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Background: Dynamic Mechanical Allodynia (DMA) is a typical symptom of neuropathic pain (NP). In a recent study, the capsaicin 8% patch was noninferior to pregabalin in overall peripheral NP relief. In this study, we report the comparison of the two treatments in relieving DMA., Methods: In a randomized, open-label, head-to-head, 8-week study, 488 patients with peripheral NP were treated with the capsaicin 8% patch (one application) or an optimized dose of pregabalin. Assessments included the area and intensity of DMA, and the number of patients achieving complete resolution of DMA., Results: At baseline, 253 patients in the capsaicin 8% patch group and 235 patients in the pregabalin group had DMA. From baseline to end of study, the change in DMA intensity was significantly in favour of the capsaicin 8% patch versus pregabalin [-0.63 (95% CI: -1.04, -0.23; p = 0.002)]. Similarly, the capsaicin 8% patch was superior to pregabalin in reducing the area of DMA [-39.5 cm 2 (95% CI: -69.1, -10.0; p = 0.009)] from baseline to end of study. Overall, a greater proportion of patients had a complete resolution of allodynia with capsaicin 8% patch treatment compared with pregabalin treatment (24.1% vs. 12.3%; p = 0.001) at end of study., Conclusion: Capsaicin 8% treatment was superior to pregabalin in reducing the intensity and area of DMA, and in the number of patients with complete resolution of DMA., Significance: The superiority of a topical treatment over pregabalin in relieving DMA supports the view that both peripheral and central sensitization can mediate allodynia., (© 2017 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Objectives: To investigate the long-term safety and tolerability of capsaicin 8% patch repeat treatment in nondiabetic patients with peripheral neuropathic pain., Methods: A prospective, open-label, observational study in patients with postherpetic neuralgia, posttraumatic or postsurgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral neuropathic pain, and average daily pain score ≥4, who received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9 to 12 wk intervals). Sensory testing and analgesic effectiveness were assessed using "bedside tests" and Brief Pain Inventory (question 5)., Results: Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least 2 sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least 1 modality in 50.4% (n=140); deterioration/loss in 1, 2, 3, 4, or 5 modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7), and 1.4% (n=4) cases. Newly emergent hyperesthesia or allodynia was apparent in 1.1% to 3.6% of the cases (depending on modality) by EoS. Between 25.2% and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and month 12., Conclusions: Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.

Background: Clinical trials have not yet compared the efficacy of capsaicin 8% patch with current standard therapy in peripheral neuropathic pain (PNP)., Objectives: Head-to-head efficacy and safety trial comparing the capsaicin patch with pregabalin in PNP., Methods: Open-label, randomized, multicentre, non-inferiority trial. Patients with PNP, aged 18-80 years, were randomly assigned to either the capsaicin 8% patch (n = 282) or an optimised dose of oral pregabalin (n = 277), and assessed for a ≥30% mean decrease in Numeric Pain Rating Scale (NPRS) score from baseline to Week 8. Secondary endpoints included optimal therapeutic effect (OTE), time-to-onset of pain relief and treatment satisfaction., Results: The capsaicin 8% patch was non-inferior to pregabalin in achievement of a ≥30% mean decrease in NPRS score from baseline to Week 8 (55.7% vs. 54.5%, respectively; Odds ratio: 1.03 [95% CI: 0.72, 1.50]). The proportion of patients achieving OTE at Week 8 was 52.1% for the capsaicin 8% patch versus 44.8% for pregabalin (difference: 7.3%; 95% CI: -0.9%, 15.6%). The median time-to-onset of pain relief was significantly shorter for capsaicin 8% patch versus pregabalin (7.5 vs. 36.0 days; Hazard ratio: 1.68 [95% CI: 1.35, 2.08]; p < 0.0001). Treatment satisfaction was also significantly greater with the capsaicin 8% patch versus pregabalin. TEAEs were mild-to-moderate in severity, and resulted in treatment discontinuation only with pregabalin (n = 24). Systemic adverse drug reactions ranged from 0 to 1.1% with capsaicin 8% patch and 2.5 to 18.4% with pregabalin., Conclusions: The capsaicin 8% patch provided non-inferior pain relief to an optimized dose of pregabalin in PNP, with a faster onset of action, fewer systemic side effects and greater treatment satisfaction., (© 2015 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.)

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

This is a revision of guidelines, originally published in 2004, for the assessment of patients with neuropathic pain. Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at peripheral or central level. Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes. Clinical examination, including accurate sensory examination, is the basis of neuropathic pain diagnosis. For more accurate sensory profiling, quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes. Measurement of trigeminal reflexes mediated by A-beta fibers can be used to differentiate symptomatic trigeminal neuralgia from classical trigeminal neuralgia. Measurement of laser-evoked potentials is useful for assessing function of the A-delta fiber pathways in patients with neuropathic pain. Functional brain imaging is not currently useful for individual patients in clinical practice, but is an interesting research tool. Skin biopsy to measure the intraepidermal nerve fiber density should be performed in patients with clinical signs of small fiber dysfunction. The intensity of pain and treatment effect (both in clinic and trials) should be assessed with numerical rating scale or visual analog scale. For future neuropathic pain trials, pain relief scales, patient and clinician global impression of change, the proportion of responders (50% and 30% pain relief), validated neuropathic pain quality measures and assessment of sleep, mood, functional capacity and quality of life are recommended., (Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Central neuropathic pain is common in multiple sclerosis (MS), and its prevalence increases with physical disability. Sufficient evidence links dysesthetic pain, trigeminal neuralgia, Lhermitte's sign, and painful tonics spasms to plaque formation in the spinal cord and brain, whereas the association with headache and back pain remains unclear. Management varies according to the pain in question. For dysesthetic pain, drugs in use for neuropathic pain in general are recommended as first-line treatment, and emerging evidence suggests some benefit from cannabinoids and levetiracetam. Because of unique characteristics of MS-related trigeminal neuralgia, ganglion and root level neuroablative procedures are worth considering before microvascular decompression. Overall, the lack of controlled clinical trials, together with our limited understanding of the pathophysiological mechanisms involved, form a hindrance to a systematic and rational management of MS-related pain.

Neuropathic pain is frequently associated with negative effects on quality of life (QoL), affecting physical, social, and psychological functioning. Of many existing scales used to measure QoL, none have been validated in a neuropathic pain patient population. This study reports on the development and preliminary psychometric evaluation of the Neuropathic Pain Impact on Quality-of-Life questionnaire (NePIQoL), a measure to assess QoL in neuropathic pain. In Phase I, focus groups with 27 patients and a panel of experts identified QoL issues for inclusion in the measure. Initial items (152) and response categories were pretested using cognitive interviewing (18 patients). Following this, the number of items was reduced to 91. In Phase II, the 91-item version of the NePIQoL was administered to a further 112 patients, poorly performing items were identified, and internal consistency was examined. In Phase III, the revised NePIQoL was administered to a further 110 patients on two occasions to examine validity and test-retest reliability. Qualitative and quantitative pretesting led to extensive revision, resulting in a final measure of 42 items. Finally, Phase IV tested the concurrent validity and responsiveness of the NePIQoL. The authors conclude that the NePIQoL is an acceptable, patient-derived, neuropathic pain-specific measure with evidence of reliability, validity, and temporal stability.

Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores -1.48 points vs. -0.52 points on a 0-10 Numerical Rating Scale (p=0.004; 95% CI: -1.59, -0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient's Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks.

Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered for recommendation if their efficacy was supported by at least one methodologically-sound, randomized clinical trial (RCT) demonstrating superiority to placebo or a relevant comparison treatment. Recommendations were based on the amount and consistency of evidence, degree of efficacy, safety, and clinical experience of the authors. Available RCTs typically evaluated chronic NP of moderate to severe intensity. Recommended first-line treatments include certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel alpha2-delta ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second-line treatments in some circumstances include certain antiepileptic and antidepressant medications, mexiletine, N-methyl-D-aspartate receptor antagonists, and topical capsaicin. Medication selection should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs examining treatment of central NP are lacking and should be a priority for future research.

Background: Postherpetic neuralgia (PHN) is a complication of acute herpes zoster, which is emerging as a preferred clinical trial model for chronic neuropathic pain. Although there are published meta-analyses of analgesic therapy in PHN, and neuropathic pain in general, the evidence base has been substantially enhanced by the recent publication of several major trials. Therefore, we have conducted a systematic review and meta-analysis for both efficacy and adverse events of analgesic therapy for PHN., Methods and Findings: We systematically searched databases (MEDLINE 1966-2004, EMBASE 1988-2004, CINAHL 1982-2002, and PubMed [29 October 2004]) for trials of PHN. We also searched references of retrieved studies and review articles for further trials. We included trials that examined adult patients with PHN of greater duration than 3 mo, that were blinded, randomised, and had at least one measure of pain outcome. Dichotomous pain outcome data were extracted for 50% decrease in baseline pain using a hierarchy of pain/pain-relief measurement tools. Where available, dichotomous data were also collected for adverse events. Calculated estimates of efficacy included relative benefit and number needed to treat. Of 62 studies identified, 35 were randomised controlled trials. Of these, 31 were placebo controlled and suitable for meta-analysis, from which it was possible to extract dichotomous efficacy outcome data from 25. This meta-analysis revealed that there is evidence to support the use of the following orally administered therapies: tricyclic antidepressants, "strong" opioids, gabapentin, tramadol, and pregabalin. Topical therapies associated with efficacy were lidocaine 5% patch and capsaicin. Finally, a single study of spinal intrathecal administration of lidocaine and methyl prednisolone demonstrated efficacy, although this has yet to be replicated. Data suggest that the following therapies are not associated with efficacy in PHN: certain NMDA receptor antagonists (e.g., oral memantine, oral dextromethorphan, intravenous ketamine), codeine, ibuprofen, lorazepam, certain 5HT1 receptor agonists, and acyclovir. Topical administration of benzydamine, diclofenac/diethyl ether, and vincristine (iontophoresis) are similarly not associated with efficacy, nor are intrathecal administration of lidocaine alone or epidural administration of lidocaine and methylprednisolone, intravenous therapy with lidocaine, subcutaneous injection of Cronassial, or acupuncture. However, many of the trials that demonstrated a lack of efficacy represented comparatively low numbers of patient episodes or were single-dose studies, so it may be appropriate to regard such interventions as "not yet adequately tested" rather than demonstrating "no evidence of efficacy." Topical aspirin/diethyl ether has not been adequately tested., Conclusion: The evidence base supports the oral use of tricyclic antidepressants, certain opioids, and gabapentinoids in PHN. Topical therapy with lidocaine patches and capsaicin is similarly supported. Intrathecal administration of methylprednisolone appears to be associated with high efficacy, but its safety requires further evaluation.