Summary Background Neuropathic pain is difficult to treat. New treatments, clinical trials and standards of quality for assessing evidence justify an update of evidence-based recommendations for its pharmacological treatment. Methods The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain conducted a systematic review of randomised double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including unpublished trials (retrieved from clinicaltrials.gov and pharmaceutical websites). Meta-analysis used Numbers Needed to Treat (NNT) for 50 % pain relief as primary measure and assessed publication bias. Recommendations used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Findings In total 229 studies were included. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-review journals reported greater effects than online studies (R2=9·3%, p<0·01). Trial outcomes were generally modest even for effective drugs : in particular NNTs were 3·6 (95 % CI 3·0–4·4) for tricyclic antidepressants (TCAs), 6·4 (95 % CI 5·2–8·4) for serotonin- noradrenaline reuptake inbibitor (SNRI) antidepressants duloxetine and venlafaxine, 7·7 (95 % CI 6·5–9·4) for pregabalin and 6·3 (95 % CI 5·0–8·3) for gabapentin. NNTs were higher for gabapentin ER/enacarbil and capsaicin high concentration patches, lower for opioids and botulinum toxin A (BTX-A) and undetermined for lidocaine patches. Final quality of evidence was lower for lidocaine patches and BTX-A. Tolerability/safety and values/preferences were high for lidocaine patches and lower for opioids and TCAs. This permitted a strong GRADE recommendation for use and proposal as first line for TCAs, SNRIs, pregabalin, gabapentin and gabapentin ER/enacarbil in neuropathic pain, a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin patches and tramadol, and a weak recommendations for use and proposal as third line for strong opioids (particularly oxycodone and morphine) and BTX-A. Data for cannabinoids, tapentadol, drug combinations, and several other antiepileptics, antidepressants and topical drugs were inconclusive. Interpretation Limited efficacy, large placebo responses, inadequate diagnostic criteria and poor phenotypic profiling probably account for modest trial outcomes and should be taken into account in future studies. Funding This study was funded by NeuPSIG.

et al. JAMA 2015;313:1133-42.Conclusions: Regular aspirin and/or NSAID use is associated with a lower risk of colorectal cancer and is tied to specific genetic variants.Summary: There is data that suggests that the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a lower risk of colorectal neoplasms. (Chan AT, JAMA 2005; 294:914-923 and Friis S et al, Cancer Causes Control 2009; 20:731-740 and Rothwell PM et al, Lancet 2010; 376:1741-1750 Since virtually all vascular surgical patients are treated with aspirin or other antiplatelet agents with potential anti-inflammatory actions, the association of decreased colorectal cancer risks in such patients is of potential interest to those treating vascular surgical patients. The mechanisms, however, behind the association are not well understood. Chemo prevention of cancer is not currently recommended because of the uncertainty of risk benefit profile. The authors sought to identify genetic markers that characterize individuals who may obtain differential benefit from aspirin and NSAIDs. They conducted a discover-based, genome-wide analysis of gene X environment interactions between use of aspirin, NSAIDs or both and single nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. This was a case controlled study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia and Germany including colorectal cancer cases (N ¼ 8634) and matched controls (N ¼ 8553), ascertained between 1976 and 2011. All participants were of European descent. Overall regular use of aspirin and/or NSAIDs was associated with a lower risk of colorectal cancer (prevalence, 28% vs 38%; odd ratio [OR], 0.69 [95% CI, 0.64-0.74]; P ¼ 6.2 x 10 À28 ) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P ¼ 4.6 x 10 À9 for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with re2965667-TT genotype (prevalence, 28% vs 38% OR, 0.66 [95% CI, 0.61-0.70]; P ¼ 7.7 x 10 À33 ) but with a higher rate risk among those with rare TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P ¼ .002). In case-only interaction analysis, the SNP re 16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P ¼ 8.2 x 10 À9 for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P¼1.9 x 10 À30 ) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P ¼ .76).

The redefinition of neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system,” which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the “definite” level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.

There is tremendous inter-patient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for “precision medicine”, or personalized pain therapeutics (i.e., empirically-based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain, and the success rates for putative analgesic drugs in Phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.

The treatment of chronic pain with medicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and a significant reduction in opioid use. Results suggest long-term benefit of cannabis treatment in this group of patients, but the study's noncontrolled nature should be considered when extrapolating the results.