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
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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pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies.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 Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009).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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Thiourea Modified Doxorubicin: A Perspective pH-Sensitive Prodrug.
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Prophylactic treatment with the tricyclic antidepressant desipramine prevents development of paclitaxel-induced neuropathic pain through activation of endogenous analgesic systems.
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The time course of brief and prolonged topical 8% capsaicin-induced desensitization in healthy volunteers evaluated by quantitative sensory testing and vasomotor imaging
TL;DR: Time-dependent functional recovery was almost complete 21 days after the 24 h capsaicin exposure, while recovery of neurogenic inflammatory responsiveness remained partial, and psychophysically assessed sensory deficiencies induced by the used 8% Capsaicin–ablation correspond well with a predominant effect on TRPV1+–cutaneous fibers.
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Effectiveness and safety of 5% lidocaine-medicated plaster on localized neuropathic pain after knee surgery: a randomized, double-blind controlled trial.
TL;DR: Beyond the inhibition of sodium channels by LP5, these findings suggest the involvement of cold and mechanical receptors that participate to pain chronicisation and also of the non-negligible placebo effect of the patch, items that need to be explored further and challenged in other etiologies of localized neuropathic pain.
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