in Evans blue extravasation in the lumbar spinal cord of diabetic animals versus age-matched controls. Endothelial markers occludin, CD31 and VE-cadherin were downregulated in the spinal cord of the diabetic group versus controls, as well as a concurrent reduction of VEGF-A 165 b expression. In diabetic animals, VEGF-A 165 b treatment (biweekly intraperitoneal, 20 ng g -1 ) restored normal Evans blue extravasation and prevented vascular degeneration, diabetes-induced central neuron activation and neuropathic pain. Inducible knockdown of VEGFR2 (tamoxifen treated Tie2CreER T2 -vegfr2 flfl mice) led to a reduction in blood vessel network volume in the lumbar spinal cord and development of heat hyperalgesia. These findings indicate that hyperglycaemia leads to a reduction in the VEGF-A/VEGFR2 signalling cascade resulting in endothelial dysfunction in the spinal cord, which could be an undiscovered contributing factor to diabetic neuropathic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All

  4. A Single Sub-anesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats

    Science.gov (United States)

    Wang, Jing; Goffer, Yossef; Xu, Duo; Tukey, David S.; Shamir, D. B.; Eberle, Sarah E.; Zou, Anthony H.; Blanck, Thomas J.J.; Ziff, Edward B.

    2011-01-01

    Background Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its anti-nociceptive properties. Methods We examined whether the spared nerve injury (SNI) model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats SNI-induced depression. Results SNI-treated rats, compared with control, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10mg/kg) did not alter SNI-induced hypersensitivity; however, it treated SNI-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control 5 days after administration). Conclusions Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain. PMID:21934410

  5. Perspectives on physiotherapy guidelines for chronic low back pain

    Directory of Open Access Journals (Sweden)

    P. Berger

    2007-01-01

    disability. The modalities used in conjunction with active exercises include thermal, massage, electrical stimulation, traction, transcutaneous electrical nerve stimulation (Tens, myofascial release, dry needling, mobilization and acupuncture. An algorithm is provided with the intention of developing protocols for breaking the pain cycle in both nociceptive and neuropathic pain states and in reducing inflammation which is a component of both peripheral and central sensitization. Pain rehabilitation is a useful and cost-effective approach to chronic pain management and makes patients’ responsible partners in their own progress. It encourages planning, pacing of activities and activity related goal setting into a clear and goal-oriented context that provides the patient with control and improved quality of life.

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

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    Schaefer C

    2014-10-01

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

  7. In vivo evaluation of the hippocampal glutamate, GABA and the BDNF levels associated with spatial memory performance in a rodent model of neuropathic pain.

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    Saffarpour, S; Shaabani, M; Naghdi, N; Farahmandfar, M; Janzadeh, A; Nasirinezhad, F

    2017-06-01

    Patients with chronic pain usually suffer from learning and memory impairment which may significantly decrease their quality of life. Despite laboratory and clinical studies, the mechanism underlying this memory impairment remains elusive. We evaluated the effect of chronic pain on the glutamate and GABA levels and BDNF expression in the CA1 region of hippocampus as a possible explanation for memory impairment related to neuropathic pain. In this respect, 30 male rats were randomly allocated to 3 groups as control, sham and neuropathic. Neuropathic pain was induced by a chronic constriction injury of the sciatic nerve (CCI) and mechanical allodynia and the spatial memory was assessed using the Von Frey filaments and Morris water maze respectively. To determine the potential mechanisms, the in vivo extracellular levels of glutamate and γ-aminobutyric acid (GABA) were measured by microdialysis and the brain-derived neurotrophic factor (BDNF) expression was determined by using western blots technique in the hippocampus on days 14 and 21 post-CCI. We showed that CCI impaired spatial learning and memory in Morris water maze (MWM) task. BDNF expression level and glutamate concentration significantly decreased in rats with chronic constriction injury of the sciatic nerve (PGABA increased in hippocampal CA1 region (PGABA concentration and decrease in the glutamate and BDNF levels in the CA1 region of the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.

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    Patel, Ryan; Dickenson, Anthony H

    2016-07-01

    Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.

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

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

    2018-07-04

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

  10. Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

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    Sagen J

    2016-06-01

    tail of mice significantly increased tail withdrawal latencies in the tail flick test, demonstrating that both local anesthetics attenuate responding to a brief noxious stimulus.Conclusion: These findings showed that mepivacaine, rather than lidocaine, consistently attenuated two distinct symptoms of neuropathic pain and suggest that topical formulations of this local anesthetic could have utility in the alleviation of clinical HIV neuropathic pain. Keywords: chronic pain, acute pain, analgesia, AIDs-related pain, distal sensory neuropathy, local anesthetics

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

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

    2010-01-01

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

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

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    Simona Mirel

    2017-02-01

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

  13. The management of neuropathic ulcers of the foot in diabetes by shock wave therapy

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    Pascone Michele

    2009-05-01

    Full Text Available Abstract Background Diabetes is becoming one of the most common chronic diseases, and ulcers are its most serious complication. Beginning with neuropathy, the subsequent foot wounds frequently lead to lower extremity amputation, even in the absence of critical limb ischemia. In recent years, some researchers have studied external shock wave therapy (ESWT as a new approach to soft tissue wound healing. The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers. Methods We designed a randomized, prospective, controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies. One group was treated with standard care and shock wave therapy. The other group was treated with only standard care. The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization. Results After 20 weeks of treatment, 53.33% of the ESWT-treated patients had complete wound closure compared with 33.33% of the control patients, and the healing times were 60.8 and 82.2 days, respectively (p 2/die in the ESWT-group and 1.30 mm2/die in the control group (p Conclusion Therefore, ESWT may be a useful adjunct in the management of diabetic foot ulceration. Trial registration Current Controlled Trials ISRCTN21800909

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

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

    2017-10-02

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

  15. Fear of pain in children and adolescents with neuropathic pain and CRPS

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    Simons, Laura E.

    2015-01-01

    A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Due to faulty nerve signaling, individuals with neuropathic pain and CRPS may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to down-regulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, while high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear as well as evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with CRPS suggest breakthroughs in our ability to ameliorate these issues. PMID:26785161

  16. Fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome.

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    Simons, Laura E

    2016-02-01

    A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Because of faulty nerve signaling, individuals with neuropathic pain and complex regional pain syndrome may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to downregulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, whereas high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear and evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with complex regional pain syndrome suggest breakthroughs in our ability to ameliorate these issues.

  17. Alterations in the Anandamide Metabolism in the Development of Neuropathic Pain

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    Natalia Malek

    2014-01-01

    Full Text Available Endocannabinoids (EC, particularly anandamide (AEA, released constitutively in pain pathways might be accountable for the inhibitory effect on nociceptors. Pathogenesis of neuropathic pain may reflect complex remodeling of the dorsal root ganglia (DRGs and spinal cord EC system. Multiple pathways involved both in the biosynthesis and degradation of AEA have been suggested. We investigated the local synthesis and degradation features of AEA in DRGs and spinal cord during the development and maintenance of pain in a model of chronic constriction injury (CCI. All AEA synthesis and degradation enzymes are present on the mRNA level in DRGs and lumbar spinal cord of intact as well as CCI-treated animals. Deregulation of EC system components was consistent with development of pain phenotype at days 3, 7, and 14 after CCI. The expression levels of enzymes involved in AEA degradation was significantly upregulated ipsilateral in DRGs and spinal cord at different time points. Expression of enzymes of the alternative, sPLA2-dependent and PLC-dependent, AEA synthesis pathways was elevated in both of the analyzed structures at all time points. Our data have shown an alteration of alternative AEA synthesis and degradation pathways, which might contribute to the variation of AEA levels and neuropathic pain development.

  18. Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

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    Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

    2018-05-31

    Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. In contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared to sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.

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

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    Katarzyna Popiolek-Barczyk

    2014-01-01

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

  20. The refined biomimetic NeuroDigm GEL™ model of neuropathic pain in a mature rat [version 2; referees: 1 approved, 2 approved with reservations

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    Mary R. Hannaman

    2017-05-01

    Full Text Available Background: Many humans suffering with chronic neuropathic pain have no objective evidence of an etiological lesion or disease. Frequently their persistent pain occurs after the healing of a soft tissue injury. Based on clinical observations over time, our hypothesis was that after an injury in mammals the process of tissue repair could cause chronic neural pain. Our objectives were to create the delayed onset of neuropathic pain in rats with minimal nerve trauma using a physiologic hydrogel, and characterize the rats’ responses to known analgesics and a targeted biologic.   Methods: In mature male Sprague Dawley rats (age 9.5 months a percutaneous implant of tissue-derived hydrogel was placed in the musculofascial tunnel of the distal tibial nerve. Subcutaneous morphine (3 mg/kg, celecoxib (10 mg/kg, gabapentin (25 mg/kg and duloxetine (10 mg/kg were each screened in the model three times each over 5 months after pain behaviors developed. Sham and control groups were used in all screenings. A pilot study followed in which recombinant human erythropoietin (200 units was injected by the GEL™ neural procedure site.   Results: The GEL group gradually developed mechanical hypersensitivity lasting months. Morphine, initially effective, had less analgesia over time. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses demonstrated profound analgesia at all times tested. The injected erythropoietin markedly decreased bilateral pain behavior that had been present for over 4 months, p ≤ 0.001. Histology of the GEL group tibial nerve revealed a site of focal neural remodeling, with neural regeneration, as found in nerve biopsies of patients with neuropathic pain.   Conclusion: The refined NeuroDigm GEL™ model induces a neural response resulting in robust neuropathic pain behavior. The analgesic responses in this model reflect known responses of humans with neuropathic pain. The targeted recombinant human erythropoietin

  1. Analyzing implementation dynamics using theory-driven evaluation principles: lessons learnt from a South African centralized chronic dispensing model.

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    Magadzire, Bvudzai Priscilla; Marchal, Bruno; Mathys, Tania; Laing, Richard O; Ward, Kim

    2017-12-04

    Centralized dispensing of essential medicines is one of South Africa's strategies to address the shortage of pharmacists, reduce patients' waiting times and reduce over-crowding at public sector healthcare facilities. This article reports findings of an evaluation of the Chronic Dispensing Unit (CDU) in one province. The objectives of this process evaluation were to: (1) compare what was planned versus the actual implementation and (2) establish the causal elements and contextual factors influencing implementation. This qualitative study employed key informant interviews with the intervention's implementers (clinicians, managers and the service provider) [N = 40], and a review of policy and program documents. Data were thematically analyzed by identifying the main influences shaping the implementation process. Theory-driven evaluation principles were applied as a theoretical framework to explain implementation dynamics. The overall participants' response about the CDU was positive and the majority of informants concurred that the establishment of the CDU to dispense large volumes of medicines is a beneficial strategy to address healthcare barriers because mechanical functions are automated and distribution of medicines much quicker. However, implementation was influenced by the context and discrepancies between planned activities and actual implementation were noted. Procurement inefficiencies at central level caused medicine stock-outs and affected CDU activities. At the frontline, actors were aware of the CDU's implementation guidelines regarding patient selection, prescription validity and management of non-collected medicines but these were adapted to accommodate practical realities and to meet performance targets attached to the intervention. Implementation success was a result of a combination of 'hardware' (e.g. training, policies, implementation support and appropriate infrastructure) and 'software' (e.g. ownership, cooperation between healthcare

  2. Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex.

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    Maral Tajerian

    Full Text Available Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC, and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with abnormal behavior and pathological gene expression in the central nervous system. DNA methylation might also be involved in mediating the pathologies associated with chronic pain in the brain. We therefore tested a whether alterations in DNA methylation are found in the brain long after chronic neuropathic pain is induced in the periphery using the spared nerve injury modal and b whether these injury-associated changes are reversible by interventions that reverse the pathologies associated with chronic pain. Six months following peripheral nerve injury, abnormal sensory thresholds and increased anxiety were accompanied by decreased global methylation in the PFC and the amygdala but not in the visual cortex or the thalamus. Environmental enrichment attenuated nerve injury-induced hypersensitivity and reversed the changes in global PFC methylation. Furthermore, global PFC methylation correlated with mechanical and thermal sensitivity in neuropathic mice. In summary, induction of chronic pain by peripheral nerve injury is associated with epigenetic changes in the brain. These changes are detected long after the original injury, at a long distance from the site of injury and are reversible with environmental manipulation. Changes in brain structure and

  3. Select tissue mineral concentrations and chronic wasting disease status in mule deer from North-central Colorado.

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    Wolfe, Lisa L; Conner, Mary M; Bedwell, Cathy L; Lukacs, Paul M; Miller, Michael W

    2010-07-01

    Trace mineral imbalances have been suggested as having a causative or contributory role in chronic wasting disease (CWD), a prion disease of several North American cervid species. To begin exploring relationships between tissue mineral concentrations and CWD in natural systems, we measured liver tissue concentrations of copper, manganese, and molybdenum in samples from 447 apparently healthy, adult (> or = 2 yr old) mule deer (Odocoileus hemionus) culled or vehicle killed from free-ranging populations in north-central Colorado, United States, where CWD occurs naturally; we also measured copper concentrations in brain-stem (medulla oblongata at the obex) tissue from 181 of these deer. Analyses revealed a wide range of concentrations of all three minerals among sampled deer (copper: 5.6-331 ppm in liver, 1.5-31.9 ppm in obex; manganese: 0.1-21.4 ppm in liver; molybdenum: 0.5-4.0 ppm in liver). Bayesian multiple regression analysis revealed a negative association between obex copper (-0.097; 95% credible interval -0.192 to -0.006) and the probability of sampled deer also being infected with CWD, as well as a positive association between liver manganese (0.158; 95% credible interval 0.066 to 0.253) and probability of infection. We could not discern whether the tendencies toward lower brain-stem copper concentrations or higher systemic manganese concentrations in infected deer preceded prion infection or rather were the result of infection and its subsequent effects, although the distribution of trace mineral concentrations in infected deer seemed more suggestive of the latter.

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

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

    2014-01-01

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

  5. Intervertebral Foramen Injection of Ozone Relieves Mechanical Allodynia and Enhances Analgesic Effect of Gabapentin in Animal Model of Neuropathic Pain.

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    Luo, Wen-Jun; Yang, Fan; Yang, Fei; Sun, Wei; Zheng, Wei; Wang, Xiao-Liang; Wu, Fang-Fang; Wang, Jiang-Lin; Wang, Jia-Shuang; Guan, Su-Min; Chen, Jun

    2017-07-01

    In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. Experimental trial in rats. Institute for Biomedical Sciences of Pain. By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (bee venom, complete Freud's adjuvant.

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

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

    2016-11-01

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

  7. Cognitive Performance Is Related to Central Sensitization and Health-related Quality of Life in Patients with Chronic Whiplash-Associated Disorders and Fibromyalgia.

    Science.gov (United States)

    Coppieters, Iris; Ickmans, Kelly; Cagnie, Barbara; Nijs, Jo; De Pauw, Robby; Noten, Suzie; Meeus, Mira

    2015-01-01

    A growing body of research has demonstrated that impaired central pain modulation or central sensitization (CS) is a crucial mechanism for the development of persistent pain in chronic whiplash-associated disorders (WAD) and fibromyalgia (FM) patients. Furthermore, there is increasing evidence for cognitive dysfunctions among these patients. In addition, chronic WAD and FM patients often report problems with health-related quality of life (QoL). Yet, there is limited research concerning the interrelations between cognitive performance, indices of CS, and health-related QoL in these patients. (1) Examining the presence of cognitive impairment, CS, and limitations on health-related QoL in patients with chronic WAD and FM compared to healthy controls. (2) Examining interrelations between performance-based cognitive functioning, CS, and self-reported health-related QoL in these 3 study groups. A case-control study was conducted. The present study took place at the University Hospital Brussels, the University of Brussels, and the University of Antwerp. Fifty-nine patients (16 chronic WAD patients, 21 FM patients, and 22 pain-free volunteers) filled out the Short Form 36 item Health Survey (SF-36), a self-reported psychosocial questionnaire, to assess health-related QoL. Next, they were subjected to various pain measurements (pressure hyperalgesia, deep-tissue hyperalgesia, temporal summation [TS], and conditioned pain modulation [CPM]). Finally, participants completed a battery of performance-based cognitive tests (Stroop task, psychomotor vigilance task [PVT], and operation span task [OSPAN]). Significant cognitive impairment, bottom-up sensitization, and decreased health-related QoL were demonstrated in patients with chronic WAD and FM compared to healthy controls (P fibromyalgia, whiplash, central sensitization, conditioned pain modulation, temporal summation, cognition, quality of life.

  8. Newer N-phthaloyl GABA derivatives with antiallodynic and antihyperalgesic activities in both sciatic nerve and spinal nerve ligation models of neuropathic pain.

    Science.gov (United States)

    Yogeeswari, Perumal; Ragavendran, Jegadeesan Vaigunda; Sriram, Dharmarajan; Kavya, Ramkumar; Vanitha, Kaliappan; Neelakantan, Harshini

    2008-01-01

    There is considerable research evidence supporting a palliative role for gamma-aminobutyric acid (GABA)-ergic neurotransmission and voltage-gated sodium channel blockade in neuropathic pain conditions. Hence, the present study was undertaken to assess the peripheral analgesic, antiallodynic and antihyperalgesic activities of the synthesized structural analogues of GABA. The screening study included acute tissue injury, chronic constriction injury (CCI), and spinal nerve ligation (SNL) models of neuropathic pain. All of the tested compounds sup-pressed the acetic acid-induced writhing response significantly in comparison to the control. In particular, compound JVP-8 was observed to be the most active compound with percent inhibition greater than that of the standard drug aspirin (97.8% inhibition of writhing response as against 97.0% shown by aspirin). In neuropathic pain studies, compound JVP-5 (100 mg/kg i.p.) emerged as the most active compound affording maximum protection against dynamic allodynia and mechanical hyperalgesia in the CCI model, and against spontaneous pain and mechanical hyperalgesia in SNL rats. In this study, we have demonstrated that combining phthalimide pharmacophore with GABA has evolved compounds effective for the treatment of neuropathic pain. (c) 2008 S. Karger AG, Basel.

  9. Lack of Analgesic Synergy of the Cholecystokinin Receptor Antagonist Proglumide and Spinal Cord Stimulation for the Treatment of Neuropathic Pain in Rats.

    Science.gov (United States)

    Inoue, Shinsuke; Johanek, Lisa M; Sluka, Kathleen A

    2017-08-01

    Neuropathic pain is difficult to manage and treat. Spinal cord stimulation (SCS) has become an established procedure for treating chronic neuropathic pain that is refractory to pharmacological therapy. In order to achieve better analgesia, a number of studies have evaluated the effectiveness of combining drug therapy with SCS. Cholecystokinin antagonists, such as proglumide, enhance the analgesic efficacy of endogenous opioids in animal models of pain. We previously reported that both systemic and spinal administration of proglumide enhances analgesia produced by both low- and high-frequency transcutaneous electrical nerve stimulation (TENS). Since SCS produces analgesia through endogenous opioids, we hypothesized that the analgesic effect of SCS would be enhanced through co-administration with proglumide in animals with neuropathic pain. Male Sprague-Dawley rats (n = 40) with spared nerve injury were given proglumide (20 mg/kg, i.p.) or saline prior to treatment with SCS (sham, 4 Hz, and 60 Hz). Mechanical withdrawal thresholds of the paw were measured before and after induction of nerve injury, and after SCS. Physical activity levels were measured after SCS. Both proglumide and SCS when given independently significantly increased withdrawal thresholds two weeks after nerve injury. However, there was no additional effect of combining proglumide and SCS on mechanical withdrawal thresholds or activity levels in animals with nerve injury. Proglumide may be a candidate for achieving analgesia for patients with refractory neuropathic pain conditions, but does not enhance analgesia produced by SCS. © 2017 International Neuromodulation Society.

  10. Effects of electroacupuncture on orphanin FQ immunoreactivity and preproorphanin FQ mRNA in nucleus of raphe magnus in the neuropathic pain rats.

    Science.gov (United States)

    Ma, Fei; Xie, Hong; Dong, Zhi-Qiang; Wang, Yan-Qing; Wu, Gen-Cheng

    2004-07-15

    Orphanin FQ (OFQ) is an endogenous ligand for opioid receptor-like-1 (ORL1) receptor. Previous studies have shown that both OFQ immunoreactivity and preproorphanin FQ (ppOFQ) mRNA expression could be observed in the brain regions involved in pain modulation, e.g., nucleus of raphe magnus (NRM), dorsal raphe nucleus (DRN), and ventrolateral periaqueductal gray (vlPAG). It was reported that electroacupuncture (EA) has analgesic effect on neuropathic pain, and the analgesic effect was mediated by the endogenous opioid peptides. In the present study, we investigated the effects of EA on the changes of OFQ in the neuropathic pain rats. In the sciatic nerve chronic constriction injury (CCI) model, we investigated the changes of ppOFQ mRNA and OFQ immunoreactivity in NRM after EA by in situ hybridization (ISH) and immunohistochemistry methods, respectively. Then, the ppOFQ mRNA-positive and OFQ immunoreactive cells were counted under a computerized image analysis system. The results showed that expression of ppOFQ mRNA decreased and OFQ immunoreactivity increased after EA treatment in the neuropathic pain rats. These results indicated that EA modulated OFQ synthesis and OFQ peptide level in NRM of the neuropathic pain rats. Copyright 2004 Elsevier Inc.

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

    Science.gov (United States)

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

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

  12. Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain.

    Science.gov (United States)

    Sawynok, Jana; Zinger, Celia

    2016-01-01

    Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option. This report summarizes both published and unpublished results of clinical trials with AmiKet. In post-herpetic neuralgia (PHN), AmiKet produces a significant analgesia which is comparable to that produced by oral gabapentin. In diabetic painful neuropathy, AmiKet showed a strong trend towards pain reduction. In mixed neuropathic pain, case series reports suggest a favourable response rate, but are limited by trial characteristics. AmiKet is absorbed minimally following topical administration. Over 700 patients have now received topical AmiKet in clinical regimens, and it is well-tolerated with the adverse effects mainly being application site reactions. Both agents are polymodal, and several mechanisms may contribute to the peripheral efficacy of AmiKet. Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination.

  13. A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

    2016-01-01

    The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

  14. 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.

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

    Science.gov (United States)

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

    2016-09-01

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

  16. Occupational therapy for patients with chronic diseases: CVA, rheumatoid arthritis and progressive diseases of the central nervous system.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1997-01-01

    A substantial proportion of the patients treated by occupational therapists have a chronic disease. The aim of this study was to describe the outlines of occupational therapy treatment for three specific groups of chronic diseases: progressive neurological diseases, cerebrovascular accident and

  17. Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

    Directory of Open Access Journals (Sweden)

    Schmitz Beate

    2008-08-01

    Full Text Available Abstract Background Ample evidence suggests a substantial contribution of cellular and molecular changes in the spinal cord to the induction and persistence of chronic neuropathic pain conditions. While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology. In the present study we focused on two cathepsins, CATS and CATX, and studied their spatiotemporal expression and activity during the development and progression of neuropathic pain in the CNS of the rat 5th lumbar spinal nerve transection model (L5T. Results Immediately after the lesion, both cathepsins, CATS and CATX, were upregulated in the spinal cord. Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T. The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain. The cellular distribution of CATS and CATX was, however, considerably different. Conclusion The cellular distribution and the spatio-temporal development of the altered expression of CATS and CATX suggest that these proteins are important players in the spinal mechanisms involved in chronic pain induction and maintenance.

  18. Chronic pain: the burden of disease and treatment innovations

    Directory of Open Access Journals (Sweden)

    S. Monti

    2015-10-01

    Full Text Available Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Effi cacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients’ long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR and noradrenaline reuptake inhibition (NRI, introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profi le, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic fi eld, particularly in the treatment of osteoarthritis and low back pain.

  19. The Rare Painful Phenomena - Chronic Paroxysmal Hemicrania-tic Syndrome as a Clinically Isolated Syndrome of the Central Nervous System.

    Science.gov (United States)

    Ljubisavljevic, Srdjan; Prazic, Ana; Lazarevic, Miodrag; Stojanov, Dragan; Savic, Dejan; Vojinovic, Slobadan

    2017-02-01

    The association of paroxysmal hemicrania with trigeminal neuralgia (TN) has been described and called paroxysmal hemicrania-tic syndrome (PH-tic). We report the case of a patient diagnosed as having chronic PH-tic (CPH-tic) syndrome as a clinically isolated syndrome of the central nervous system (CNS) (CIS).A forty year old woman was admitted to our hospital suffering from right facial pain for the last 2 years. The attacks were paroxysmal, neuralgiform, consisting of throb-like sensations, which developed spontaneously or were triggered by different stimuli in right facial (maxilar and mandibular) areas. Parallel with those, she felt a throbbing orbital and frontal pain with homolateral autonomic symptoms such as conjunctival injection, lacrimation, and the feeling that the ear on the same side was full. This pain lasted most often between 15 and 20 minutes. Beyond hemifacial hypoesthesia in the region of right maxilar and mandibular nerve, the other neurological finding was normal. Magnetic resonance imaging (MRI) study showed a T2-weighted multiple hyperintense paraventricular lesion and hyperintense lesion in the right trigeminal main sensory nucleus and root inlet, all of them being hypointense on T1-weighted image. All of these lesions were hypointense in gadolinium-enhanced T1-weighted images. Neurophysiological studies of trigeminal nerve (somatosensory evoked potentials and blink reflex) correlated with MRI described lesions. The patient's pain bouts were improved immediately after treatment with indomethacin, and were completely relieved with lamotrigine for a longer period. According to the actual McDonald's criteria, clinical state was defined as CIS which was clinically presented by CPH-tic syndrome.Even though it is a clinical rarity and its etiology is usually idiopathic, CPH-tic syndrome can also be symptomatic. When dealing with symptomatic cases, like the one described here, when causal therapy is not possible due to the nature of the primary

  20. Risk Factors for Chronic Diseases and Multimorbidity in a Primary Care Context of Central Argentina: A Web-Based Interactive and Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    David E. V. Olivares

    2017-03-01

    Full Text Available Global health agencies estimate an increase of chronic diseases in South America. Nevertheless, few studies have investigated chronic diseases and their risk factors in the perspective of multimorbidity. This research aimed to identify these aspects in a primary health care setting of central Argentina. The Pan America version of the STEP wise approach surveillance (STEPS instrument of the World Health Organization was applied to 1044 participants, 365 men and 679 women, with a mean age of 43 years. High prevalence of overweight (33.5%, obesity (35.2%, central obesity (54%, dyslipidemia (43.5%, metabolic syndrome (21.1%, low intake of fruit and vegetables (91.8%, low levels of physical activity (71.5%, risky alcohol consumption (28%, and smoking (22.5% were detected. Hypertension and diabetes were the most prevalent chronic conditions and the total prevalence of multimorbidity was 33.1%, with 2, 3, 4, 5 and 6 chronic conditions found in 19.9%, 9.1%, 2.6%, 1.1% and 0.4% of the population, respectively. Multimorbidity affected 6.4% of the young, 31.7% of the adults, and 60.6% of the elderly, and was more prevalent among women, and in participants with lower levels of education. Having multimorbidity was significantly associated with obesity, central obesity, and higher concentrations of total blood cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose. A website was made available to the participants in order to share the experimental results and health-promoting information.

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

    Science.gov (United States)

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

    2016-04-08

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

  2. Epidemiology of chronic kidney disease, with special emphasis on chronic kidney disease of uncertain etiology, in the north central region of Sri Lanka.

    Science.gov (United States)

    Jayasekara, Kithsiri Bandara; Dissanayake, Dhammika Menike; Sivakanesan, Ramiah; Ranasinghe, Asanga; Karunarathna, Ranawaka Hewage; Priyantha Kumara, Gardiye Waligamage Gamini

    2015-01-01

    The aim of the study was to identify the epidemiology of chronic kidney disease of uncertain etiology in Sri Lanka. A cross-sectional study was carried out by analyzing health statistics, and three cohort studies were conducted (n = 15 630, 3996, and 2809) to analyze the demographic information, age-specific prevalence, etiology, and stage of presentation. We screened 7604 individuals for chronic kidney disease of uncertain etiology. The results showed that the male:female ratio was 2.4:1, the mean age of patients was 54.7 ± 8 years, 92% of the patients were farmers, and 93% consumed water from shallow dug wells. Familial occurrence was common (36%). The prevalence of chronic kidney disease in different age groups was 3% in those aged 30-40 years; 7% in those aged 41-50 years, 20% in those aged 51-60 years, and 29% in those older than 60 years. Chronic kidney disease of uncertain etiology was diagnosed in 70.2% of patients, while 15.7% and 9.6% were due to hypertension and diabetic mellitus, respectively. The majority of patients were stage 4 (40%) at first presentation, while 31.8% were stage 3 and 24.5% were stage 5. Stage 1 and 2 presentation accounted for only 3.4%. Low prevalence of CKDU was noticed (1.5%) among those who consumed water from natural springs. Prevalence was highest among males, rice farming communities, and those presenting at later disease stages.

  3. Epidural spinal cord stimulation for neuropathic pain: a neurosurgical multicentric Italian data collection and analysis.

    Science.gov (United States)

    Colombo, Elena Virginia; Mandelli, Carlo; Mortini, Pietro; Messina, Giuseppe; De Marco, Nicola; Donati, Roberto; Irace, Claudio; Landi, Andrea; Lavano, Angelo; Mearini, Massimo; Podetta, Stefano; Servello, Domenico; Zekaj, Edvin; Valtulina, Carlo; Dones, Ivano

    2015-04-01

    Spinal cord stimulation (SCS) is a technique used worldwide to treat several types of chronic neuropathic pain refractory to any conservative treatment. The aim of this data collection is to enforce evidence of SCS effectiveness on neuropathic chronic pain reported in the literature and to speculate on the usefulness of the trial period in determining the long-term efficacy. Moreover, the very low percentage of undesired side effects and complications reported in our case series suggests that all implants should be performed by similarly well-trained and experienced professionals. A multicentric data collection on a common database from 11 Italian neurosurgical departments started 3 years ago. Two different types of electrodes (paddle or percutaneous leads) were used. Of 122 patients, 73 % (N = 89) were submitted to a trial period, while the remaining patients underwent the immediate permanent implant (N = 33). Statistical comparisons of continuous variables between groups were performed. Most of the patients (80 %) had predominant pain to their lower limbs, while only 17 % of patients had prevalent axial pain. Significant reduction in pain, as measured by variation in visual analogue scale (VAS) score, was observed at least 1 year after implantation in 63.8 % of the cases, 59.5 % of patients who underwent a test trial and 71.4 % of patients who underwent permanent implant at once. No statistical differences were found between the lower-limb pain group and the axial pain group. No relevant differences in long-term outcomes were observed in previously tested patients compared with patients implanted at once. Through this analysis we hope to recruit new centres, to give more scientific value to our results.

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

    Science.gov (United States)

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

    2016-08-25

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

  5. The β-lactam clavulanic acid mediates glutamate transport-sensitive pain relief in a rat model of neuropathic pain

    DEFF Research Database (Denmark)

    Kristensen, P J; Gegelashvili, G; Munro, G

    2017-01-01

    -regulates glutamate transporters both in vitro and in vivo. Crucially, a similar up-regulation of glutamate transporters in human spinal astrocytes by clavulanic acid supports the development of novel β-lactam-based analgesics, devoid of antibacterial activity, for the clinical treatment of chronic pain.......BACKGROUND: Following nerve injury, down-regulation of astroglial glutamate transporters (GluTs) with subsequent extracellular glutamate accumulation is a key factor contributing to hyperexcitability within the spinal dorsal horn. Some β-lactam antibiotics can up-regulate GluTs, one of which......, ceftriaxone, displays analgesic effects in rodent chronic pain models. METHODS: Here, the antinociceptive actions of another β-lactam clavulanic acid, which possesses negligible antibiotic activity, were compared with ceftriaxone in rats with chronic constriction injury (CCI)-induced neuropathic pain...

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

    Science.gov (United States)

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

    2017-09-08

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

  7. Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: A pilot study.

    Science.gov (United States)

    Choi, Gyu-Sik; Kwak, Sang Gyu; Lee, Han Do; Chang, Min Cheol

    2018-02-28

    Central pain can occur following traumatic brain injury, leading to poor functional recovery, limitation of activities of daily living, and decreased quality of life. The aim of this study was to determine whether high-frequency (10 Hz) repetitive transcranial magnetic stimulation, applied over the primary motor cortex of the affected hemisphere, can be used to manage chronic central pain after mild traumatic brain injury. Prospective randomized feasibility study. Twelve patients with mild traumatic brain injury and chronic central pain were randomly assigned to transcranial magnetic stimulation (high-frequency stimulation, 10 sessions) or sham groups. Diffuse tensor tractography revealed partially injured spinothalamocortical tracts in all recruited patients. A numerical rating scale (NRS) was used to evaluate pain intensity during pre-treatment and immediately after the 5th transcranial magnetic stimulation session (post1), 10th transcranial magnetic stimulation session (post2), and 1 (post3), 2 (post4), and 4 weeks (post 5) after finishing treatment. Physical and mental health status were evaluated using the Short Form 36 Health Survey (SF-36), including physical and mental component scores (PCS, MCS). The NRS score of the repetitive transcranial magnetic stimulation group was significantly lower than the sham group score at all clinical evaluation time-points during and after transcranial magnetic stimulation sessions. The transcranial magnetic stimulation group's SF-36 PCS score was significantly higher at post2, post3, post4, and post5 compared with the sham group. High-frequency transcranial magnetic stimulation may be used to manage chronic central pain and improve quality of life in patients with mild traumatic brain injury. However, this is a pilot study and further research is needed.

  8. Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: A pilot study

    Directory of Open Access Journals (Sweden)

    Gyu-sik Choi

    2018-01-01

    Full Text Available Objective: Central pain can occur following traumatic brain injury, leading to poor functional recovery, limitation of activities of daily living, and decreased quality of life. The aim of this study was to determine whether high-frequency (10 Hz repetitive transcranial magnetic stimulation, applied over the primary motor cortex of the affected hemisphere, can be used to manage chronic central pain after mild traumatic brain injury. Design: Prospective randomized feasibility study. Methods: Twelve patients with mild traumatic brain injury and chronic central pain were randomly assigned to transcranial magnetic stimulation (high-frequency stimulation, 10 sessions or sham groups. Diffuse tensor tractography revealed partially injured spinothalamocortical tracts in all recruited patients. A numerical rating scale (NRS was used to evaluate pain intensity during pre-treatment and immediately after the 5th transcranial magnetic stimulation session (post1, 10th transcranial magnetic stimulation session (post2, and 1 (post3, 2 (post4, and 4 weeks (post 5 after finishing treatment. Physical and mental health status were evaluated using the Short Form 36 Health Survey (SF-36, including physical and mental component scores (PCS, MCS. Results: The NRS score of the repetitive transcranial magnetic stimulation group was significantly lower than the sham group score at all clinical evaluation time-points during and after transcranial magnetic stimulation sessions. The transcranial magnetic stimulation group’s SF-36 PCS score was significantly higher at post2, post3, post4, and post5 compared with the sham group. Conclusion: High-frequency transcranial magnetic stimulation may be used to manage chronic central pain and improve quality of life in patients with mild traumatic brain injury. However, this is a pilot study and further research is needed.

  9. Translation, Cultural Adaptation, and Validation of Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and Self-Complete Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) Questionnaires into the Greek Language.

    Science.gov (United States)

    Batistaki, Chrysanthi; Lyrakos, George; Drachtidi, Kalliopi; Stamatiou, Georgia; Kitsou, Maria-Chrysanthi; Kostopanagiotou, Georgia

    2016-06-01

    The LANSS and S-LANS