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

Anupam Datta Gupta, Suzanne Edwards, Jessica Smith, John Snow, Renuka Visvanathan, Graeme Tucker, David Wilson, Anupam Datta Gupta, Suzanne Edwards, Jessica Smith, John Snow, Renuka Visvanathan, Graeme Tucker, David Wilson

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.

Keywords: botulinum toxin; meta-analysis; neuropathic pain; systematic review.

Conflict of interest statement

Authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The mechanism and effect of botulinum toxin in neuropathic pain. Botulinum toxin reversibly inhibits the release of acetylcholine from the presynaptic vesicle and causes local chemodenervation resulting in reduced muscle contraction. The possible mechanisms of action on pain involves (i) retrograde axonal transport of toxin; (ii) inhibition of neuropeptides, such as substance P, calcitonin gene-related protein (CGRP), and glutamate; and (iii) deactivation of Na channel. All prevent peripheral and central sensitisation.
Figure 2
Figure 2
Final VAS.
Figure 3
Figure 3
Sleep.
Figure 4
Figure 4
Hospital anxiety and depression score.
Figure 5
Figure 5
Quality of life.
Figure 6
Figure 6
Funnel plot.
Figure 7
Figure 7
PRISMA diagram.

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