Assessment of pain quality in chronic neuropathic and nociceptive pain clinical trials with the Neuropathic Pain Scale.

Although a number of measures of pain qualities exist, little research has examined the potential for these measures to identify the unique effects of pain treatments on different pain qualities. We examined the utility of the Neuropathic Pain Scale (NPS) for assessing changes in pain qualities after open label lidocaine patch 5% in 3 samples of patients: patients with peripheral neuropathic pain, low back pain, and osteoarthritis. With one exception ("cold" pain in subjects with low back pain), each of the NPS items showed significant change after open label lidocaine patch. In addition, significantly larger changes were observed for the NPS items reflecting global pain intensity and pain unpleasantness and for items assessing sharp and deep pain than for items assessing cold, sensitive, and itchy pain. The pattern of changes in pain qualities did not differ across the 3 diagnostic groups, but it did differ from the patterns of changes in pain qualities associated with other analgesic treatments. The results support the potential utility of the NPS for assessing the patterns of changes in pain qualities that can be observed after pain treatment. PERSPECTIVE: Pain clinical trials that include measures of pain qualities, such as the NPS, might identify distinct patterns of treatment effects on those pain qualities. This research might be used to help clinicians target analgesics to match the specific qualities associated with a patient's pain and to better understand the mechanisms of analgesic effects in drug development programs.     

The validity of the neuropathic pain scale for assessing diabetic neuropathic pain in a clinical trial

OBJECTIVES: In controlled trials of analgesics for the treatment of neuropathic pain, the primary outcome variable is most often a measure of global pain intensity. However, because neuropathic pain is associated with a variety of pain sensations, the effects of analgesic treatments on different sensations could go undetected if specific pain qualities are not assessed. This study sought to evaluate the utility of assessing the multiple components of neuropathic pain in an analgesic clinical trial. METHODS: One hundred fifty-nine subjects with diabetes-related foot pain were randomly assigned to receive an active analgesic (controlled-release oxycodone) or matching placebo for 6 weeks. A multidimensional measure of neuropathic pain, the Neuropathic Pain Scale (NPS), was administered before, during, and after study treatment. RESULTS: Relative to placebo, the opioid analgesic produced statistically significantly greater decreases in global pain intensity, pain unpleasantness, and sharp, dull, and deep pain sensations. Responder analyses indicated a higher rate of responding to the opioid condition, relative to placebo, for intense, unpleasant, deep, and surface pain. The opioid analgesic did not significantly reduce hot, cold, itchy, or sensitive pain sensations compared with placebo in either analysis. CONCLUSIONS: These findings support the utility of the NPS for characterizing the multidimensional nature of the neuropathic pain experience and for detecting changes in neuropathic pain with treatment.     

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.     

Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study

OBJECTIVE: Our goal was to perform a pilot study to assess the effectiveness and tolerability of a topical lidocaine patch (Lidoderm) for the treatment of peripheral neuropathic pain conditions other than postherpetic neuralgia. DESIGN: This was an open-label prospective study. PATIENTS: Sixteen patients with refractory peripheral neuropathic pain conditions who had reported intolerable side effects or inadequate pain relief with antidepressant, anticonvulsant, antiarrhythmic, and opioid medications participated in this study. Diagnoses included postthoracotomy pain, stump neuroma pain, intercostal neuralgia, diabetic polyneuropathy, meralgia paresthetica, complex regional pain syndrome, radiculopathy, and postmastectomy pain. OUTCOME MEASURES: A six-item Pain Relief Scale was used (0 = worse pain, 1 = no change, 2 = slight relief, 3 = moderate relief, 4 = a lot of relief, 5 = complete relief). RESULTS: Moderate or better pain relief was reported by 13 of the 16 participants (81%). One patient stopped treatment after 4 days due to lack of relief. The remaining 15 patients had a mean duration of patch use of 6.2 weeks with continued relief. Only 1 patient reported a side effect, a mild skin irritation. CONCLUSIONS: The Lidoderm patch provided clinically meaningful pain relief in most of these refractory neuropathic pain patients without side effects. Controlled trials need to be performed to confirm these preliminary findings.     

Physiopathology of neuropathic pain syndromes

This article reviews the peripheral and central mechanisms of neuropathic pain. The main mechanisms involved in neuropathic pain are: (1) ectopic activities, (2) ephapses, (3) sensitization of nociceptors. Central morphological alterations could also be involved: (1) medullar neuronal reorganization, (2) hyperexcitability of central nervous system nociceptive neurones. The relative resistance of these neuropathic pains to opioid drugs could be related to a decrease in the number of opioid receptors to an amino acid mediator related spinal neurons hyperexitability and to an increase in non opioid peptides such as cholecystokinin.     

Symptom profiles differ in patients with neuropathic versus non-neuropathic pain.

The distinction between neuropathic and non-neuropathic pain reflects partially distinct mechanisms and patterns of treatment response. It was therefore hypothesized that patients with neuropathic and non-neuropathic pain have different profiles of symptoms and signs. To test this hypothesis, pain intensity, unpleasantness, quality, and spatial characteristics were examined in 618 patients with 1 of 3 peripheral neuropathic pain conditions (painful diabetic peripheral neuropathy, painful idiopathic sensory polyneuropathy, or postherpetic neuralgia), osteoarthritis pain, or low back pain. These assessments were conducted before treatment had begun in clinical trials of lidocaine patch 5% administered alone or with stable dosages of other analgesics. Patients with osteoarthritis pain and low back pain did not differ in their profile of pain quality and spatial characteristics and were combined to form a group of patients with non-neuropathic pain. In univariate analyses, patients with peripheral neuropathic pain reported significantly more intense hot, cold, sensitive, itchy, and surface pain and significantly less intense dull and deep pain than patients with non-neuropathic pain. In a multivariate analysis, the overall pattern of pain quality and spatial characteristics differed significantly between patients with neuropathic and non-neuropathic pain. In addition, specific pain quality and spatial characteristics improved the discrimination of patients with neuropathic and non-neuropathic pain in a logistic regression model that adjusted for demographic covariates and overall pain intensity and unpleasantness. PERSPECTIVE: The results indicate that the distinction between neuropathic and non-neuropathic pain is reflected in different profiles of pain quality and spatial characteristics and suggest that the assessment of patterns of pain symptoms might contribute to the identification of distinct pathophysiologic mechanisms and the development of mechanism-based treatment approaches.     

Pregabalin for peripheral neuropathic pain: results of a multicenter, non-comparative, open-label study in Indian patients

The aim of this study was to evaluate the tolerability, safety and efficacy of pregabalin in Indian patients with peripheral neuropathic pain. In this prospective, multicenter, non-comparative, open-label study, patients with peripheral neuropathic pain (n = 111) received pregabalin in doses ranging from 75 to 300 mg twice daily for 3 weeks. Primary efficacy measures included weekly pain score and the Visual Analogue Scale (VAS) score of the Short-Form McGill Pain Questionnaire (SF-MPQ). Despite a short study duration, a significant reduction was seen in weekly pain score (p < 0.0001), as well as VAS score of SF-MPQ (p < 0.0001). Significant improvements were also seen in other pain-related endpoints, weekly sleep interference score, quality of life measures, and patient and clinician ratings of global improvement. Pregabalin was well tolerated, and the most common adverse events were dizziness and somnolence. The short study duration precluded the assessment of longer term safety issues such as weight gain. This study has demonstrated the safety, tolerability and efficacy of pregabalin for peripheral neuropathic pain in Indian patients.     

A prospective,open‐label,multicentre study of pregabalin in the treatment of neuropathic pain in Latin America

Aims: The objective of this study was to evaluate the safety and efficacy of pregabalin at flexible doses of 150–600 mg/day in Latin American patients with neuropathic pain. Methods: A prospective, multicentre, open‐label, non‐comparative study included patients age ≥ 18 years diagnosed with neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, chemotherapy‐induced peripheral neuropathic pain (PNP), or human immunodeficiency virus‐related PNP. Eligible patients (N = 121) had a score of ≥ 40 mm on the visual analogue scale and a daily pain rating scale (DPRS) score of ≥ 4 throughout screening. Patients received flexible‐dose pregabalin (150–600 mg/day) for 12 weeks, which included a 4‐week dose‐adjustment phase. The primary efficacy measure was change from baseline to end of treatment/last observation carried forward (EOT/LOCF) in weekly mean pain score on the DPRS. Secondary efficacy measures included pain, anxiety, sleep interference, treatment satisfaction and Patient and Clinician Global Impression of Change. Results: Pregabalin significantly reduced the weekly mean pain score on DPRS from baseline to EOT/LOCF [–3.8 (95% CI: ?4.2 to ?3.3); p < 0.0001]. Reductions from baseline to EOT/LOCF were observed for all secondary efficacy outcomes (p < 0.0001). Pain and sleep interference were significantly improved compared with baseline across all weeks of the study, as early as 1 week after initiation of pregabalin (p < 0.0001). The most common adverse events (AEs) were somnolence, dizziness, weight gain and peripheral oedema. Nine (7.4%) patients discontinued the study because of AEs and 25 (20.7%) temporarily stopped or reduced their pregabalin dose because of AEs. Conclusions: Flexible‐dose pregabalin (150–600 mg/day) significantly reduced pain and anxiety and improved sleep and was generally well tolerated in Latin American patients with neuropathic pain.     

The clinical challenge of chronic neuropathic pain

Background. The clinician often faces the problem that certain types of chronic pains remain refractory to the commonly used analgesic treatment options. Neuropathic pain, which is defined as pain caused by direct nerve lesions, may have different causes and a variety of clinical presentations. A correct management of chronic neuropathic pain requires a thorough understanding of the potential causes, the diagnosis and the pathophysiological mechanisms.

Objectives. The purpose of this review article is to provide the reader with the latest insights in the diagnostic work-out and the clinical presentation of neuropathic pain. Additionally, the possible pathophysiological changes induced by nerve lesions are explained.

Methods. An extensive literature review was performed using Pubmed citations.

Results and conclusions. This article, which is based on extensive literature review, aims at providing a concise review of the current knowledge regarding aetiology, diagnosis and pathophysiology of neuropathic pain.     

The clinical challenge of chronic neuropathic pain

Background.?The clinician often faces the problem that certain types of chronic pains remain refractory to the commonly used analgesic treatment options. Neuropathic pain, which is defined as pain caused by direct nerve lesions, may have different causes and a variety of clinical presentations. A correct management of chronic neuropathic pain requires a thorough understanding of the potential causes, the diagnosis and the pathophysiological mechanisms.

Objectives.?The purpose of this review article is to provide the reader with the latest insights in the diagnostic work-out and the clinical presentation of neuropathic pain. Additionally, the possible pathophysiological changes induced by nerve lesions are explained.

Methods.?An extensive literature review was performed using Pubmed citations.

Results and conclusions.?This article, which is based on extensive literature review, aims at providing a concise review of the current knowledge regarding aetiology, diagnosis and pathophysiology of neuropathic pain.     

A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain.

The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use "medical marijuana," and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PERSPECTIVE: This study adds to a growing body of evidence that cannabis may be effective at ameliorating neuropathic pain, and may be an alternative for patients who do not respond to, or cannot tolerate, other drugs. However, the use of marijuana as medicine may be limited by its method of administration (smoking) and modest acute cognitive effects, particularly at higher doses.     

The S-LANSS score for identifying pain of predominantly neuropathic origin: validation for use in clinical and postal research.

This article describes the development and validation of the S-LANSS score, a self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. The S-LANSS aims to identify pain of predominantly neuropathic origin, as distinct from nociceptive pain, without the need for clinical examination. Two hundred patients with chronic pain were asked to complete the S-LANSS unaided. A researcher then administered the S-LANSS scale and the Neuropathic Pain Scale (NPS) in interview format. An independent clinician determined the pain type (neuropathic versus nociceptive) and rated his or her certainty about diagnosis. The S-LANSS scale was also incorporated into a chronic pain questionnaire that was sent to 160 community patients and 150 newly referred patients waiting for pain clinic assessment. The S-LANSS scale correctly identified 75% of pain types when self-completed and 80% when used in interview format. Sensitivity for self-completed S-LANSS scores ranged from 74% to 78%, depending on the cutoff score. There were significant associations between NPS items and total score with S-LANSS score. In the postal survey, completed questionnaires were returned by 57% of patients (n = 174). Internal consistency and convergent validity of the survey S-LANSS scores were confirmed. The findings support the S-LANSS scale as a valid and reliable self-report instrument for identifying neuropathic pain and it is also acceptable for use in postal survey research. Establishing valid measures of symptoms and signs in neuropathic pain will allow standardized comparisons with other investigational measures. This might lead to new insights into the relationship between pathophysiologic mechanisms and clinical manifestations of pain.