An epidemiological study of neuropathic pain symptoms in Canadian adults

The reported prevalence of neuropathic pain ranges from 6.9% to 10%; however the only Canadian study reported 17.9%. The objective of this study was to describe the epidemiology of neuropathic pain in Canada. A cross-sectional survey was conducted in a random sample of Canadian adults. The response rate was 21.1% (1504/7134). Likely or possible neuropathic pain was defined using a neuropathic pain-related diagnosis and a positive outcome on the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs pain scale (S-LANSS) or the Douleur Neuropathique 4 (DN4) Questions. The prevalence of likely neuropathic pain was 1.9% (S-LANSS) and 3.4% (DN4) and that of possible neuropathic pain was 5.8% (S-LANSS) and 8.1% (DN4). Neuropathic pain was highest in economically disadvantaged males. There is a significant burden of neuropathic pain in Canada. The low response rate and a slightly older and less educated sample than the Canadian population may have led to an overestimate of neuropathic pain. Population prevalence varies by screening tool used, indicating more work is needed to develop reliable measures. Population level screening targeted towards high risk groups should improve the sensitivity and specificity of screening, while clinical examination of those with positive screening results will further refine the estimate of prevalence

Managing the symptoms of neuropathic pain: An exploration of patients' experiences

The debilitating effects of chronic neuropathic pain on everyday life are considerable but little is known about how individual sufferers manage these effects. Virtually nothing is known about what patients prefer, what measures they take themselves, when, or in what combinations. The aim of this study was to explore patients’ reports of how they managed their neuropathic pain symptoms. Three focus groups including 10 participants were used to generate qualitative data on both individual and shared experiences of managing their symptoms of neuropathic pain. Discussions were recorded and transcribed verbatim. Data were analysed using thematic analysis, identifying categories and broader themes of importance to patients. The most common management strategy was the use of conventional medications, often associated with poor effectiveness and unpleasant side-effects. Complementary and alternative medicine was ineffective but many found resting or retreating helpful. They exhibited a repeated cycle of seeking help to manage the pain, with each unsuccessful attempt followed by new attempts. Some had tried to accept their pain, but there was insufficient psychological, social, emotional and practical support to allow them to do this successfully. This exploratory study provides a basis from which to develop a larger study to validate and extend the findings. Other issues meriting research are the effectiveness of cognitive behavioural therapies for those with neuropathic pain; and an exploration and subsequent evaluation of different types of social, practical and emotional support needed to help live with neuropathic pain

Neuropathic pain clinical trials:factors associated with decreases in estimated drug efficacy

Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. This study is a secondary analysis of data from a previous published NeuPSIG systematic review and meta-analysis, updated to include studies published up till March 2017. We included double-blind, randomized, placebo-controlled trials examining the effect of drugs for which we had made strong or weak recommendations for use in neuropathic pain in the previously published review. As the primary outcome, we used an aggregated number needed to treat for 50% pain reduction (alternatively 30% pain reduction or moderate pain relief). Analyses involved 128 trials. Number needed to treat values increased from around 2 to 4 in trials published between 1982 and 1999 to much higher (less effective) values in studies published from 2010 onwards. Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses.</p

Chronic pain in Pachyonychia Congenita:evidence for neuropathic origin

Background: Pachyonychia congenita (PC) is a rare autosomal dominant skin disease with chronic pain being the most prominent complaint. Histological studies showing alterations in sensory innervation along with few reports on alterations in mechanical sensitivity suggest that PC may be a form of neuropathy.Objective: To systematically evaluate sensory function of PC patients vs. controls, here for the first time, in order to investigate PC pathophysiology.Methods: Patients (n=62) and controls (n=45) completed the McGill and Douleur Neuropathique-4 (DN4) questionnaires. Sensory testing included: detection and pain thresholds, pathological sensations, conditioned pain modulation (CPM) and temporal summation of pain (TSP).Results: A moderate-severe chronic pain in the feet, throbbing and stabbing in quality, was highly prevalent among PC patients (86%) and especially debilitating during weight bearing. In addition, the majority of patients had DN4 score ≥4 (62%), static allodynia (55%) and tingling (53%) in the feet. Compared to controls, PC patients exhibited thermal and mechanical hypoesthesia and mechanical hyperalgesia in the feet. CPM was reduced among the patients, and associated with more enhanced feet mechanical hyperalgesia. The specific gene and nature of the causative mutation did not affect any of these features.Conclusion: Although thermal and mechanical hypoesthesia may result from thicker skin, its presentation in painful regions along with mechanical hyperalgesia and allodynia point towards the possibility of neuropathic changes in PC. The clinical features and DN4 scores support this possibility and therefore neuropathic pain medications may be beneficial for PC patients. This article is protected by copyright. All rights reserved.</p

The effects of low doses of pregabalin on morphine analgesia in advanced cancer patients

Abstract OBJECTIVES: The aim of this study was to evaluate the opioid response in patients receiving morphine and pregabalin, independently from the presumed pain mechanisms, in comparison with patients receiving morphine treatment only. METHODS: A multicenter prospective randomized controlled study was carried out in a sample of 70 advanced cancer patients with pain requiring strong opioids. Thirty-five patients (group MO) were randomized to receive sustained-release morphine using initial doses of 60 mg/day. Thirty-five patients (group MO-PR) were randomized to start the same morphine doses and pregabalin in increasing doses, starting with 25 mg/day up to 150 mg/day in one week. The following data were also recorded before starting the treatments (T0) and then at week intervals for four weeks (W1-4): age, gender, primary cancer and known metastases, pain causes and mechanisms, symptoms associated with opioid therapy, pain intensity, Brief Pain Inventory (BPI), morphine doses and escalation indexes (OEIs), and quality of life. RESULTS: Forty-eight patients completed the study, twenty-eight and sixteen patients in group MO and MO-PR, respectively. Twenty patients were females, the mean age was 65.5 (± 10.3), and the mean Karnofsky status was 66.0 (± 18.9). No differences between groups were found in age (P = 0.839), Karnofsky status (P = 0.741), opioid doses as well as escalation indexes (OEI mg, P = 0.260, and OEI%, P = 0.270). No differences between the two groups were found in quality of life and all BPI items. CONCLUSION: The use of low doses of pregabalin added to morphine therapy in advanced cancer patients does not seem to provide advantageous analgesic effects, despite limitations of the present study due to the number of drop-outs

Topical gabapentin gel alleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury neuropathic pain model

Background: Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side effects. Localized therapy may curtail such side effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. Methods: Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three-times daily on the ipsilateral or contralateral plantar surface of the hind-paw while in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic- mechano-allodynia (paw withdrawal threshold [PWT] to von-Frey filament application and latency [PWL] to light brushing), coldallodynia (paw withdrawal duration [PWD] to acetone), heat- (PWL and PWD) and mechanohyperalgesia (PWD to pin-prick) were utilized to assess pain while effects on locomotion (open field) and motor balance (rotarod and footprint-analysis) were measured on days 5-30 postsurgery. Results: Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. Conclusions: These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes

Postsynthesis modification of a cellulose acetate ultrafiltration membrane for applications in water and wastewater treatment

A technique for postsynthesis modification of a cellulose acetate ultrafiltration membrane with possible application in water and wastewater treatment is studied. The technique used an oxidizing agent (persulfate) to develop free radicals on the membrane surface, and that was expected to promote grafting of hydrophilic macromolecules (polyethylene glycol). A chain-transfer agent (2-mercaptoethanol) was tested to control the grafting process, avoiding the formation of long chains that usually lead to high permeability losses in other graft techniques. The modifications aimed at the decrease of the fouling susceptibility of the membrane studied. The possibility of an increase in rejection was also investigated. The membrane was characterized before and after modification, by attenuated total reflectance-Fourier transform-infrared spectroscopy, scanning electron microscopy, atomic force microscopy, and in terms of the rejection of neutral reference solutes. The information given by the different techniques of characterization provided strong evidences of the occurrence of modification, although permeation of (real) foulants was the decisive test. To obtain information about the fouling tendency of the nonmodified and modified membranes, two different kinds of foulants were used: a humic acid (usually found in surface waters) and textile auxiliaries (representing one of the most important industries in Portugal). The results showed an increase in the rejections of the humic acid, and significant improvements in the performance of the membrane with respect to fouling tendency in the case of the textile auxiliarie

Current Status and Future Directions of Pain-Related Outcome Measures for Post-Surgical Pain Trials

Background: Clinical trials remain vital in order to: A) develop new treatment interventions, and also, B) to guide optimal use of current interventions for the treatment and prevention of acute and chronic postsurgical pain. Measures of pain (e.g. intensity and relief) and opioid use have been validated for the settings of postsurgical pain and continue to effectively guide research in this field.. Methods: This narrative review considers needs for innovation in postsurgical pain trial outcomes assessment. Results: Future improvements are needed and include: A) more widespread measurement of movement-evoked pain with validation of various procedure-relevant movemen-tevoked pain maneuvers; B) new validated analytical approaches to integrate early postoperative pain scores with opioid use; and, C) closer attention to the measurement of postoperative opioid use after hospital discharge. In addition to these traditional measures, consideration is being given to the use of new pain-relevant outcome domains that include: 1) other symptoms (e.g. nausea and vomiting), 2) recovery of physiological function (e.g. respiratory, gastrointestinal, genitourinary and musculoskeletal), 3) emotional function (e.g. depression, anxiety) and, 4) development of chronic postsurgical pain. Also, there is a need to develop pain-related domains and measures for evaluating both acute and chronic post-operative pain. Finally, evidence suggests that further needs for improvements in safety assessment and reporting in postsurgical pain trials is needed, e.g. by using an agreed upon, standardized collection of outcomes that will be reported as a minimum in all postsurgical pain trials. Conclusions: These proposed advances in outcome measurement methodology are expected to improve the success by which postsurgical pain trials guide improvements in clinical care and patient outcomes