A Systematic Review and Meta-Analysis of Efficacy of Botulinum Toxin A for Neuropathic Pain

Abstract

We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep outcomes. We conducted a Cochrane Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria analysis of RCTs from the following data sources: EMBASE, CINAHL, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane database, Cochrane Clinical Trial Register, Australia New Zealand Clinical Trials Registry, and EU Clinical Trials Register. Meta-analysis of 17 studies showed a mean final VAS reduction in pain in the intervention group of 2.59 units (95% confidence interval: 1.79, 3.38) greater than the mean for the placebo group. The overall mean difference for sleep, Hospital Anxiety and Depression Scale (HADS) anxiety, HADS depression, and QOL mental and physical sub-scales were, respectively, 1.10 (95% CI: −1.71, 3.90), 1.41 (95% CI: −0.61, 3.43), −0.16 (95% CI: −1.95, 1.63), 0.85 (95% CI: −1.85, 3.56), and −0.71 (95% CI: −3.39, 1.97), indicating no significance. BoNT-A is effective for NP; however, small-scale RCTs to date have been limited in evidence. The reasons for this are discussed, and methods for future RCTs are developed to establish BoNT-A as the first-line agent.

Effects of Intradermal Botulinum Toxin Injections on Herpes Zoster Related Neuralgia

“…Botulinum toxin type A has been used for years in the fields of neurology, rehabilitation and physical medicine and has proven to be an innocuous and effective therapy. 13 , 22 It seems that BoNT-A might also be effective for the comprehensive management of neuropathic pain, especially for diabetic polyneuropathy. 23 BoNT-A can accelerate nerve regeneration and improve functional recovery after injury to peripheral nerves.…”

“… 12 With regard to its effects on pain, some possible mechanisms of BoNT-A include retrograde axonal transport of toxins, inhibition of neuropeptides, such as substance P and calcitonin gene-related protein (CGRP), glutamate and deactivation of Na channels. 13 …”

Subcutaneous BoNT/A Injection for Intractable Pain and Disability in Complex Regional Pain Syndrome: A Case Report

“…In the first round of injections, we treated only the ulnar territory, while in the following rounds, we decided to apply a more widespread approach with an improvement of the efficacy on the pain and disability as well as a longer duration of the benefit; in fact, low doses of BoNT/A are insufficient for the spreading into the central nervous system [36,38]. Regarding the efficacy of BoNT/A in neuropathic pain, a recent meta-analysis of randomized controlled studies reported greater efficacy of BoNT/A in reducing pain than placebo [39]. In the context of CRPS, a meta-analysis of placebo responses in long-standing CRPS patients reported no evidence of placebo response [40], but there were no studies regarding therapy with BoNT/A.…”

Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update

“…Adjunctive local BoNT/A1 injection seems to be a safe and effective therapy in long-term management for chronic neuropathic pain (Ri et al 2021 ). The most recent systematic review and meta-analysis of randomized controlled studies added evidence that BoNT-A1 is safe for treating neuropathic pain, without notable side effects, and it is durable over an extended period (Datta Gupta et al 2022 ).…”