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.

Cannabis-based medicines for chronic neuropathic pain in adults.

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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

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

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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

Analgesic Microneedle Patch for Neuropathic Pain Therapy.

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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.

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.

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

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GURPREET KAUR

2015-03-01

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

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

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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.

Effects of fisetin on oxaliplatin-induced neuropathic pain in mice

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Hong Liu

2015-03-01

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

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

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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

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...

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

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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.

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.

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

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

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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®

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...

Chronic Orofacial Pain: Burning Mouth Syndrome and Other Neuropathic Disorders

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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

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.

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

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.

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...

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.

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

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.

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

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.

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

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

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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.

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

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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.

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...

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

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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.

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

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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.

Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

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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.

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.

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.

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

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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.

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

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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.

The Impact of Enrollment in a Specialized Interdisciplinary Neuropathic Pain Clinic

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Alex Garven

2011-01-01

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

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

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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

The evidence for pharmacological treatment of neuropathic pain.

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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.

Spinal interleukin-10 therapy to treat peripheral neuropathic pain.

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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.

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

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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.

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.

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

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Lim, Eun Yeong; Kim, Yun Tai

2016-01-01

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

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

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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.

Neuropathic pain in spinal cord injury.

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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

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

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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.

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.

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

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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.

Pharmacologic management of neuropathic pain.

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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.

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:.

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...

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)

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

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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.

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

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

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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.

TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States

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Laura Batti

2016-06-01

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

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) ...

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

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

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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.

Fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome.

Science.gov (United States)

Simons, Laura E

2016-02-01

A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Because of faulty nerve signaling, individuals with neuropathic pain and complex regional pain syndrome may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to downregulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, whereas high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear and evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with complex regional pain syndrome suggest breakthroughs in our ability to ameliorate these issues.

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.

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.

Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

Directory of Open Access Journals (Sweden)

Ming Liu

2014-01-01

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

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

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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.

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

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Helder eCardoso-Cruz

2011-08-01

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

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 ...

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-...

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

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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.

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.

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

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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.

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.

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

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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.

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

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

2017-05-01

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

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

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.

Tramadol for neuropathic pain in adults.

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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

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

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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.

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.

Characteristics of neuropathic pain in patients with spinal cord injury.

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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.

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...

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.

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

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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.

Melanocortins and Neuropathic Pain

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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

The neurosurgical treatment of neuropathic facial pain.

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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.

AAPT Diagnostic Criteria for Central Neuropathic Pain

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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...

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

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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.

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

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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.

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

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

2013-01-01

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

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

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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.

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

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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.

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 ...

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

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

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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.

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

An Algorithm for Neuropathic Pain Management in Older People.

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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.

Chronic pain in Gaucher disease: skeletal or neuropathic origin?

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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

Neuropathic pain and dry eye.

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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.

Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

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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.

Oxcarbazepine for neuropathic pain.

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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

Genitofemoral neuralgia: adding to the burden of chronic vulvar pain

Directory of Open Access Journals (Sweden)

Verstraelen H

2015-11-01

Full Text Available Hans Verstraelen,1 Eline De Zutter,1 Martine De Muynck2 1Department of Obstetrics and Gynaecology, Vulvovaginal Disease Clinic, Ghent University Hospital, Ghent, Belgium; 2Department of Physical Medicine and Rehabilitation, Ghent University Hospital, Ghent, Belgium Abstract: The vulva is a particularly common locus of chronic pain with neuropathic characteristics that occurs in women of any age, though most women with neuropathic type chronic vulvar pain will remain undiagnosed even following multiple physician visits. Here, we report on an exemplary case of a middle-aged woman who was referred to the Vulvovaginal Disease Clinic with debilitating vulvar burning and itching over the right labium majus that had been persisting for 2 years and was considered intractable. Careful history taking and clinical examination, followed by electrophysiological assessment through somatosensory evoked potentials was consistent with genitofemoral neuralgia, for which no obvious cause could be identified. Adequate pain relief was obtained with a serotonin–noradrenaline reuptake inhibitor and topical gabapentin cream. We briefly discuss the epidemiology, diagnosis, and treatment of genitofemoral neuralgia and provide a series of clues to guide clinicians in obtaining a presumptive diagnosis of specific neuropathic pain syndromes that may underlie chronic vulvar pain. We further aim to draw attention to the tremendous burden of chronic, unrecognized vulvar pain. Keywords: vulvar pain, genitofemoral nerve, neuropathic pain, vulvodynia, vulvar disease

Cross-Cultural Psychometric Assessment of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale in the Portuguese Population.

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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.

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

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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.

Molecular Hydrogen Attenuates Neuropathic Pain in Mice

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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

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

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

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

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

2016-03-01

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

Neuropathic orofacial pain: Facts and fiction.

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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.

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

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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

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

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

2000-01-01

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

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

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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.

Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain

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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.

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.

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

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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

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

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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

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

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

2017-06-01

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

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

Benfotiamine relieves inflammatory and neuropathic pain in rats.

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

2006-01-13

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

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

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

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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.

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.

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

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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.

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

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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.

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.

Topical amitriptyline and ketamine for the treatment of neuropathic pain.

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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.

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.

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

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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.

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.

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

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.

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

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Taverner, Tarnia

2015-08-01

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

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.

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

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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

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

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

2017-08-01

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

Spinal SIRT1 activation attenuates neuropathic pain in mice.

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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.

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

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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)

Activated microglia in the spinal cord underlies diabetic neuropathic pain.

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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.

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

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

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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.

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.

Combination treatment of neuropathic pain

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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...

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

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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.

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

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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.

Low-dose vaporized cannabis significantly improves neuropathic pain.

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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.

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

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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.

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

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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.

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

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Uher, Tomas; Bob, Petr

2013-03-01

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

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

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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

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

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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.

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

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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.

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 (.).

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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

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

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Arjun eMuralidharan

2016-05-01

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

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

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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.

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.

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

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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.

PHARMACOTHERAPY IN ELDERLY NEUROPATHIC PAIN

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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

A Single Sub-anesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats

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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

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

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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.

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

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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

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

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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.

An Algorithm for Neuropathic Pain Management in Older People

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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...

[Management of neuropathic pain].

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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.

Effects of fisetin on oxaliplatin-induced neuropathic pain in mice

OpenAIRE

Hong Liu; Chaohua Wang; Hua Yang; Fengjie Wang

2015-01-01

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

Altered Primary Motor Cortex Structure, Organization, and Function in Chronic Pain: A Systematic Review and Meta-Analysis.

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Chang, Wei-Ju; O'Connell, Neil E; Beckenkamp, Paula R; Alhassani, Ghufran; Liston, Matthew B; Schabrun, Siobhan M

2018-04-01

Chronic pain can be associated with movement abnormalities. The primary motor cortex (M1) has an essential role in the formulation and execution of movement. A number of changes in M1 function have been reported in studies of people with chronic pain. This review systematically evaluated the evidence for altered M1 structure, organization, and function in people with chronic pain of neuropathic and non-neuropathic origin. Database searches were conducted and a modified STrengthening the Reporting of OBservational studies in Epidemiology checklist was used to assess the methodological quality of included studies. Meta-analyses, including preplanned subgroup analyses on the basis of condition were performed where possible. Sixty-seven studies (2,290 participants) using various neurophysiological measures were included. There is conflicting evidence of altered M1 structure, organization, and function for neuropathic and non-neuropathic pain conditions. Meta-analyses provided evidence of increased M1 long-interval intracortical inhibition in chronic pain populations. For most measures, the evidence of M1 changes in chronic pain populations is inconclusive. This review synthesizes the evidence of altered M1 structure, organization, and function in chronic pain populations. For most measures, M1 changes are inconsistent between studies and more research with larger samples and rigorous methodology is required to elucidate M1 changes in chronic pain populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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...

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.

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...

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

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

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

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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.

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.

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

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

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

2014-03-01

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

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

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

2012-08-01

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

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 ...

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.

Internal and external factors affecting the development of neuropathic pain in rodents. Is it all about pain?

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Vissers, K; De Jongh, R; Hoffmann, V; Heylen, R; Crul, B; Meert, T

2003-12-01

It is important to know the factors that will influence animal models of neuropathic pain. A good reproducibility and predictability in different strains of animals for a given test increases the clinical relevance and possible targeting. An obligatory requirement for enabling comparisons of results of different origin is a meticulous definition of the specific sensitivities of a model for neuropathic pain and a description of the test conditions. Factors influencing neuropathic pain behavior can be subdivided in external and internal factors. The most important external factors are; timing of the measurement of pain after induction of neuropathy, circadian rhythms, seasonal influences, air humidity, influence of order of testing, diet, social variables, housing and manipulation, cage density, sexual activity, external stress factors, and influences of the experimenter. The internal factors are related to the type of animal, its genetic background, gender, age, and the presence of homeostatic adaptation mechanisms to specific situations or stress. In practice, the behavioral presentations to pain depend on the combination of genetic and environmental factors such as accepted social behavior. It also depends on the use of genetic manipulation of the animals such as in transgenic animals. These make the interpretation of data even more difficult. Differences of pain behavior between in- and outbred animals will be better understood by using modern analysis techniques. Substrains of animals with a high likelihood for developing neuropathic pain make the unraveling of specific pathophysiological mechanisms possible. Concerning the effect of stress on pain, it is important to differentiate between external and internal stress such as social coping behavior. The individual dealing with this stress is species sensitive, and depends on the genotype and the social learning. In the future, histo-immunological and genetic analysis will highlight similarities of the different

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

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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.

Reports of chronic pain in childhood and adolescence among patients at a tertiary care pain clinic.

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Hassett, Afton L; Hilliard, Paul E; Goesling, Jenna; Clauw, Daniel J; Harte, Steven E; Brummett, Chad M

2013-11-01

Although chronic pain in childhood can last into adulthood, few studies have evaluated the characteristics of adults with chronic pain who report childhood chronic pain. Thus, 1,045 new patients (mean age, 49.5 ± 15.4) at an academic tertiary care pain clinic were prospectively evaluated using validated self-report questionnaires. Patients also responded to questions about childhood pain. We found that almost 17% (n = 176) of adult chronic pain patients reported a history of chronic pain in childhood or adolescence, with close to 80% indicating that the pain in childhood continues today. Adults reporting childhood chronic pain were predominantly female (68%), commonly reported widespread pain (85%), and had almost 3 times the odds of meeting survey criteria for fibromyalgia (odds ratio [OR] = 2.94, 95% confidence interval [CI] = 2.04-4.23) than those denying childhood chronic pain. Similarly, those with childhood pain had twice the odds of having biological relatives with chronic pain (OR = 2.03, 95% CI = 1.39-2.96) and almost 3 times the odds of having relatives with psychiatric illness (OR = 2.85, 95% CI = 1.97-4.11). Lastly, compared to patients who did not report childhood chronic pain, those who did were more likely to use neuropathic descriptors for their pain (OR = 1.82, 95% CI = 1.26-2.64), have slightly worse functional status (B = -2.12, t = -3.10, P = .002), and have increased anxiety (OR = 1.77, 95% CI = 1.24-2.52). Our study revealed that 1 in 6 adult pain patients reported pain that dated back to childhood or adolescence. In such patients, evidence suggested that their pain was more likely to be widespread, neuropathic in nature, and accompanied by psychological comorbidities and decreased functional status. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

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.

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

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

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

2015-08-01

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

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

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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.

Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

DEFF Research Database (Denmark)

Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

2008-01-01

Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

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.

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

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Truini, Andrea; Cruccu, Giorgio

2016-02-01

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

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

African Journals Online (AJOL)

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

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.

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

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

2017-03-01

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

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.

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.

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.

Interventional therapy for neuropathic pain

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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.

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

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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

Pain relief with lidocaine 5% patch in localized peripheral neuropathic pain in relation to pain phenotype

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Torgaard Demant, Dyveke; Lund, Karen; Finnerup, Nanna B

2015-01-01

In neuropathic pain with irritable nociceptor phenotype, up-regulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype-panel, cross-over study with 4-week treatment pe...... had an effect on peripheral neuropathic pain, and it may be most efficacious in patients with irritable nociceptor phenotype. The lack of significant phenotype differences may be caused by too low statistical power.......In neuropathic pain with irritable nociceptor phenotype, up-regulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype-panel, cross-over study with 4-week treatment...... periods of lidocaine 5% patch and placebo was performed to search for phenotype differences in effect. The primary efficacy measure was the total pain intensity on an 11-point numeric rating scale (NRS), and the primary objective was to compare the effect of lidocaine in patients with and without...

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

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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.

Subtle alterations in brain anatomy may change an individual's personality in chronic pain.

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Sylvia M Gustin

Full Text Available It is well established that gross prefrontal cortex damage can affect an individual's personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual's personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual's personality.

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

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

2015-01-01

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

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

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

2016-03-01

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

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

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

2014-01-01

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

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

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

2015-01-01

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

rTMS of the prefrontal cortex has analgesic effects on neuropathic pain in subjects with spinal cord injury.

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Nardone, R; Höller, Y; Langthaler, P B; Lochner, P; Golaszewski, S; Schwenker, K; Brigo, F; Trinka, E

2017-01-01

Repetitive transcranial magnetic stimulation study. The analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain have been the focus of several studies. In particular, rTMS of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) changes pain perception in healthy subjects and has analgesic effects in acute postoperative pain, as well as in fibromyalgia patients. However, its effect on neuropathic pain in patients with traumatic spinal cord injury (SCI) has not been assessed. Merano (Italy) and Salzburg (Austria). In this study, we performed PMC/DLPFC rTMS in subjects with SCI and neuropathic pain. Twelve subjects with chronic cervical or thoracic SCI were randomized to receive 1250 pulses at 10 Hz rTMS (n=6) or sham rTMS (n=6) treatment for 10 sessions over 2 weeks. The visual analog scale, the sensory and affective pain rating indices of the McGill Pain Questionnaire (MPQ), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to assed pain and mood at baseline (T0), 1 day after the first week of treatment (T1), 1 day (T2), 1 week (T3) and 1 month (T4) after the last intervention. Subjects who received active rTMS had a statistically significant reduction in pain symptoms in comparison with their baseline pain, whereas sham rTMS participants had a non-significant change in daily pain from their baseline pain. The findings of this preliminary study in a small patient sample suggest that rTMS of the PMC/DLPFC may be effective in relieving neuropathic pain in SCI patients.

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

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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.

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.

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

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Valerio Magnaghi

2014-01-01

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

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

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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.

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

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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.

Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

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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.

The application of neuropathic pain questionnaires in burning mouth syndrome patients.

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Heo, Jun-Young; Ok, Soo-Min; Ahn, Yong-Woo; Ko, Myung-Yun; Jeong, Sung-Hee

2015-01-01

To evaluate and compare the validity of the PainDETECT, DN4, and abbreviated DN4 (DN4i) neuropathic pain questionnaires for primary burning mouth syndrome (BMS), which is a burning sensation in the oral mucosa in the absence of any identifiable organic etiology. Eighty-one patients (42 with primary BMS and 39 with nociceptive pain) complaining of a burning sensation and pain in their oral mucosa were enrolled in this study. All of the patients completed the neuropathic pain questionnaires. The sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic (ROC) curve were estimated. Then the relationship between pain intensity and total neuropathic pain score was investigated. Data were analyzed with the chi-square test and independent t test for subjects' baseline characteristic differences, and with Pearson correlation coefficients for the relationship of variables. The mean area under the ROC curves (AUCs) for PainDETECT, DN4, and DN4i were 0.81, 0.79, and 0.81, respectively. There was no statistically significant difference in the AUCs among the questionnaires. PainDETECT, DN4, and DN4i had a lower sensitivity and specificity for BMS compared to previous validation studies. The total scores for PainDETECT, DN4, and DN4i in the primary BMS group were significantly associated with pain intensity. Although the results of this study suggest that neuropathic pain questionnaires, such as PainDETECT and DN4, are not ideal principal screening tools for BMS patients, a substantial proportion of neuropathic symptoms in primary BMS patients were identified.

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.

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

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

2010-01-01

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

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

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Philipp Bishay

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

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

Treatment for chronic low back pain: the focus should change to multimodal management that reflects the underlying pain mechanisms.

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Müller-Schwefe, Gerhard; Morlion, Bart; Ahlbeck, Karsten; Alon, Eli; Coaccioli, Stefano; Coluzzi, Flaminia; Huygen, Frank; Jaksch, Wolfgang; Kalso, Eija; Kocot-Kępska, Magdalena; Kress, Hans-Georg; Mangas, Ana Cristina; Margarit Ferri, Cesar; Mavrocordatos, Philippe; Nicolaou, Andrew; Hernández, Concepción Pérez; Pergolizzi, Joseph; Schäfer, Michael; Sichère, Patrick

2017-07-01

Chronic low back pain: Chronic pain is the most common cause for people to utilize healthcare resources and has a considerable impact upon patients' lives. The most prevalent chronic pain condition is chronic low back pain (CLBP). CLBP may be nociceptive or neuropathic, or may incorporate both components. The presence of a neuropathic component is associated with more intense pain of longer duration, and a higher prevalence of co-morbidities. However, many physicians' knowledge of chronic pain mechanisms is currently limited and there are no universally accepted treatment guidelines, so the condition is not particularly well managed. Diagnosis should begin with a focused medical history and physical examination, to exclude serious spinal pathology that may require evaluation by an appropriate specialist. Most patients have non-specific CLBP, which cannot be attributed to a particular cause. It is important to try and establish whether a neuropathic component is present, by combining the findings of physical and neurological examinations with the patient's history. This may prove difficult, however, even when using screening instruments. Multimodal management: The multifactorial nature of CLBP indicates that the most logical treatment approach is multimodal: i.e. integrated multidisciplinary therapy with co-ordinated somatic and psychotherapeutic elements. As both nociceptive and neuropathic components may be present, combining analgesic agents with different mechanisms of action is a rational treatment modality. Individually tailored combination therapy can improve analgesia whilst reducing the doses of constituent agents, thereby lessening the incidence of side effects. This paper outlines the development of CLBP and the underlying mechanisms involved, as well as providing information on diagnosis and the use of a wide range of pharmaceutical agents in managing the condition (including NSAIDs, COX-2 inhibitors, tricyclic antidepressants, opioids and

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

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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

Spinal cord stimulation of dorsal columns in a rat model of neuropathic pain: evidence for a segmental spinal mechanism of pain relief.

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Smits, H; van Kleef, M; Joosten, E A

2012-01-01

Although spinal cord stimulation (SCS) of the dorsal columns is an established method for treating chronic neuropathic pain, patients still suffer from a substantial level of pain. From a clinical perspective it is known that the location of the SCS is of pivotal importance, thereby suggesting a segmental spinal mode of action. However, experimental studies suggest that SCS acts also through the modulation of supraspinal mechanisms, which might suggest that the location is unimportant. Here we investigated the effect of the rostrocaudal location of SCS stimulation and the effectiveness of pain relief in a rat model of chronic neuropathic pain. Adult male rats (n=45) were submitted to a partial ligation of the sciatic nerve. The majority of animals developed tactile hypersensitivity in the nerve lesioned paw. All allodynic rats were submitted to SCS (n=33) for 30 minutes (f=50 Hz; pulse width 0.2 ms). In one group (n=16) the electrodes were located at the level where the injured sciatic nerve afferents enter the spinal cord (T13), and in a second group (n=17) the electrodes were positioned at more rostral levels (T11) as verified by X-ray. A repositioning experiment of electrodes from T12 to T13 was performed in 2 animals. Our data demonstrate that SCS of the dorsal columns at the level where the injured fibers enter the spinal cord dorsal horn result in a much better pain-relieving effect than SCS at more rostral levels. From this we conclude that SCS in treatment of neuropathic pain acts through a segmental spinal site of action. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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.

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

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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.

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

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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.

Evaluation of the protein biomarkers and the analgesic response to systemic methylene blue in patients with refractory neuropathic pain: a double-blind, controlled study

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Miclescu AA

2015-07-01

Full Text Available Adriana A Miclescu,1 Martin Svahn,1 Torsten E Gordh1,2 1Multidisciplinary Pain Clinic, Uppsala University Hospital, 2Pain Research, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden Aim: This study was carried out in patients with neuropathic pain in order to assess the analgesic effects and changes in protein biomarkers after the administration of methylene blue (MB, a diaminophenothiazine with antioxidant and anti-inflammatory properties, and with inhibitory effects on nitric oxide.Materials and methods: Ten patients with chronic refractory neuropathic pain were randomized to receive either MB (10 mg/mL Methylthioninium chloride 2 mg/kg (MB group or MB 0.02 mg/kg (control group infused over 60 minutes. Sensory function and pain (Numerical Rating Scale were evaluated at baseline and at 60 minutes after the start of the infusion. The patients kept a pain diary during the next 24 hours and for the following 4 days. Plasma and urinary concentrations of 8-isoprostane-prostaglandin F2α (8-iso-PGF2α and plasma protein biomarkers prior to and after the infusions were measured with radioimmunoassay and with proximity extension assay.Results: A decrease of the Numerical Rating Scale at 60 minutes in comparison with baseline was observed in the MB (P=0.047 group. The decrease was significant between the MB and the control group on the day of and day after MB infusion (P=0.04 and P=0.008, respectively. There was no difference in systemic protein expressions between groups except for prolactin (PRL (P=0.02. Three patients demonstrated diminished dynamic mechanical allodynia.Conclusion: MB decreased the pain levels in patients with chronic therapy-resistant neuropathic pain on the first 2 days after administration. Known as an endocrine modulator on the anterior pituitary gland, MB infusion produced a decrease of PRL. The detailed role of PRL effects in chronic neuropathic pain remains undetermined.Keywords: methylene blue, nitric oxide

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

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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.

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

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

2016-08-25

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

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

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Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

2014-01-01

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

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

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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.

Antinociception induced by rosuvastatin in murine neuropathic pain.

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

2018-06-01

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

TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain.

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Rosen, John M; Yaggie, Ryan E; Woida, Patrick J; Miller, Richard J; Schaeffer, Anthony J; Klumpp, David J

2018-05-08

The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.

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

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

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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

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

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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...

Prevalence of pain and relative diagnostic performance of screening tools for neuropathic pain in cancer patients: A cross-sectional study.

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Pérez, C; Sánchez-Martínez, N; Ballesteros, A; Blanco, T; Collazo, A; González, F; Villoria, J

2015-07-01

Neuropathic pain can be overlooked in cancer patients. The advent of screening tools can help in recognizing it. However, little is known about their relative diagnostic performance and factors that affect it. This study evaluated the prevalence of neuropathic pain using several diagnostic strategies in cancer patients undergoing chemotherapy. Patients attending the Oncology Unit of the investigators' site to continue their chemotherapy schedule were systematically screened for this cross-sectional study. Before starting chemotherapy drugs, pain specialists made a clinical diagnosis of neuropathic pain (either disease related, treatment related or comorbid) and medical oncologists administered three validated screening tools. Their relative diagnostic performance and the impact of some pain features on it were analysed using multivariate statistical methods. From a total of 358 patients, 194 (54.2%) suffered from pain and 73 (20.4%) had a clinical diagnosis of pure neuropathic or mixed pain. Among the screening tools, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was more specific (93.4%), although less sensitive (68.1%) than the Douleur Neuropathique in 4 Questions (DN4) (sensitivity: 87.5%, specificity: 88.4%). Interestingly, the specificities of these two instruments did not differ in patients with mild pain, while the DN4 remained to be more sensitive than the LANSS regardless of pain severity. Neuropathic pain is common in cancer patients undergoing chemotherapy. The DN4 might be of great help for the early detection of patients at risk because of incipient chemotherapy-related neuropathies and the LANSS to rule out neuropathic pain in patients with complex pain conditions. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

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

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

2011-01-01

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

Neuropathic pain characteristics in patients from Curitiba (Brazil) with spinal cord injury.

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Vall, Janaína; Costa, Carlos Mauricio de Castro; Santos, Terezinha de Jesus Teixeira; Costa, Samuel Bovy de Castro

2011-02-01

This was a descriptive cross-sectional study on patients with spinal cord injuries living in Curitiba, Paraná, Brazil. The aim was to evaluate the pain characteristics among such patients seen at referral care centers for spinal cord injury patients in Curitiba. A total of 109 adults with spinal cord injury in this city were evaluated regarding the presence of pain, especially neuropathic pain. Neuropathic pain was evaluated using the DN4 questionnaire, a universal instrument that has been translated and validated for Portuguese. A visual analog scale (VAS) was used to evaluate the intensity of pain. The prevalence of pain among these 109 patients was 31.2% (34 patients). The nociceptive pain presented was classified as musculoskeletal pain (nine patients), visceral pain (four patients) and mixed pain (one patient), thus totaling 14 patients (12.8%). Another 20 patients (18.3%) showed symptoms of neuropathic pain and fulfilled the criteria for neuropathic pain with scores greater than 4 out 10 in the DN4 questionnaire. Regarding the characteristics of the patients with neuropathic pain, most of them were male, younger than 40 years of age and paraplegic with incomplete lesions. They had become injured from 1 to more than 5 years earlier. The predominant etiology was gunshot wounds, and the intensity of their pain was high, with VAS scores greater than 5. This study partially corroborates other studies conducted on this subject. Studies of this type are important for understanding the profile of these patients, for the purpose of designing strategies for their rehabilitation, with a focus on the appropriate treatment and management of pain.

Neuropathic pain characteristics in patients from Curitiba (Brazil with spinal cord injury

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Janaína Vall

2011-02-01

Full Text Available This was a descriptive cross-sectional study on patients with spinal cord injuries living in Curitiba, Paraná, Brazil. The aim was to evaluate the pain characteristics among such patients seen at referral care centers for spinal cord injury patients in Curitiba. A total of 109 adults with spinal cord injury in this city were evaluated regarding the presence of pain, especially neuropathic pain. Neuropathic pain was evaluated using the DN4 questionnaire, a universal instrument that has been translated and validated for Portuguese. A visual analog scale (VAS was used to evaluate the intensity of pain. The prevalence of pain among these 109 patients was 31.2% (34 patients. The nociceptive pain presented was classified as musculoskeletal pain (nine patients, visceral pain (four patients and mixed pain (one patient, thus totaling 14 patients (12.8%. Another 20 patients (18.3% showed symptoms of neuropathic pain and fulfilled the criteria for neuropathic pain with scores greater than 4 out 10 in the DN4 questionnaire. Regarding the characteristics of the patients with neuropathic pain, most of them were male, younger than 40 years of age and paraplegic with incomplete lesions. They had become injured from 1 to more than 5 years earlier. The predominant etiology was gunshot wounds, and the intensity of their pain was high, with VAS scores greater than 5. This study partially corroborates other studies conducted on this subject. Studies of this type are important for understanding the profile of these patients, for the purpose of designing strategies for their rehabilitation, with a focus on the appropriate treatment and management of pain.

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

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

2016-01-01

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

The evidence for pharmacological treatment of neuropathic pain

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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...

Diagnosis and medical treatment of neuropathic pain in leprosy.

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

2016-08-08

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

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

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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.

Neuroimaging revolutionizes therapeutic approaches to chronic pain

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Borsook David

2007-09-01

Full Text Available Abstract An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1 Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2 Functional Imaging (fMRI that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI; (3 Chemical Imaging (Magnetic Resonance Spectroscopy or MRS has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain – it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS.

Pathogenesis of spinal cord injury induced edema and neuropathic pain: expression of multiple isoforms of wnk1.

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Ahmed, Mostafa M; Lee, HyunKyung; Clark, Zach; Miranpuri, Gurwattan S; Nacht, Carrie; Patel, Kush; Liu, Lisa; Joslin, Jiliian; Kintner, Douglus; Resnick, Daniel K

2014-07-01

Neuropathic pain (NP) is a common occurrence following spinal cord injury (SCI). Identification of specific molecular pathways that are involved in pain syndromes has become a major priority in current SCI research. We have investigated the role of a cation-dependent chloride transporter, Cl-regulatory protein Na(+)-K(+)-Cl(-) 1 (NKCC1), phosphorylation profile of NKCC1 and its specific involvement in neuropathic pain following contusion SCI (cSCI) using a rat model. Administration of the NKCC1 inhibitor bumetanide (BU) increases the mean hindpaw withdrawal latency time (WLT), thermal hyperalgesia (TH) following cSCI. These results demonstrate implication of NKCC1 co-transporter and BUin SCI-induced neuropathic pain. The with-no-lysine (K)-1 (WNK1) kinase has been shown to be an important regulator of NKCC1 phosphorylation in many systems, including nocioception. Mutations in a neuronal-specific exon of WNK1 (HSN2) was identified in patients that have hereditary sensory neuropathy type II (HSANII) also implicates WNK1 in nocioception, such that these patients have loss of perception to pain, touch and heat. In our ongoing research we proposed two studies utilizing our contusion SCI (cSCI) NP model of rat. Study 1 aimed at NKCC1 expression and activity is up-regulated following cSCI in the early edema and chronic neuropathic pain phases. Study 2 aimed at identifying the expression profile of alternatively spliced WNK1 isoforms in animals exhibiting thermal hyperalgesia (TH) following cSCI. Adult male Sprague Dawley rats (275-300 g) following laminectomy received cSCI at T9 with the NYU impactor-device II by dropping 10 g weight from the height of 12.5 mm. Control rats obtained laminectomy but no impaction. Following injury, functional recovery was assessed by BBB locomotor scores on day 1, 7, 14, 21, 35, and 42 and development of thermal hyperalgesia on day 21, 28, 35, and 42 day of injury by monitoring hind paw withdraw latency time (WLT) in seconds compared with

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

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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

Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

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Dallel Radhouane

2010-02-01

Full Text Available Abstract Background Chikungunya virus (CHIKV is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC in a pain syndrome is a major step towards pain control. Methods We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL. Results The mean intensity of pain on the visual-analogical scale (VAS was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65% of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0. However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ(15.5 ± 5.2 vs 11.6 ± 5.2; p Conclusions There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.

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.

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

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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...

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.

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.

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

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Casale R

2014-06-01

��drug interactions. Such patients benefit greatly from topical treatment of PHN. Our observations confirm the effectiveness of lidocaine plasters in the treatment of PHN, indicating that 5% lidocaine medicated plaster could reduce the size of the painful area. This last observation has to be confirmed and the mechanisms clarified in appropriate larger randomized controlled trials.Keywords: localized neuropathic pain, topical treatment, chronic pain, drug–drug interactions, patient's outcome

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

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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.

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

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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.

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

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

2002-01-01

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

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.

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

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

2016-07-11

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

Spinal cord stimulation and modulation of neuropathic pain

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de Vos, Cecilia Cecilia Clementine

2013-01-01

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

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

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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...

Epidemiology of chronic pain in the office of a pain specialist neurologist

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Karen dos Santos Ferreira

2015-07-01

Full Text Available Objective The objective of the present report was to describe the working experience of a pain specialist neurologist after concluding a medical residency program on neurology, area of concentration pain. Method A retrospective study was conducted for one year in the office of a pain specialist neurologist. Patients older than 18 years with chronic pain according to the criteria of the International Association for the Study of Pain, were included. Demographic data, chronic pain data and the treatments instituted were investigated. Results A total of 241 medical records were reviewed, mean patient age was 52.4 years and 79 (66.9% were women, and the mean score on a numeric pain scale was 8.69. The diagnoses were headaches (74.6%, neuropathic pain (17% and ostheomuscular pain (8.2%. We did not detect cancer pain. Patients received medication and procedures of anesthetic blockade. Conclusion This data can guide new medical residency programs on Neurology, area of concentration pain, to plan activities and studies.

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

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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.

Phenytoin Cream for the Treatment of Neuropathic Pain: Case Series

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David J. Kopsky

2018-05-01

Full Text Available BACKGROUND: Neuropathic pain can be disabling, and is often difficult to treat. Within a year, over half of all patients stop taking their prescribed neuropathic pain medication, which is most probably due to side effects or disappointing analgesic results. Therefore, new therapies are needed to alleviate neuropathic pain. As such, topical analgesics could be a new inroad in the treatment of neuropathic pain. In 2014, we developed a new topical formulation containing either phenytoin or sodium phenytoin. After optimization of the formulation, we were able to reach a 10% concentration and combine phenytoin with other co-analgesics in the same base cream. OBJECTIVE: To describe a series of 70 neuropathic pain patients who were treated with phenytoin cream. MATERIAL AND METHODS: Cases treated with phenytoin 5% or 10% creams were gathered. The mean onset of pain relief, the duration of effect, and reduction in pain intensity measured on the 11-point numerical rating scale (NRS were all studied. A single-blind response test with phenytoin 10% and placebo creams was conducted on 12 patients in order to select responders prior to prescribing the active cream. Plasma phenytoin concentrations were measured in 16 patients. RESULTS: Nine patients applied phenytoin 5% cream, and 61 patients used phenytoin 10% cream. After grouping the effects of all of the patients, the mean onset of pain relief was 16.3 min (SD: 14.8, the mean duration of analgesia was 8.1 h (SD: 9.1, and the mean pain reduction on the NRS was 61.2% (SD: 25.0. The mean pain reduction on the NRS while using phenytoin cream was statistically significant compared with the baseline, with a reduction of 4.5 (CI: 4.0 to 5.0, p < 0.01. The 12 patients on whom a single-blind response test was performed experienced a statistically significant reduction in pain in the area where the phenytoin 10% cream was applied in comparison to the area where the placebo cream was applied (p < 0.01. Thirty

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

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.

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

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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

Multi-dimensionality of chronic pain of the oral cavity and face

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2013-01-01

Orofacial pain in its broadest definition can affect up to 7% of the population. Its diagnosis and initial management falls between dentists and doctors and in the secondary care sector among pain physicians, headache neurologists and oral physicians. Chronic facial pain is a long term condition and like all other chronic pain is associated with numerous co-morbidities and treatment outcomes are often related to the presenting co-morbidities such as depression, anxiety, catastrophising and presence of other chronic pain which must be addressed as part of management . The majority of orofacial pain is continuous so a history of episodic pain narrows down the differentials. There are specific oral conditions that rarely present extra orally such as atypical odontalgia and burning mouth syndrome whereas others will present in both areas. Musculoskeletal pain related to the muscles of mastication is very common and may also be associated with disc problems. Trigeminal neuralgia and the rarer glossopharyngeal neuralgia are specific diagnosis with defined care pathways. Other trigeminal neuropathic pain which can be associated with neuropathy is caused most frequently by trauma but secondary causes such as malignancy, infection and auto-immune causes need to be considered. Management is along the lines of other neuropathic pain using accepted pharmacotherapy with psychological support. If no other diagnostic criteria are fulfilled than a diagnosis of chronic or persistent idiopathic facial pain is made and often a combination of antidepressants and cognitive behaviour therapy is effective. Facial pain patients should be managed by a multidisciplinary team. PMID:23617409

Newer N-phthaloyl GABA derivatives with antiallodynic and antihyperalgesic activities in both sciatic nerve and spinal nerve ligation models of neuropathic pain.

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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.

Elucidation of pathophysiology and treatment of neuropathic pain

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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

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

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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.

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

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

2015-04-01

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

STAT3 inhibitor WP1066 as a novel therapeutic agent for bCCI neuropathic pain rats.

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Xue, Zhao-Jing; Shen, Le; Wang, Zhi-Yao; Hui, Shang-Yi; Huang, Yu-Guang; Ma, Chao

2014-10-02

Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in the development of chronic pain, but the complex regulation of STAT3-dependent pathway and the functional significance of inhibiting this pathway during the development of neuropathic pain remain elusive. To evaluate the contribution of the JAK2/STAT3 pathway to neuropathic pain and the potentiality of this pathway as a novel therapeutic target, we examined the effects of the STAT3 inhibitor WP1066 by intrathecal administration in a rat model of bilateral chronic constriction injury (bCCI). The pain behavior tests were performed before the surgery and on postoperative day 3, 7, 14 and 21. L4-L6 dorsal spinal cord were harvested at each time point. Both RT-PCR and Western blot were performed to evaluate the activation of JAK2/STAT3 pathway. To observe the influence of WP1066 on neuropathic pain and its molecular mechanism, WP1066 (10 μl, 10 mmol/L in DMSO) or the same capacity of DMSO as the control were applied through the intrathecal tube on the day before bCCI surgery, and on the postoperative day 3 and 5. Behavioral tests were performed to observe the therapeutic effect on mechanical, thermal and cold hyperalgesia. L4-L6 dorsal spinal cord was harvested on postoperative day fourteen, followed by RT-PCR and Western blot evaluation of the JAK2/STAT3 pathway activation. The mechanical, thermal and cold hyperalgesia of the bCCI rats were significantly decreased when compared with the Sham or the Naïve group at each postoperative time point (PbCCI rats, accompanied by SOCS3 mRNA with a similar tendency. Western blot analysis showed that JAK2 and phosphorylated STAT3 increased significantly since 3 days after bCCI. JAK2 peaked on postoperative day 14 while phosphorylated STAT3 peaked on postoperative day 7 and gradually decreased thereafter and SOCS3׳s peak level on postoperative day 3. When WP1066 were administered intrathecally, the pain behaviors of

Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

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Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

2014-04-01

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

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

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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).

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.

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

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

2013-09-01

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

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

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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.

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

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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

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

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: screening and diagnosis recommendations.

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Mehta, S; Guy, S D; Bryce, T N; Craven, B C; Finnerup, N B; Hitzig, S L; Orenczuk, S; Siddall, P J; Widerström-Noga, E; Casalino, A; Côté, I; Harvey, D; Kras-Dupuis, A; Lau, B; Middleton, J W; Moulin, D E; O'Connell, C; Parrent, A G; Potter, P; Short, C; Teasell, R; Townson, A; Truchon, C; Wolfe, D; Bradbury, C L; Loh, E

2016-08-01

Clinical practice guidelines. To develop the first Canadian clinical practice guidelines for screening and diagnosis of neuropathic pain in people with spinal cord injury (SCI). The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. The CanPainSCI Working Group reviewed evidence to address clinical questions regarding screening and diagnosis of neuropathic pain after SCI. A consensus process was followed to achieve agreement on recommendations and clinical considerations. Twelve recommendations, based on expert consensus, were developed for the screening and diagnosis of neuropathic pain after SCI. The recommendations address methods for assessment, documentation tools, team member accountability, frequency of screening and considerations for diagnostic investigation. Important clinical considerations accompany each recommendation. The expert Working Group developed recommendations for the screening and diagnosis of neuropathic pain after SCI that should be used to inform practice.

Chronic Widespread Back Pain is Distinct From Chronic Local Back Pain: Evidence From Quantitative Sensory Testing, Pain Drawings, and Psychometrics.

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Gerhardt, Andreas; Eich, Wolfgang; Janke, Susanne; Leisner, Sabine; Treede, Rolf-Detlef; Tesarz, Jonas

2016-07-01

Whether chronic localized pain (CLP) and chronic widespread pain (CWP) have different mechanisms or to what extent they overlap in their pathophysiology is controversial. The study compared quantitative sensory testing profiles of nonspecific chronic back pain patients with CLP (n=48) and CWP (n=29) with and fibromyalgia syndrome (FMS) patients (n=90) and pain-free controls (n = 40). The quantitative sensory testing protocol of the "German-Research-Network-on-Neuropathic-Pain" was used to measure evoked pain on the painful area in the lower back and the pain-free hand (thermal and mechanical detection and pain thresholds, vibration threshold, pain sensitivity to sharp and blunt mechanical stimuli). Ongoing pain and psychometrics were captured with pain drawings and questionnaires. CLP patients did not differ from pain-free controls, except for lower pressure pain threshold (PPT) on the back. CWP and FMS patients showed lower heat pain threshold and higher wind-up ratio on the back and lower heat pain threshold and cold pain threshold on the hand. FMS showed lower PPT on back and hand, and higher comorbidity of anxiety and depression and more functional impairment than all other groups. Even after long duration CLP presents with a local hypersensitivity for PPT, suggesting a somatotopically specific sensitization of nociceptive processing. However, CWP patients show widespread ongoing pain and hyperalgesia for different stimuli that is generalized in space, suggesting the involvement of descending control systems, as also suggested for FMS patients. Because mechanisms in nonspecific chronic back pain with CLP and CWP differ, these patients should be distinguished in future research and allocated to different treatments.

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.

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

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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.

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.

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

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Andreas Binder

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

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

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Manoel Jacobsen Teixeira

2013-09-01

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

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

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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.

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

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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.

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.

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

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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.

Epidural spinal cord stimulation for neuropathic pain: a neurosurgical multicentric Italian data collection and analysis.

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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.

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

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Swetha Kanyadhara

2014-01-01

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

Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: the role of the locus coeruleus.

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Bravo, Lidia; Alba-Delgado, Cristina; Torres-Sanchez, Sonia; Mico, Juan Antonio; Neto, Fani L; Berrocoso, Esther

2013-10-01

Stressful experiences seem to negatively influence pain perception through as yet unknown mechanisms. As the noradrenergic locus coeruleus (LC) nucleus coordinates many components of the stress response, as well as nociceptive transmission, we evaluated whether the sensory and affective dimension of chronic neuropathic pain worsens in situations of stress due to adaptive changes of LC neurons. Accordingly, male rats were socially isolated for 5 weeks, and in the last 2 weeks, neuropathic pain was induced by chronic constriction injury. In this situation of stress, chronic pain selectively heightened the animal's aversion to painful experiences (affective pain), as measured in the place escape/avoidance test, although no changes were observed in the sensory dimension of pain. In addition, electrophysiological recordings of LC neurons showed a low tonic but exacerbated nociceptive-evoked activity when the injured paw was stimulated. These changes were accompanied by an increase in tyrosine hydroxylase and gephyrin expression in the LC. Furthermore, intra-LC administration of bicuculline, a γ-aminobutyric acid-A receptor antagonist, attenuated the negative affective effects of pain. These data show that changes in the LC are greater than those expected from the simple summation of each independent factor (pain and stress), revealing mechanisms through which stressors may exacerbate pain perception without affecting the sensorial dimension. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

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

2011-01-01

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

Evaluation of the Effect of Duration on the Efficacy of Pulsed Radiofrequency in an Animal Model of Neuropathic Pain.

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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.

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

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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

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.

Effects of electroacupuncture on orphanin FQ immunoreactivity and preproorphanin FQ mRNA in nucleus of raphe magnus in the neuropathic pain rats.

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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.

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.

Hypolocomotion, asymmetrically directed behaviors (licking, lifting, flinching, and shaking and dynamic weight bearing (gait changes are not measures of neuropathic pain in mice

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