Capsaicin 8% Patch Repeat Treatment in Nondiabetic Peripheral Neuropathic Pain: A 52-Week, Open-Label, Single-Arm, Safety Study.

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.

Placebo responses in long-standing complex regional pain syndrome: a systematic review and meta-analysis.

UNLABELLED: The typical placebo response (ie, the nonspecific effects in the placebo group including benign natural course, regression to the mean, expectation/conditioning effects, and others) in randomized trials in complex regional pain syndrome (CRPS) is unknown. We recently observed a surprising near-absence of placebo response in a randomized controlled trial we conducted on patients with long-standing (≥6 months) CRPS. To investigate the idea that there may be an absence of placebo response in long-standing CRPS further, we conducted a systematic review and meta-analysis of placebo responses in randomized controlled trials conducted in patients with CRPS of ≥6 months. We systematically identified suitable randomized controlled trials published between 1966 and September 2013. We calculated the mean difference and standard error of the mean difference for placebo responses and synthesized individual effect sizes at 4 specified time periods of interest (15-30 minutes, 1 week, 3-4 weeks, and 6 weeks or more) via meta-analysis using the method of inverse-variance. Heterogeneity was assessed according to the I(2) statistic. For primary analysis, we pooled trial-specific effect sizes over the 4 time points. We analyzed data from 340 participants from 18 trials out of a possible 361 participants from 20 trials (94% of participants analyzed). Significant heterogeneity was present between trials; therefore, we interpreted trends from visual inspection of individual trials and pooled estimates. Placebo response was significant at the earliest time period (15-30 minutes). There was no significant evidence of placebo response at any of the other time periods. These results inform the design of future trials, and they caution against the "therapeutic" use of placebo in long-standing CRPS. PERSPECTIVE: In this meta-analysis of placebo responses in randomized controlled trials in long-standing CRPS, published during 1966 to 2013, we found no evidence for placebo analgesia, except at very early time points. Results inform the design of future placebo analgesia research in long-standing CRPS.

Specific brain morphometric changes in spinal cord injury with and without neuropathic pain.

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.

Ipsilateral cortical activation in fibromyalgia patients during brushing correlates with symptom severity.

OBJECTIVE: To evaluate cortical activation patterns during mechanical-tactile stimulation in fibromyalgia syndrome (FMS) patients and to correlate cortical activation changes with clinical symptoms. METHODS: Nineteen female FMS patients and 18 matched, healthy control subjects underwent EEG examination during brushing stimulation of the right forearm. Participants rated any pain experienced and underwent a manual tender point scale (MTPS) examination. Amplitude changes of cortical rhythms during brushing were analysed in alpha (8-13 Hz) and beta (16-24 Hz) frequency bands. RESULTS: Thirteen patients reported pain during brushing. Independent t-test comparison of event related desynchronisation (ERD) during brushing revealed a cluster of electrodes over ipsilateral (right) central-parietal region which demonstrated ERD in patients only. Clinical MTPS scores correlated with beta-band ERD in this cluster of electrodes. Beamformer analysis revealed a widespread array of source activations in patients, including bilateral insula and primary and secondary somatosensory cortices. Control subject source activations were limited to contralateral (left) hemisphere. CONCLUSIONS: Results indicate ipsilateral cortical activations in FMS patients, but not in healthy controls, during brushing. Ipsilateral ERD during brushing is associated with MTPS score suggesting abnormal processing of somatosensory input which may contribute to clinical pain. SIGNIFICANCE: Altered functioning in FMS may reflect physiological changes in response to afferent somatosensory information manifesting in chronic pain.

Características climáticas y epidemiológicas asociadas al cólico renal en una zona urbana en España / Climate and Epidemiological Characteristics of Renal Colic Attendances in an Urban Setting in Spain

Objetivos: Determinar la incidencia real de los episodios de cólico renal (CR) en nuestro ámbito, así como su relación con varios factores epidemiológicos, estacionales y climáticos. Material y Métodos: Hemos analizado los registros de 156.687 atenciones en el Servicio de Urgencias del Hospital Infanta Cristina (Parla, Madrid, España), desde su apertura el 7 de abril de 2008 hasta la fecha del análisis (28 de marzo de 2010). Se registraron la fecha de nacimiento, el sexo, la historia de episodios previos de CR, el motivo de consulta y la fecha de la atención. Se obtuvieron también los valores diarios de algunos parámetros climáticos (temperatura máxima y humedad relativa). Resultados: Se registraron un total de 1.866 episodios de CR (1,19% de todas las atenciones). La edad osciló entre los 15 y los 94 años, con una mediana de 39. Los episodios de CR fueron más prevalentes en la población masculina (58,4% vs. 41,6% en la femenina, respectivamente, p<0,001). No se observaron diferencias con respecto a la historia previa de CR. Se observó un modesto pero significativo aumento en la incidencia de CR durante las estaciones de verano y otoño. No existió correlación significativa entre el número de atenciones por CR y los parámetros climáticos estudiados. Conclusiones: La incidencia de CR en nuestro ambiente es similar a la existente en la literatura. Se registró un aumento modesto pero significativo de la incidencia durante el verano y otoño, aunque no se observó relación significativa con los valores climáticos de temperatura y humedad. La ausencia de cambios estacionales importantes en la incidencia de CR puede explicarse por las características meteorológicas “no-extremas” del ambiente estudiado (AU)

Objectives: To address the real incidence of RC episodes in our setting and its relationship with several epidemiological, seasonal and climatic factors. Material and Methods: We analyzed 156,687 attendances in the emergency unit of Hospital Infanta Cristina (Parla, Madrid, Spain), from the opening of the unit in 07/04/2008 to the date of analysis (28/03/2010). Date of birth, sex, history of previous urinary lithiasis episodes, main cause and date of attendance were collected. Daily climate parameters (maximum daily temperature and percent relative humidity) were recorded. Results: A total number of 1,866 RC episodes (1.19% of all attendances) were recorded during the study period. Age ranged from 15 to 94 years, median 39. RC episodes were more prevalent in male population (58.4% vs 41.6% in females respectively, p<0.001). No differences were observed with regard to previous history of RC. A modest but significant rise in RC incidence was observed during summer and autumn. No significant correlation was observed between monthly or seasonal number of RC attendances and the climatic parameters studied. Conclusions: RC incidence in our setting is similar to the previously reported in the literature. A modest but significant higher incidence of renal colic episodes were observed during summer and autumn seasons, although no significant relationship was attributed to temperature and humidity values. Absence of dramatic seasonal changes in incidence can be explained by the “non-extreme” weather conditions in the studied setting (AU)

[Climate and epidemiological characteristics of renal colic attendances in an urban setting in Spain]. / Características climáticas y epidemiológicas asociadas al cólico renal en una zona urbana en España.

OBJECTIVES: To address the real incidence of RC episodes in our setting and its relationship with several epidemiological, seasonal and climatic factors. MATERIAL AND METHODS: We analyzed 156,687 attendances in the emergency unit of Hospital Infanta Cristina (Parla, Madrid, Spain), from the opening of the unit in 07/04/2008 to the date of analysis (28/03/2010). Date of birth, sex, history of previous urinary lithiasis episodes, main cause and date of attendance were collected. Daily climate parameters (maximum daily temperature and percent relative humidity) were recorded. RESULTS: A total number of 1,866 RC episodes (1.19% of all attendances) were recorded during the study period. Age ranged from 15 to 94 years, median 39. RC episodes were more prevalent in male population (58.4% vs 41.6% in females respectively, p<0.001). No differences were observed with regard to previous history of RC. A modest but significant rise in RC incidence was observed during summer and autumn. No significant correlation was observed between monthly or seasonal number of RC attendances and the climatic parameters studied. CONCLUSIONS: RC incidence in our setting is similar to the previously reported in the literature. A modest but significant higher incidence of renal colic episodes were observed during summer and autumn seasons, although no significant relationship was attributed to temperature and humidity values. Absence of dramatic seasonal changes in incidence can be explained by the "non-extreme" weather conditions in the studied setting.

Cortical activation changes during repeated laser stimulation: a magnetoencephalographic study.

Repeated warm laser stimuli produce a progressive increase of the sensation of warmth and heat and eventually that of a burning pain. The pain resulting from repetitive warm stimuli is mediated by summated C fibre responses. To shed more light on the cortical changes associated with pain during repeated subnoxious warm stimulation, we analysed magnetoencephalographic (MEG) evoked fields in eleven subjects during application of repetitive warm laser stimuli to the dorsum of the right hand. One set of stimuli encompassed 10 laser pulses occurring at 2.5 s intervals. Parameters of laser stimulation were optimised to elicit a pleasant warm sensation upon a single stimulus with a rise of skin temperature after repeated stimulation not exceeding the threshold of C mechano-heat fibres. Subjects reported a progressive increase of the intensity of heat and burning pain during repeated laser stimulation in spite of only mild (4.8°C) increase of skin temperature from the first stimulus to the tenth stimulus. The mean reaction time, evaluated in six subjects, was 1.33 s, confirming involvement of C fibres. The neuromagnetic fields were modelled by five equivalent source dipoles located in the occipital cortex, cerebellum, posterior cingulate cortex, and left and right operculo-insular cortex. The only component showing statistically significant changes during repetitive laser stimulation was the late component of the contralateral operculo-insular source peaking at 1.05 s after stimulus onset. The amplitude increases of the late component of the contralateral operculo-insular source dipole correlated with the subjects' numerical ratings of warmth and pain. Results point to a pivotal role of the contralateral operculo-insular region in processing of C-fibre mediated pain during repeated subnoxious laser stimulation.

NeuPSIG guidelines on neuropathic pain assessment.

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.

Multiple sclerosis-related central pain disorders.

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.

The long-term outcome of microvascular decompression for trigeminal neuralgia.

OBJECTIVE: Evaluation of the effectiveness of Microvascular Decompression (MVD) for Trigeminal Neuralgia (TGN), with emphasis on patient's perception of outcome, and satisfaction with the procedure. MATERIALS AND METHODS: A cohort of 372 MVD operations carried out between 1982 and 2005 were reviewed, contact could be attempted with 319 patients. Questionnaires assessing the patient's perception of outcome returned by 266 patients (71%). statistical analysis of the data was carried out using a cox proportional-hazard regression analysis. Anticipated outcome measures: Time to pain recurrence; predictive value of imaging, operative findings and complications; patients' satisfaction, and outcome of revision MVD. RESULTS: Complete pain relief (off medication) achieved in 71% of patients at 10 years. Overall 84% of responders to questionnaires expressed satisfaction with the operative outcome, the mean duration of TGN was 80 months and mean post-operative follow-up of 7 years. No mortality reported in this series. CONCLUSION: This is a large review of MVD, which confirms the long-term effectiveness of the procedure, and uniquely reflects patient's perception of the operation. Predictors of favourable outcome were shorter preoperative duration of TGN, older age at time of MVD, typical features, and vascular compression; moreover, complications, and previous neurodestructive procedures did not show significant effect on long-term pain relief. Satisfaction with MVD was exclusively related to long-term pain relief without medications.

1. Trigeminal neuralgia.

Trigeminal neuralgia is a common cause of facial pain. It has a significant impact on the quality of life and the socioeconomic functioning of the patient. The aim of this review is to provide recommendations for medical management of trigeminal neuralgia based on current evidence. Based upon the analyses of the literature combined with experience in pain management, symptoms, assessment, differential diagnosis, and treatment possibilities of trigeminal neuralgia are described and discussed. Recommendations for pain management are given and are displayed in a clinical practice algorithm. Treatment should be multidisciplinary. Various treatment options and their risks should be discussed with the patient. The first treatment of choice is carbamazepine or oxcarbazepine. In younger patients, the first choice of invasive treatment is probably microvascular decompression. For elderly patients, radiofrequency treatment of Gasserian ganglion is recommended and the technique is described in detail.

Development and preliminary validation of the NePIQoL: a quality-of-life measure for neuropathic 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.

Alpha adrenoceptor agonist-induced microcirculatory oscillations are reduced in diabetic neuropathy.

In diabetic patients small fiber neuropathy has been associated with impairment of 0.1 Hz microvascular vasomotion. The aim of this study was (1) to investigate whether vasoconstriction-induced microvascular oscillations in the skin are reduced in diabetic patients with peripheral and/or autonomic neuropathy, and (2) whether this method could be used as a non-invasive surrogate marker to assess diabetic small fiber neuropathy. Four matched groups were studied: diabetic patients without neuropathy (D), with peripheral neuropathy (DPN), with peripheral and autonomic neuropathy (DAN), and non-diabetic controls (Ctrl). All participants were evaluated for peripheral and autonomic neuropathy, microvascular endothelial function, and metabolic syndrome indicators. Laser Doppler flowmetry was used to measure oscillations after iontophoresis of the alpha one selective agonist phenylephrine. approximately 0.1-Hz oscillations recorded at the foot were significantly attenuated in diabetic patients with peripheral and/or autonomic neuropathy (DPN and DAN groups) compared to diabetic patients without neuropathy or non-diabetic controls. In the forearm, microvascular oscillations were significantly reduced only in patients with autonomic neuropathy (DAN). Oscillation measures correlated significantly (P<0.001) with all markers of peripheral neuropathy but not with markers of measurements of microvascular endothelial function, or metabolic syndrome markers. In a logistic regression model, reduced microvascular oscillations at the foot were a strong predictor for the presence of peripheral neuropathy. The measurement of phenylephrine-induced approxiamtely 0.1-Hz microvascular oscillation may represent a useful non-invasive tool with which to study the effects of treatment strategies on the diabetic small fiber neuropathy.

Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.

BACKGROUND: Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS. OBJECTIVE: The purpose of this extension was to establish long-term tolerability and effectiveness profiles for THC/CBD (Sativex (R), GW Pharmaceuticals plc, Salisbury, United Kingdom) oromucosal spray in CNP associated with MS. METHODS: This uncontrolled, open-label trial was an indefinite-duration extension of a previously reported 5-week randomized study in patients with MS and CNP. In the initial trial, patients were randomized to placebo or THC/CBD. Patients were only required to maintain their existing analgesia in the randomized study. In the open-label trial they could vary their other analgesia as required. All patients (placebo and THC/CBD) who completed the randomized trial commenced the open-label follow-up on THC/CBD (27 mg/mL: 25 mg/mL). Patients titrated their dosage, maintaining their existing analgesia. The primary end point of the trial was the number, frequency, and type of adverse events (AEs) reported by patients. Secondary end points included changes from baseline in 11-point numerical rating scale (NRS-11) neuropathic pain score, hematology and clinical chemistry test results, vital signs, trial drug usage, and intoxication visual analogue scale scores. RESULTS: Sixty-six patients were enrolled in the randomized trial; 64 (97%) completed the randomized trial and 63 (95%) entered the open-label extension (race, white, 100%; sex, male, 14 [22%]; mean [SD] age, 49 [8.4] years [range, 27-71 years[). The mean (SD) duration of open-label treatment was 463 (378) days (median, 638 days; range, 3-917 days), with 34 (54%) patients completing >1 year of treatment with THC/CBD and 28 (44%) patients completing the open-label trial with a mean (SD) duration of treatment of 839 (42) days (median, 845 days; range, 701-917 days). Mean NRS-11 pain scores in the final week of the randomized trial were 3.8 in the treatment group and 5.0 in the placebo group. In the 28 (44%) patients who completed the 2-year follow up, the mean (SD) NRS-11 pain score in the final week of treatment was 2.9 (2.0) (range, 0-8.0). Fifty-eight (92%) patients experienced > or =1 treatment-related AE. These AEs were rated by the investigator as mild in 47 (75%) patients, moderate in 49 (78%), and severe in 32 (51%). The most commonly reported AEs were dizziness (27%), nausea (18 %), and feeling intoxicated (11%). Two treatment-related serious AEs (ventricular bigeminy and circulatory collapse) were judged to be treatment-related. Both serious AEs occurred in the same patient and resolved completely following a period of discontinuation. Eleven (17%) patients experienced oral discomfort, 4 persistently. Regular oral examinations revealed that 7 (11%) patients developed white buccal mucosal patches and 2 (3%) developed red buccal mucosal patches; all cases were deemed mild and resolved. Seventeen (25%) patients withdrew due to AEs. The mean number of sprays and patients experiencing intoxication remained stable throughout the follow-up trial. CONCLUSIONS: THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment (n = 28). Ninety-two percent of patients experienced an AE, the most common of which were dizziness and nausea. The majority of AEs were deemed to be of mild to moderate severity by the investigators.

Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial.

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.

Pharmacologic management of neuropathic pain: evidence-based recommendations.

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.

Validation and reliability of the Neuropathic Pain Scale (NPS) in multiple sclerosis.

OBJECTIVE: Central neuropathic pain occurs in around 28% of patients with multiple sclerosis (MS). The Neuropathic Pain Scale (NPS) has received preliminary validation in peripheral neuropathic pain conditions. The aim of this study was to validate its use in MS central pain syndromes. METHODS: We administered the NPS to 141 patients with MS, together with the Short Form McGill Pain Questionnaire (SFMPQ), the Hospital Anxiety and Depression Scale (HADS), and Short Form 36 Health Survey (SF-36). RESULTS: Cronbach's alpha was 0.78 (95% CI 0.69; 0.83), implying a high degree of internal consistency. Three factors, "Familiar," "Superficial," and "Alien Perception," were extracted, accounting for 64% of the variance. The NPS 10-item total correlates with: the SFMPQ 15-item total score, rho=0.63 (95% CI 0.49; 0.74), its Visual Analog Scale, rho=0.49 (95% CI 0.33; 0.64), the transformed Pain domain of the SF-36 rho=-0.49 (95% CI -0.63; -0.32), but not with its remaining seven health domains, or with either the HADS anxiety or the depression scores. Limits of agreement for short-term test or re-test reliability of the 100 point NPS total (median 2 days, range 1 to 7) were -12 to 14 and when administered to 78 patients who rated their neuropathic pain the "Same" [median interval 33 days (range 19 to 126), the long-term test or re-test correlation coefficient was 0.71 (95% CI 0.6; 0.79)]. DISCUSSION: The NPS appears a useful tool in the assessment of neuropathic pain in MS patients and possibly in measuring outcomes of therapeutic interventions.

Recommendations for the management of herpes zoster.

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.