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Background: Patients with neuropathic pain present with various pain-related sensory abnormalities. These sensory features form different patterns or mosaics-the sensory profile-in individual patients. One hypothesis for the development of sensory profiles is that distinct pathophysiological mechanisms of pain generation produce specific sensory abnormalities. Several controlled trials of promising new drugs have produced negative results, but these findings could have been a result of heterogeneity in the patient population. Subgrouping patients on the basis of individual sensory profiles could reduce this heterogeneity and improve trial design., Recent Developments: A statistical categorisation of patients with neuropathic pain showed that subgroups of patients with distinct sensory profiles who perceive their pain differently do exist across a range of neuropathic disorders, although some distinct disorder-specific profiles were also detected. Results of the first clinical trials to use the subgroup approach at baseline could show a superior effect of the study drugs in specific subgroups, rather than in the entire cohort of patients. WHERE NEXT?: A new classification of neuropathic pain should take into account subgroups of patients with different sensory profiles. Sensory phenotyping has the potential to improve clinical trial design by enriching the study population with potential treatment responders, and might lead to a stratified treatment approach and ultimately to personalised treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: Supraorbital neuralgia (SON) is an uncommon disorder characterized by pain in the area supplied by the supraorbital nerve, which covers the medial aspect of the forehead, together with tenderness over the supraorbital notch or along the course of the nerve. Few hospital-based series of non-trauma SON have been published., Methods and Results: We prospectively analyzed 13 patients (11 females, two males) diagnosed with SON in a headache outpatient clinic over a four-year period. Background pain was mostly dull and of moderate intensity. In addition, nine patients reported sharp, burning or stabbing exacerbations of severe intensity. Eight cases were treated with an anesthetic blockade and achieved complete relief lasting from two to six months. Three patients also received gabapentin, with no or only slight improvement., Conclusion: Non-traumatic SON is an uncommon disorder in our headache clinic. Female preponderance and clinical features are comparable to the data collected in previous studies. A spontaneously remitting pattern is not uncommon, and anesthetic blockades are not always required.

Background and Purpose: Despite the rapid development of neuropharmacotherapy, medical treatment of neuropathic pain (NP) still constitutes a significant socioeconomic problem. The authors herein present a group of patients treated with motor cortex stimulation (MCS) for NP of various types and aetiologies., Material and Methods: Our cohort included 12 female and 11 male NP patients aged 53 ± 16 treated with MCS. Eleven patients were diagnosed with neuropathic facial pain (NFP), 8 with hemi-body neuropathic pain (HNP), and 4 with deafferentation pain (DP). Prior to surgery, 16 out of 23 patients were treated with repetitive transcranial magnetic stimulation (rTMS), with a positive response in 10 cases. Pain intensity in our group was evaluated with the visual analogue scale (VAS) one month before and three months after MCS implantation., Results: Improvement on the VAS was reported in the whole group of patients (p < 0.001). The best results were reported in the NFP group (p < 0.001) while the worst ones were noted in the DP group (p = 0.04). Anamnesis duration positively correlated with outcome. Infection forced the authors to permanently remove the system in one case. There were no other complications in the group., Conclusions: Minimally invasive, safe neuromodulative treatment with MCS permits neuropathic pain control with good efficacy. The type of neuropathic pain might be a prognostic factor.

Background: Best current estimates of neuropathic pain (NeuP) prevalence come from studies using various screening detecting pain with probable neuropathic features; the proportion experiencing significant, long-term NeuP, and the proportion not responding to standard treatment are unknown. These "refractory" cases are the most clinically important to detect, being the most severe, requiring specialist treatment., Methods: We report an international Delphi survey of experts in NeuP, aiming for consensus on the features required to define, for epidemiological research: (1) neuropathic pain; and (2) when NeuP is "refractory". A web-based questionnaire was developed and data collected from three rounds of questionnaires from nineteen experts., Results: There was good consensus on essential inclusion of six items to identify NeuP ("prickling, tingling, pins & needles", "pain evoked by light touch", "electric shocks or shooting pain", "hot or burning" pain, "brush allodynia on self-examination", and "relevant history") and on some items that were non-essential. Consensus was also reached on components of a "refractory NeuP" definition: minimum duration (one year); number of trials of drugs of known effectiveness (four); adequate duration of these trials (three months / maximum tolerated); outcomes of treatment (pain severity, quality of life). Further work needs to validate these proposed criteria in general population research., Conclusions: This paper presents an international consensus on measuring the epidemiology of refractory neuropathic pain. This will be valuable in reaching an agreed estimate of the prevalence of neuropathic pain, and the first estimate of refractory neuropathic pain prevalence.

Background: Neuropathic pain questionnaires are efficient diagnostic tools for neuropathic pain and play an important role in neuropathic pain epidemiologic studies in China. No comparison data was available in regards to the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), the Neuropathic Pain Questionnaire (NPQ) and ID Pain within and among the same population., Objective: To achieve a linguistic adaptation, validation, and comparison of Chinese versions of the 3 neuropathic pain questionnaires (LANSS, NPQ and ID Pain)., Study Design: A nonrandomized, controlled, prospective, multicenter trial., Setting: Ten pain centers in China., Methods: Two forward translations followed by comparison and reconciliation of the translations. Comparison of the 2 backward translations with the original version was made to establish consistency and accuracy of the translations. Pilot testing and pain specialists' evaluations were also required. A total of 140 patients were enrolled in 10 centers throughout China: 70 neuropathic pain patients and 70 nociceptive pain patients. Reliability (Cronbach's alpha coefficients and Guttman split-half coefficients) and validity (sensitivity, specificity, positive and negative predictive values, receiver operating characteristic [ROC] curves and the area under the ROC curves) of the 3 questionnaires were determined. ROC curves and the area under the ROC curves of the 3 questionnaires were also compared., Results: Chinese versions of LANSS, NPQ and ID Pain had a good reliability (Cronbach's alpha coefficients and Guttman split-half coefficients were greater than 0.7). Sensitivity, specificity, positive and negative predictive values of the Chinese versions of LANSS and ID Pain were considerably high ( > 80%). The area under the ROC curves of LANSS and ID Pain was significantly higher than that of NPQ (P < 0.05). There was no statistically significant difference between the area under the ROC curves of LANSS and ID Pain (P > 0.05)., Limitation: The study was based on patients with a high school degree or above, which limited the application of the 3 neuropathic pain questionnaires to patients with lower educational levels., Conclusion: The Chinese versions of LANSS and ID Pain developed and validated by this study can be used as a diagnostic tool in differentiating neuropathic pain in patients whose native language is Chinese (Mandarin).

Objective: The self-report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and Douleur Neuropathique 4 Questions (DN4) neuropathic pain screening tools have been shown to be reliable, valid, and able to differentiate neuropathic pain from inflammatory or mixed pain syndromes. However, no studies have compared these tools to determine whether their outcomes are similar. This study evaluated agreement and correlation between the S-LANSS and DN4 in the identification of neuropathic pain in subjects with low back-related leg pain., Methods: This observational study compared S-LANSS and DN4 scores in 45 patients with low back-related leg pain. The S-LANSS and DN4 cutoff scores of 12 and 4, respectively, were used to classify subjects as positive or negative for the presence of neuropathic pain for each screening tool. The κ statistic was used to determine whether there was agreement in classification of neuropathic pain between the 2 screening tools. Pearson correlation coefficient was used to determine correlation between scores of the 2 screening tools., Results: Neuropathic pain was identified in 15 subjects (33%) using the S-LANSS and in 19 subjects (42%) using the DN4. Agreement on neuropathic pain classification was fair, with a κ value of 0.34. There was moderate to good correlation (r = 0.62; P < .001) between scores obtained from the 2 tools., Conclusions: The finding of fair agreement suggests that despite the moderate to good correlation between scores, the cutoff points for the classification of neuropathic pain of the 2 tools may not be congruent., (Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.)

Persistent postoperative pain is a common complication of surgery, including surgical interventions for cancer. So far, there is limited information about the prevalence and clinical characteristics of pain after lymph node biopsy and dissection in patients with malignant melanoma. In this study, a questionnaire was sent out to all surviving patients (n=402) after surgery for cutaneous malignant melanoma at the Aalborg Hospital Department of Plastic Surgery, Aalborg, Denmark. Of patients responding, sentinel node biopsy (SNB) and/or lymph node dissection (LND) was performed in 175 patients. All patients with pain and a control group were invited to a clinical examination. Altered sensation and pain were significantly more common after LND (82% and 34%, respectively) than after SNB (32% and 14%, respectively). In patients with LND, 12% reported at least moderate pain and 14% impact of pain on quality of life, while in patients with SNB, 3% reported at least moderate pain and 2% pain impact on quality of life. The most important predictor of pain was sensory abnormalities. At the clinical follow-up, 10 out of 12 patients with pain both met the criteria of the recently proposed grading system for probable neuropathic pain and used descriptors on the DN4 questionnaire suggestive of neuropathic pain. Different patterns of sensory profiles were observed in single patients, suggesting heterogeneous sensory processing within single patients. This study suggested that nerve injury was the main underlying mechanism of persistent pain after lymph node excision., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Some patients develop excessive peripheral nerve pain beyond that normally experienced after injury or surgery. Managing this pain can be a difficult and frustrating experience for both the surgeon and patient concerned. We present a system for the classification, assessment and treatment of painful neuromas of the upper limb.

Introduction: Multiple sclerosis (MS) is an inflammatory, demyelinating, central nervous system disease that frequently causes pain., Areas Covered: This article reviews the current literature and describes the therapeutic options for treating MS-related pain. The reader will be provided with current, evidence-based knowledge about the treatment of MS-related pain, and the review will take a practical approach to the various drugs for treating pain, including starting dose, titration and side effects., Expert Opinion: Only cannabinoids have been assessed in randomized, controlled trials. Because of the concern regarding the risk of abuse and psychiatric adverse events, published guidelines as well as expert recommendations suggest using them as second-line therapy only. Hence, current treatment should be based on the general principles for treating peripheral neuropathic pain, taking into account drug-induced adverse effects.

Are viruses responsible for the pain in patients with fibromyalgia? Are viruses the trigger for rheumatoid arthritis? Is chronic fatigue syndrome a viral disease? There are many open questions with few or controversial answers. According to the current state of knowledge on the origin of the pain in fibromyalgia the varied symptomatic of fibromyalgia is triggered by peripheral as well as central mechanisms. Despite the broad spectrum of symptoms the disease is a specific entity which is mainly treated with dual reuptake inhibitors, anticonvulsives, tramadol, selective serotonin reuptake inhibitors, gamma-hydroxybutyrate and dopamine agonists in individually selected combinations.

The statins are a well-established class of drugs that lower plasma cholesterol levels by inhibiting HMG-CoA (3-hydroxy-3-methyl-glutaryl-coenzyme A) reductase. They are widely used for the treatment of hypercholesterolemia and for the prevention of coronary heart disease. Recent studies suggest that statins have anti-inflammatory effects beyond their lipid-lowering properties. We sought to investigate whether statins could affect neuropathic pain by mediating nerve injury-associated inflammatory responses. The effects of hydrophilic rosuvastatin and lipophilic simvastatin were examined in the mouse partial sciatic nerve ligation model. Systemic daily administration of either statin from days 0 to 14 completely prevented the development of mechanical allodynia and thermal hyperalgesia. When administered from days 8 to 14 after injury, both statins dose-dependently reduced established hypersensitivity. After treatment, the effects of the statins were washed out within 2 to 7 days, depending on dose. Effects of both statins in alleviating mechanical allodynia were further confirmed in a different injury-associated neuropathic pain model, mental nerve chronic constriction, in rats. Both statins were able to abolish interleukin-1β expression in sciatic nerve triggered by nerve ligation. Additionally, quantitative analysis with Iba-1 and glial fibrillary acid protein immunoreactivity demonstrated that rosuvastatin and simvastatin significantly reduced the spinal microglial and astrocyte activation produced by sciatic nerve injury. The increase of interleukin-1β mRNA in the ipsilateral side of spinal cords was also reduced by the treatment of either statin. We identified a potential new application of statins in the treatment of neuropathic pain. The pain-alleviating effects of statins are likely attributable to their immunomodulatory effects., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze the incidence and characteristics of the first 1000 headaches in an outpatient clinic., Background: Headache is a common cause of medical consultation, both in primary care and in specialist neurology outpatient clinics. The International Classification of Headache Disorders, 2nd Edition (ICHD-II), enables headaches to be classified in a precise and reproducible manner., Methods: In January 2008, an outpatient headache clinic was set up in Hospital Clínico Universitario, a tertiary hospital in Valladolid, Spain. Headaches were classified prospectively in accordance with ICHD-II criteria. In each case we recorded age and sex, duration of headache, ancillary tests required, and previous symptomatic or prophylactic therapies., Results: In January 2010, the registry included 1000 headaches in 682 patients. The women/men ratio was 2.46/1 and the mean age of the patients was 43.19 ± 17.1 years (range: 14-94 years). Patients were referred from primary care (53.4%), general neurology clinics (36.6%), and other specialist clinics (9%). The headaches were grouped (ICHD-II classification) as follows: group 1 (Migraine), 51.4%; group 2 (Tension-type headache), 16%; group 3 (Trigeminal autonomic cephalalgias), 2.6%; group 4 (Other primary headaches) and group 13 (Cranial neuralgias), 3.4%. The diagnostic criteria of chronic migraine were satisfied in 8.5% of migraines. Regarding secondary headaches, 1.1% of all cases were included in group 5 (Headaches attributed to trauma) and 8.3% in group 8 (Headaches attributed to a substance or its withdrawal). Only 3.4% of headaches were classified in group 14 (Unspecified or not elsewhere classified), and 5.2% were included in the groups listed in the ICHD-II research appendix., Conclusion: This registry outlines the characteristics of patients seen in an outpatient headache clinic in a tertiary hospital; our results are similar to those previously reported for this type of outpatient clinic. Migraine was the most common diagnosis. Most headaches can be classified using ICHD-II criteria., (© 2011 American Headache Society.)

The purpose of this paper is to provide the reader with evidence basedclinical guidance regarding assessing neuropathic pain. Persistent pain is a huge burden on health-care provision and the prevalence of persistent neuropathic pain is likely to increase owing to the ageing population. The provision of appropriate relieving interventions depends on accurate assessment. This paper sets out to provide the reader with simple neuropathic assessment tools that can be applied to community care. This will allow the community nurse to identify patients who have neuropathic pain and will therefore enable appropriate management.

Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up to 18% for mechanical stimuli). Mechanical hyperalgesias occurred more often (blunt pressure: 36%, pinprick: 29%) than thermal hyperalgesias (cold: 19%, heat: 24%), dynamic mechanical allodynia (20%), paradoxical heat sensations (18%) or enhanced wind-up (13%). Hyperesthesia was less than 5%. Every single sensory abnormality occurred in each neurological syndrome, but with different frequencies: thermal and mechanical hyperalgesias were most frequent in complex regional pain syndrome and peripheral nerve injury, allodynia in postherpetic neuralgia. In postherpetic neuralgia and in central pain, subgroups showed either mechanical hyperalgesia or mechanical hypoalgesia. The most frequent combinations of gain and loss were mixed thermal/mechanical loss without hyperalgesia (central pain and polyneuropathy), mixed loss with mechanical hyperalgesia in peripheral neuropathies, mechanical hyperalgesia without any loss in trigeminal neuralgia. Thus, somatosensory profiles with different combinations of loss and gain are shared across the major neuropathic pain syndromes. The characterization of underlying mechanisms will be needed to make a mechanism-based classification feasible., (Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

In patients with distal symmetric polyneuropathy we assessed non-nociceptive Abeta- and nociceptive Adelta-afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 150 patients with distal symmetric polyneuropathy (68 with pain and 82 without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard nerve conduction study (NCS) to assess Abeta-fibre function, and laser-evoked potentials (LEPs) to assess Adelta-fibre function. Patients with pain had the same age (P>0.50), but a longer delay since symptom onset than those without (P<0.01). Whereas the LEP amplitude was significantly lower in patients with pain than in those without (P<0.0001), NCS data did not differ between groups (P>0.50). LEPs were more severely affected in patients with ongoing pain than in those with provoked pain (P<0.0001). Our findings indicate that the impairment of Abeta-fibres has no role in the development of ongoing or provoked pain. In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that this type of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism-based grounds., (Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: This second European Federation of Neurological Societies Task Force aimed at updating the existing evidence about the pharmacological treatment of neuropathic pain since 2005., Methods: Studies were identified using the Cochrane Database and Medline. Trials were classified according to the aetiological condition. All class I and II randomized controlled trials (RCTs) were assessed; lower class studies were considered only in conditions that had no top-level studies. Treatments administered using repeated or single administrations were considered, provided they are feasible in an outpatient setting., Results: Most large RCTs included patients with diabetic polyneuropathies and post-herpetic neuralgia, while an increasing number of smaller studies explored other conditions. Drugs generally have similar efficacy in various conditions, except in trigeminal neuralgia, chronic radiculopathy and HIV neuropathy, with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions). Combination therapy appears useful for TCA-gabapentin and gabapentin-opioids (level A)., Conclusions: There are still too few large-scale comparative studies. For future trials, we recommend to assess comorbidities, quality of life, symptoms and signs with standardized tools and attempt to better define responder profiles to specific drug treatments.

Despite ongoing efforts, neither effective treatments nor mechanistic understanding of the pathogenesis of human neuropathic pain exists. Genetic association studies may point to the novel molecules that mediate neuropathic pain, facilitating its understanding and management. Several studies used a candidate gene approach to elucidate genetic contribution to neuropathic pain phenotypes; however, the data is limited and inconsistent. Possible reasons include: sample heterogeneity, underpowered study design, population admixture, poor phenotyping, genotyping errors, and statistical analytical mistakes. This article summarizes and discusses current strategies to optimize population-based association studies of human neuropathic pain focusing on principles of measuring neuropathic pain phenotypes and genotyping techniques. We also consider advantages and challenges of study designs and statistical analyses.

Neuropathic pain is relatively uncommon in children. Although some syndromes closely resemble those found in adults, the incidence and course of the condition can vary substantially in children, depending on developmental status and contextual factors. There are some neuropathic pain syndromes that are rare and relatively unique to the pediatric population. This article discusses the array of neuropathic pain conditions in children and available treatment strategies. Data are limited by small numbers and few randomized controlled trials. Research and clinical implications are discussed.

Neuropathic pain is a difficult to diagnose condition. The definition changes have tried to clarify the confusing consequences about including the word "dysfunction". However, diagnosing problems are not only a definition issue, but also a technical problem. Heat-pulsing-lasers are a very interesting tool to diagnose neuropathic pain, but, at the moment, they are not available in many clinical centers. Because there was not a precise diagnostic tool widely available, a gradation system was developed. It classifies neuropathic pain into three categories: definite, probable or possible neuropathic pain. Neuropathic pain can be produced by different lesions or diseases, either in the central nervous system (CNS) or in the peripheral nervous system (PNS), and it uses to appear in a context of some comorbidities, so it is important to determine the impact over the quality of life and also over the economy (chronic treatment and sick leaves). Some studies have tried to estimate these consequences. Pregabalin has provided throughout different studies important health system cost reductions and also reduced sick leaves. Nevertheless, because only pharmacological-based therapies cannot control disease symptoms and there are still diagnostic problems, it is important to perform a multidisciplinary approach to neuropathic pain to balance these issues. Thus, some studies have investigated different non-pharmacological approaches to treat neuropathic pain, such as intensive exercise, hydrotherapy, transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation, motor imagery programs (MIP), supportive psychotherapy, and cognitive behavior therapy. To perform these non-pharmacological therapies, a multidisciplinary team focused on individualizing pain management is needed., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

Background: A neuropathic component to chronic ischemic pain in peripheral arterial disease (PAD) has recently been shown using quantitative sensory testing (QST) and pain questionnaires. The aim of this study was to examine correlations between QST and pain questionnaires in patients with chronic ischemic pain., Methods: A total of 10 patients with severe PAD (Fontaine stages III and IV) without diabetes mellitus answered a questionnaire and were examined with QST. The questionnaire consisted of several validated instruments which were used to examine the intensity of pain, quality of pain and neuropathic pain (VAS, SF-MPQ, S-LANSS, NPSI)., Results: The results of the QST confirmed previously published data. Several terms of the SF-MPQ showed a correlation with parameters of the QST, such as Allodynia (QST) which correlated with the term tender (SF-MPQ) (Spearman's correlation coefficient 0.911; p< or =0.001) and the NPSI subscore evoked pain correlated with the QST parameter wind-up ratio (0.683; p=0.042)., Conclusion: The results suggest that there might be correlations between psychophysical tests (QST) and pain questionnaires. Subjective perceptions of pain might be represented by a certain pattern in the QST. These connections could contribute to further clarify the pathophysiologic mechanisms leading to the perception of pain.

Objective: Chronic pain is very frequent after spinal cord injury, recent data showing that at least 80% of the patients experience pain, one-third at a severe level. The main objective of the present work is to report and discuss data regarding tools and procedures for the screening, diagnosis, and evaluation of neuropathic pain in spinal cord injury patients., Material and Method: The method used is that developed by the SOFMER, which associated a systematic review of the literature and a selection of published works by a scientific commitee, an analysis of data performed by a binom neuropathic pain/physical medicine and rehabilitation (PM&R) specialists, an evaluation of current practices during an expert consensus conference and via Internet, and finally a validation of the whole work by a pluridisciplinary expert panel., Results: The literature provides an important series of studies on pain in spinal injury, but without specific data about neuropathic pain in this population. Some specific diagnostic and evaluation tools for neuropathic pain have been developed these last years, while numerous classifications, based on various criteria, have been proposed, some of them exhibiting some advantages for a pragmatic application and being in parallel in accordance with recent nosological and physiopathological advances., Discussion: The DN4 questionnaire can be used for the screening and identification of neuropathic pain in this population of patients, often suffering from various types of pain. The use of the Spinal Cord Injury Pain Task Force of the International Association of the Study of Pain classification (SCIP-IASP), although some limitations, is recommended since taking into account physiopathology, localisation, and nature of pain. Daily uses of Visual Analogic Scale (VAS) or Numeric Scale (NS) are an obvious need and that of the questionnaire Douleur de Saint-Antoine (QDSA) for global evaluation and more specifically of the Neuropathic Pain Symptom Inventory (NPSI) for neuropathic pain are highly recommended.

Background and Objective: Different studies have shown pain to be one of the most frequent causes of health-care resource utilization, and a major public health concern because of its social repercussions. In Spain there are no recent data on the prevalence and management of neuropathic pain in the general primary-care setting., Methods: This study aimed to gain epidemiological insight into neuropathic pain in the Spanish primary-care setting. This was a cross-sectional, one-day, multicentre, observational epidemiological study involving 623 primary-care physicians in Spain. Patients who experienced pain were classified into three groups: pure neuropathic pain, mixed neuropathic pain or nociceptive pain. Pain intensity was evaluated on a visual analogue scale (VAS), range 0-10. Information on the location, duration, aetiology and current treatment of pain was obtained, together with data on whether the patients were referred to specialized care and to which type of specialist., Results: In a single day, 23 529 patients received primary care, and of these, 7220 experienced pain (30.7% [95% CI 29.5, 31.7]). Patients with pure neuropathic pain comprised 11.8% (95% CI 10.5, 13.2) of the 3044 patients for whom pain was the reason for consultation and the type of pain was documented, patients with mixed neuropathic pain accounted for 13.4% (95% CI 12.0, 14.8) of this group, and patients with nociceptive pain for 74.9% (95% CI 73.1, 76.7). Patients with pure neuropathic pain mostly received exclusively pharmacological treatment (84.6% [95% CI 80.3, 89.0]), with antiepileptic drugs being the most widely used substances (52.5% [95% CI 47.3, 57.7]), followed by non-opioid analgesics (35.2% [95% CI 30.2, 40.1]) and NSAIDs (26.8% [95% CI 22.2, 31.4]). The mean duration of neuropathic pain was 11.7 +/- 23.3 months. The mean pain intensity on the VAS exceeded 6 in all groups. Over half of the patients were diagnosed in the primary-care centre, and a large proportion in turn were referred to a specialist, most frequently an orthopaedist., Conclusions: The results of the present study show the high prevalence of neuropathic pain at the primary-care level in Spain. In addition, the data presented here point to a need to improve the management of outpatients with neuropathic pain in the Spanish primary-care setting, particularly in relation to the higher than recommended use of NSAIDs (which are not indicated for neuropathic pain) and the lower than recommended use of antiepileptic drugs with an analgesic indication for pain with a neuropathic component.

Objective: Stretch injury to the brachial plexus may occur following traumatic flexion-extension of the cervical spine often seen in motor vehicle accidents or falls. Radiologic and conventional nerve conduction studies are negative in many cases. The present study was undertaken in an attempt to simplify, standardize, and quantify the positive and negative sensory abnormalities that are most often seen during the clinical examination., Methods: Quantitation of thresholds for thermal detection and pain, vibration, pressure pain and elevated arm stress test was performed in a series of 38 patients with the clinical picture of brachial plexus traction injury as well as a group of age and sex matched control subjects., Results: Significant decreases in all evoked pain thresholds, except for heat pain, along with increases in sensory detection thresholds were found in the patient group compared with controls., Discussion: Quantification of sensory findings may greatly facilitate and substantiate the diagnosis of this type of injury. The data are consistent with the hypothesis that brachial plexus traction injury causes dysfunction of small sensory fiber systems and results in a form of neuropathic pain.

Neuropathic pain can be caused by a variety of nerve lesions and it is unsettled whether it should be categorised into distinct clinical subtypes depending on aetiology or type of nerve lesion or individualised as a specific group, based on common symptomatology across aetiologies. In this study, we used a multivariate statistical method (multiple correspondence analyses) to investigate associations between neuropathic positive symptoms (assessed with a specific questionnaire, the Neuropathic Pain Symptom Inventory [NPSI]) and aetiologies, types of nerve lesion and pain localisations. We also examined the internal structure of the NPSI and its relevance to evaluation of symptoms of evoked pains by exploring their relationships with clinician-based quantified measures of allodynia and hyperalgesia. This study included 482 consecutive patients (53% men; mean age: 58+/-15 years) with pain associated with peripheral or central lesions. Factor analysis showed that neuropathic symptoms of the NPSI can be categorised into five dimensions. Spearman correlation coefficients indicated that self-reported pain evoked by brush, pressure and cold stimuli strongly correlated to allodynia/hyperalgesia to brush, von Frey hairs and cold stimuli (p<0.0001, n=90). Multiple correspondence analyses indicated few associations between symptoms (or dimensions) and aetiologies, types of lesions, or pain localisations. Exceptions included idiopathic trigeminal neuralgia and postherpetic neuralgia. We found that there are more similarities than differences in the neuropathic positive symptoms associated with a large variety of peripheral and central lesions, providing rationale for subgrouping aetiologically diverse neuropathic patients into a specific multidimensional category for therapeutic management.

Objective: There is no consensus among experts regarding the etiology or management of patellofemoral pain syndrome (PFPS). Observations indicating dysfunction of the peripheral nervous system around the patellae have been reported. To what extent these sensory abnormalities cause pain has so far not been investigated. The aim of this study was to assess whether a subgroup of patients with unilateral PFPS have neuropathic pain related to the painful knee., Method: A total of 91 patients with unilateral PFPS, between 18 and 40 years of age, and a comparable group of 23 healthy participants aged 18 to 44 years were included. Level of knee function, pain intensity, and qualities were assessed. Somatosensory assessments were carried out by bedside neurologic tests and quantitative sensory testing, assessing thermal, tactile, and vibration thresholds., Results: Ample signs of sensory aberrations with considerable heterogeneity and overlap regarding the degree and type of dysfunction of the nervous system were found in the painful area of the PFPS patients. No clear subgroup of patients with neuropathic pain or clustering of features related to neuropathic pain was identified., Discussion: This study hypothesizes that the observed sensory aberrations may cause neuropathic pain in patients with PFPS. There is no validated method for subgrouping patients with possible neuropathic pain and in this study considerable heterogeneity and overlap regarding signs and symptoms of neuropathic pain made subgrouping even more difficult. A mechanism-based understanding of the pain is, however, essential for the selection of adequate treatment strategies in painful musculoskeletal disorders.

This article highlights the process of making the proper orofacial pain diagnosis. A classification is presented based on the clinical characteristics of the pain complaint and the structure by which it emanates. It is meant to serve as a road map for the clinician, which will help him or her establish the correct diagnosis, thereby allowing the selection of the proper treatment.

Cranial neuralgias are paroxysmal painful disorders of the head characterised by some shared features such as unilaterality of symptoms, transience and recurrence of attacks, superficial and "shock-like" quality of pain and the presence of triggering factors. Although rare, these disorders must be promptly recognised as they harbour a relatively high risk for underlying compressive or inflammatory disease. Nevertheless, misdiagnosis is frequent. Trigeminal and glossopharyngeal neuralgias are sustained in most cases by a neurovascular conflict in the posterior fossa resulting in a hyperexcitability state of the trigeminal circuitry. If the aetiology of trigeminal neuralgia (TN) and other typical neuralgias must be brought back to the peripheral injury, their pathogenesis could involve central allodynic mechanisms, which, in patients with inter-critical pain, also engage the nociceptive neurons at the thalamic-cortical level. Currently available medical treatments for TN and other cranial neuralgias are reviewed.

Pain usually results from activation of nociceptive afferents by actually or 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 "pain 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 affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.

Purpose: We report the treatment of 9 patients with 9 painful neuromas at the tips of the digits using reverse pedicled island flaps containing subcutaneous nerves that were connected to the digital nerve stumps after removal of the neuromas., Methods: There were 9 patients (7 men and 2 women) with painful cutaneous neuromas at the tips of the digits. The ages of the patients at time of surgery were 21 to 66 years (mean, 46 y). All neuromas were formed in the palmar digital nerves in the hand. Preoperative and postoperative status of the patients with neuromas were assessed and graded using a system modified from previously described grading systems for patients with neuromas. Recovery of sensation in the transplanted skin islands was assessed using the Semmes-Weinstein monofilament test., Results: In the preoperative assessment of patients using the grading system for neuromas, 3 patients were assessed as grade 4 (severe), 5 patients as grade 3 (moderate), and the remaining patient as grade 2 (mild). After surgery, Tinel sign disappeared completely in 6 of 9 patients. According to the grading system for neuromas, 6 patients were assessed as grade 1 (normal), and the other 3 patients were assessed as grade 2 (mild) postoperatively. Using the Semmes-Weinstein monofilament test for assessing recovery of sensation of the skin islands, 3 patients recognized the 2.83 monofilament (normal), 2 patients recognized the 3.22 monofilament (loss of tactile sense), and the remaining 4 patients recognized the 3.66 monofilament applied (loss of tactile sense)., Conclusions: This skin island approach provided us with good pain control and recovery of hand function after painful neuromas., Type of Study/level of Evidence: Therapeutic IV.

Background Context: Neurological symptoms are a well-recognized complication after posterior lumbar interbody fusion (PLIF) surgery. Concerns about this potential problem may deter surgeons from performing the procedure., Purpose: To determine the incidence, etiology, prevention, and management of neuralgia after PLIF surgery., Study Design/setting: This study is a retrospective review of patients who underwent PLIF surgery at a university hospital in the north east of England., Patient Sample: Two hundred sixty patients who met the inclusion criteria of degenerative disc disease, spondylolisthesis, disc herniation, and postlaminectomy/postdiscectomy syndrome underwent PLIF surgery., Outcome Measures: The outcome measure of neuralgia was assessed postoperatively by a subjective description of leg pain. Patients were considered to have post PLIF neuralgia if they complained of severe radiculopathy, which was not present before surgery., Methods: During the study period April 1996 to April 2002, all patients who met the inclusion criteria underwent the PLIF procedure. Outcome was assessed postoperatively. In all but the first 20 cases, interbody cages were used. A subtotal superior facetectomy was performed on the first 103 patients. The subsequent 123 patients had a total removal of the superior facet. Autogenous bone and pedicle screws and plates were used in all cases., Results: The study group comprised 226 patients (121 women, 105 men; mean age at surgery, 44.1 years; age range, 12-81 years). Duration of symptoms ranged from 5 to 480 months (mean, 90.6 months; median, 60.0). Overall, there were 16 cases of neuralgia in 226 patients (7.1%). In the subtotal facetectomy group, 10 of the 103 patients (9.7%) had neuralgic symptoms. In the total facetectomy group, 6 of the 123 patients (4.9%) had neuralgic symptoms. The difference in incidence was not statistically significant (p=.158)., Conclusions: This study describes our experiences of post-PLIF neuralgia. It outlines strategies for prevention and management of the problem.

We aimed to locate a chronic pain-associated QTL in the rat (Rattus norvegicus) based on previous findings of a QTL (pain1) on chromosome 15 of the mouse (Mus musculus). The work was based on rat selection lines HA (high autotomy) and LA (low autotomy) which show a contrasting pain phenotype in response to nerve injury in the neuroma model of neuropathic pain. An F(2) segregating population was generated from HA and LA animals. Phenotyped F(2) rats were genotyped on chromosome 7 and chromosome 2, regions that share a partial homology with mouse chromosome 15. Our interval mapping analysis revealed a LOD score value of 3.63 (corresponding to p=0.005 after correcting for multiple testing using permutations) on rat chromosome 2, which is suggestive of the presence of a QTL affecting the predisposition to neuropathic pain. This QTL was mapped to the 14-26cM interval of chromosome 2. Interestingly, this region is syntenic to mouse chromosome 13, rather than to the region of mouse chromosome 15 that contains pain1. This chromosomal position indicates that it is possibly a new QTL, and hence we name it pain2. Further work is needed to replicate and to uncover the underlying gene(s) in both species.

Neuropathic pain, following a lesion of the peripheral or primary nervous system, is characterized by a set of pathophysiologic mechanisms and a clinical expression that distinguishes it from other chronic pain, especially inflammatory pain. These two types of pain are nonetheless frequently found in the same patient. It is important to be able to recognize neuropathic pain, either isolated or associated with other chronic pain, because it requires appropriate management.

Accumulating evidence over last several years indicates an important role of microglial cells in the pathogenesis of neuropathic pain. Signal transduction in microglia under chronic pain states has begun to be revealed. We will review the evidence that p38 MAPK is activated in spinal microglia after nerve injury and contributes importantly to neuropathic pain development and maintenance. We will discuss the upstream mechanisms causing p38 activation in spinal microglia after nerve injury. We will also discuss the downstream mechanisms by which p38 produces inflammatory mediators. Taken together, current data suggest that p38 plays a critical role in microglial signaling under neuropathic pain conditions and represents a valuable therapeutic target for neuropathic pain management.

Background: The state of organized care of neurologic pain patients in Germany was to be established with the the help of our survey., Methods: A five-page questionnaire was sent to 391 neurologic department heads., Results: Nearly 60% of the departments participated in the survey. Almost all neurologic departments admit pain patients, especially for further diagnostics and neurologic treatment. These are accepted as important neurologic tasks. The quality of care is excellent. For the diagnostics of chronic pain, multidimensional questionnaires are used in nearly 64% of the departments and psychometric tests in almost 70%. Sixty percent of all units document the acute course of pain treatment. Follow-up examinations are performed in 26% of all hospitals., Conclusion: Structures exist concerning diagnostics and therapy for neurological in- and outpatients with pain. Care procedures for inpatients with pain need improvement. Outcome is seldom documented.

N-type calcium channels are essential mediators of spinal nociceptive transmission. The core subunit of the N-type channel is encoded by a single gene, and multiple N-type channel isoforms can be generated by alternate splicing. In particular, cell-specific inclusion of an alternatively spliced exon 37a generates a novel form of the N-type channel that is highly enriched in nociceptive neurons and, as we show here, downregulated in a neuropathic pain model. Splice isoform-specific small interfering RNA silencing in vivo reveals that channels containing exon 37a are specifically required for mediating basal thermal nociception and for developing thermal and mechanical hyperalgesia during inflammatory and neuropathic pain. In contrast, both N-type channel isoforms (e37a- and e37b-containing) contribute to tactile neuropathic allodynia. Hence, exon 37a acts as a molecular switch that tailors the channels toward specific roles in pain.

Neuropathic pain can be divided into sympathetically maintained pain (SMP) and sympathetically independent pain (SIP). Rats with tibial and sural nerve transection (TST) produce neuropathic pain behaviors, including spontaneous pain, tactile allodynia, and cold allodynia. The present study was undertaken to examine whether rats with TST would represent SMP- or SIP-dominant neuropathic pain by lumbar surgical sympathectomy. The TST model was generated by transecting the tibial and sural nerves, leaving the common peroneal nerve intact. Animals were divided into the sympathectomy group and the sham group. For the sympathectomy group, the sympathetic chain was removed bilaterally from L2 to L6 one week after nerve transection. The success of the sympathectomy was verified by measuring skin temperature on the hind paw and by infra red thermography. Tactile allodynia was assessed using von Frey filaments, and cold allodynia was assessed using acetone drops. A majority of the rats exhibited withdrawal behaviors in response to tactile and cold stimulations after nerve stimulation. Neither tactile allodynia nor cold allodynia improved after successful sympathectomy, and there were no differences in the threshold of tactile and cold allodynia between the sympathectomy and sham groups. Tactile allodynia and cold allodynia in the neuropathic pain model of TST are not dependent on the sympathetic nervous system, and this model can be used to investigate SIP syndromes.