Efficacy and safety of botulinum A toxin for the treatment of chronic peripheral neuropathic pain: A systematic review of randomized controlled trials and meta-analysis

Background and objective: Botulinum toxin type A (BTX-A) is a recently developed treatment for the management of peripheral neuropathic pain. The objective of this study was to provide a synthesis of the evidence concerning the efficacy and safety of subcutaneous botulinum toxin type A injections.

Databases and data treatment: We searched the MEDLINE, EMBASE, LILACS, Cochrane, and Clinical Trial Register databases for randomized controlled trials comparing subcutaneous BTX-A to placebo injections for treating chronic peripheral neuropathic pain. The primary endpoint was the assessment of pain 1 month after the injection. The secondary outcomes were the assessment of pain at 3 months, neuropathic pain intensity and quality of life at 1 and 3 months, and adverse effects. A random-effect meta-analysis was performed on the combined data. Evidence quality was rated by the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method.

Results: Ten randomized controlled trials including 505 patients were included in this review (registration number CRD42021239108). At 1 and 3 months after injection, the BTX-A groups had a lower mean difference (MD) in pain score (MD -1.87 (confidence intervals [CIs] -2.91; -0.83) and -1.38 (CI -1.95; -0.81), respectively). Subgroup analysis showed greater efficacy for diabetic polyneuropathy (MD -2.48, [-3.22; -1.74]). We found no impact of BTX-A on quality of life and no difference in adverse effect between BTX-A and placebo. The evidence was considered of moderate quality.

Conclusion: The pooled data suggest that subcutaneous BTX-A injections have a clinically significant effect, decreasing pain for three months after the injection, but no benefit in terms of quality of life has yet been demonstrated.

Significance: We found that botulinum toxin is efficient and safe for the treatment of neuropathic pain, especially for diabetic polyneuropathy. Botulinum toxin type A, used for years in neurology, rehabilitation and physical medicine, has proved innocuous and effective, and should be considered as a serious alternative for pain treatment.