Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.
Nanna B. Finnerup,Nadine Attal,Simon Haroutounian,Ewan D McNicol,Ralf Baron,Robert H. Dworkin,Ian Gilron,Maija Haanpää,Per Hansson,Per Hansson,Troels S. Jensen,Troels S. Jensen,Peter R. Kamerman,Karen Lund,Andrew Moore,Srinivasa N. Raja,Andrew S.C. Rice,Andrew S.C. Rice,Michael C. Rowbotham,Emily S. Sena,Emily S. Sena,Philip J. Siddall,Philip J. Siddall,Blair H. Smith,Mark S. Wallace +24 more
TLDR
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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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.read more
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Has Self-reported Marijuana Use Changed in Patients Undergoing Total Joint Arthroplasty After the Legalization of Marijuana?
Jason M Jennings,Michael A Williams,Daniel L. Levy,Roseann M. Johnson,Catherine L. Eschen,Douglas A. Dennis +5 more
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Peripheral administration of interleukin-13 reverses inflammatory macrophage and tactile allodynia in mice with partial sciatic nerve ligation
Norikazu Kiguchi,Haruka Sakaguchi,Yui Kadowaki,Fumihiro Saika,Yohji Fukazawa,Shinsuke Matsuzaki,Shiroh Kishioka +6 more
TL;DR: It is suggested that IL-13 reverses inflammatory macrophage-dependent neuropathic pain via a phenotype shift toward suppressive macrophages.
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Repeated Administration of Amitriptyline in Neuropathic Pain: Modulation of the Noradrenergic Descending Inhibitory System.
TL;DR: The results suggest that amitriptyline could still produce analgesia under pathological dysfunction of the descending noradrenergic system, and may enhance the analgesic effect of drugs for neuropathic pain that require normal descending nor adrenoceptor inhibition to production analgesia.
Journal ArticleDOI
NOX4 is an early initiator of neuropathic pain.
TL;DR: It is concluded that NOX4 is involved in the development of neuropathic pain states by producing oxidative stress and subsequent cytokine dysregulation at the lesion site explaining ineffectiveness of post‐acute pharmacological NOX inhibition.
Journal ArticleDOI
Antibodies binding the head domain of P2X4 inhibit channel function and reverse neuropathic pain.
Wendy A Williams,John E. Linley,Clare A. Jones,Yoko Shibata,Arjan Snijder,James Button,Jon P. Hatcher,Ling Huang,Bruck Taddese,Peter E. Thornton,Darren J. Schofield,George Thom,Bojana Popovic,Bhupinder Dosanjh,Trevor Wilkinson,Jane Hughes,Claire Dobson,Maria A T Groves,Carl I Webster,Andy Billinton,Tristan J Vaughan,Iain Chessell +21 more
TL;DR: The generation of a panel of diverse monoclonal antibodies to human and mouse P2X4, capable of both positive and negative modulation of channel function is described, and it is proposed that inhibitory mAbs binding the head domain of P2x4 have therapeutic potential for the treatment of neuropathic pain.
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