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Journal ArticleDOI

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

TL;DR: The results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain and allow a strong recommendation for use and proposal as first-line treatment in neuropathicPain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin.
Abstract: Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and E valuation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fi xed-eff ects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment eff ects. Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009). T rial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, fi nal quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These fi ndings permitted a strong recommendation for use and proposal as fi rst-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest effi cacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profi ling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.

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Citations
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TL;DR: In this paper, the authors provide an overview of wound healing pathophysiology with a focus on neural involvement in normal and diabetic wound healing, as well as future therapeutic perspectives to address the unmet needs of diabetic patients with chronic wounds.

24 citations

Journal ArticleDOI
TL;DR: Senicapoc, a stable and highly potent KCa3.1 inhibitor, is effective at reducing mechanical hypersensitivity in a rodent model of peripheral nerve injury and shows high CNS penetrance.

23 citations


Cites background from "Pharmacotherapy for neuropathic pai..."

  • ...Existing treatments for neuropathic pain provide effective relief to only 1 in 4 patients (Attal et al., 2010; Finnerup et al., 2015)....

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  • ...Expression of these targets in other areas of the CNS are believed to underlie their propensity to cause side effects such as sedation, euphoria and addiction (Finnerup et al., 2015)....

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Journal ArticleDOI
TL;DR: Clinical guidance is suggested for the positioning and daily use of opioids within cancer pain management and the efficacy and safety of a strong opioid treatment need to be re-evaluated and adapted to individuals constantly as it varies over time.
Abstract: Despite progress in treatments, cancer pain remains underestimated, poorly assessed and under-treated. Prescribing strong opioids, because of their specificities, requires precision in management considering their pharmacology but also a clear understanding of recommendations. Some clinicians highlight the risk of addiction, excessive sedation and respiratory depression and their need for information. Our objective in this review is to suggest some clinical guidance for the positioning and daily use of opioids within cancer pain management. Critical reflection based on literature analysis and clinical practice. Strong opioids may be initiated as soon as pain diagnosis is defined. Factors to consider are pain aetiology, opioid pharmacokinetics and pharmacodynamics, genetic polymorphism, physiology (age, gender, weight and pregnancy), comorbidities (especially renal, hepatic, cardiovascular diseases), chronobiology, environmental factors, medication interference and treatment adherence. Achieving the best-balanced opioid treatment for background pain is complex, mainly due to the variable benefit/risk ratio between individuals and the experience of breakthrough cancer pain. Opioid initiation alongside a dynamic reassessment of pain should be fully integrated into the patient’s management to optimise analgesia. The efficacy and safety of a strong opioid treatment need to be re-evaluated and adapted to individuals constantly as it varies over time. Cancer pain is multimorphic and permanently changing due to disease evolution, curative treatments and disruptive events (concomitant treatments, pain from associated disease, comorbidities and complications, modifications of the environment). Well-managed opioids are the cornerstone of a complex environment requiring multidisciplinary dynamic assessments integrated into the patient’s care pathway.

23 citations

Journal ArticleDOI
TL;DR: In CCI rats, chronic ginsenoside Rf treatment partially reversed the upregulation of proinflammatory cytokines in the spinal cord and/or the DRG but elevated IL‐10, an anti‐inflammatory factor, in theDRG, and restored the balance between proinflammatory and anti‐ inflammatory cytokines.
Abstract: The aim of this study was to investigate whether ginsenoside Rf can effectively relieve pain hypersensitivity in a neuropathic pain rat model. Neuropathic pain was induced in rats by chronic constriction injury (CCI) to the right sciatic nerve. Ginsenoside Rf was administered intraperitoneally after CCI surgery. The von Frey filament test and forced swimming test were performed to examine pain hypersensitivity and depression-like behavior in rats. Western blot was used to measure the levels of inflammatory cytokines in the dorsal root ganglion (DRG) and the spinal cord. Pretreatment of ginsenoside Rf for 7 days did not affect the onset of mechanical allodynia in CCI rats; however, a single dose of ginsenoside Rf 1 day after surgery attenuated established mechanical allodynia in CCI rats. Additionally, chronic treatment of ginsenoside Rf 1 week before and 2 weeks after CCI surgery diminished mechanical allodynia and depression-like behavior without affecting spontaneous locomotor activity in CCI rats. Furthermore, in CCI rats, chronic ginsenoside Rf treatment partially reversed the upregulation of proinflammatory cytokines in the spinal cord and/or the DRG but elevated IL-10, an anti-inflammatory factor, in the DRG. Ginsenoside Rf alleviated neuropathic pain and its associated depression and restored the balance between proinflammatory and anti-inflammatory cytokines. Our results suggest that ginsenoside Rf may be a potential therapy for nerve injury-induced neuropathic pain.

23 citations


Cites background from "Pharmacotherapy for neuropathic pai..."

  • ...Neuropathic pain, one of the leading and disabling clinical problems, is commonly caused by peripheral nerve injuries and diseases, and its pain symptoms are not adequately controlled by currently available medical therapies (Finnerup et al., 2015)....

    [...]

Journal ArticleDOI
TL;DR: An update on the current knowledge of neuropathy chronicization processes with a focus on both neuronal and glial ion channels, as well as on channel-mediated intercellular communication in chronic neuropathies is provided.
Abstract: Neuropathic pain is caused by primary lesion or dysfunction of either peripheral or central nervous system. Due to its complex pathogenesis, often related to a number of comorbidities, such as cancer, neurodegenerative and neurovascular diseases, neuropathic pain still represents an unmet clinical need, lacking long-term effective treatment and complex case-by-case approach. We analyzed the recent literature on the role of selective voltage-sensitive sodium, calcium and potassium permeable channels and non-selective gap junctions (GJs) and hemichannels (HCs) in establishing and maintaining chronic neuropathic conditions. We finally focussed our review on the role of extracellular microenvironment modifications induced by resident glial cells and on the recent advances in cell-to-cell and cell-to-extracellular environment communication in chronic neuropathies. In this review, we provide an update on the current knowledge of neuropathy chronicization processes with a focus on both neuronal and glial ion channels, as well as on channel-mediated intercellular communication.

23 citations

References
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Journal ArticleDOI
TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

62,157 citations

Journal Article
TL;DR: The QUOROM Statement (QUality Of Reporting Of Meta-analyses) as mentioned in this paper was developed to address the suboptimal reporting of systematic reviews and meta-analysis of randomized controlled trials.
Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7 In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1 Conceptual issues in the evolution from QUOROM to PRISMA

46,935 citations

Journal ArticleDOI
13 Sep 1997-BMJ
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure

37,989 citations

Journal ArticleDOI
TL;DR: An instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research is described and its use to determine the effect of rater blinding on the assessments of quality is described.

15,740 citations

Journal ArticleDOI
24 Apr 2008-BMJ
TL;DR: The advantages of the GRADE system are explored, which is increasingly being adopted by organisations worldwide and which is often praised for its high level of consistency.
Abstract: Guidelines are inconsistent in how they rate the quality of evidence and the strength of recommendations. This article explores the advantages of the GRADE system, which is increasingly being adopted by organisations worldwide

13,324 citations

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