The Use of Botulinum Toxin Injections in Peripheral Neuropathic Pain: A Systematic Review of Efficacy and Safety...

Peripheral neuropathic pain (PNP), a chronic condition resulting from nerve damage and characterized by altered sensory signaling and central sensitization, poses significant therapeutic challenges. Botulinum toxin (BTX), known for neuromuscular blockades, also exhibits analgesic properties, prompting its investigation for PNP management. However, existing evidence regarding its efficacy and safety is fragmented. This systematic review aimed to synthesize current data on BTX injections for PNP. Guided by PRISMA and the neuromatrix theory, major databases (PubMed, Web of Science, Cochrane, Embase, Scopus, EBSCOhost) were searched up to March 2025. Included studies evaluated BTX (primarily type A) in adults with PNP using validated pain outcomes and reported safety, covering designs from randomized controlled trials (RCTs) to observational research. Independent reviewers performed data extraction and quality assessment using risk of bias tools. This review has been registered on Prospero with the following number: CRD420251022222. The patient groups studied (1343 participants: 547 males and 632 females) showed substantial variability in age, diagnosis, and treatment setting. Results indicated BTX use across diverse PNP etiologies (e.g., trigeminal neuralgia, painful diabetic neuropathy (DN), postherpetic neuralgia, and phantom limb pain) and across multiple countries. RCTs often reported statistically significant reductions in pain intensity and improvements in related outcomes compared with placebo, although effect sizes were heterogeneous and sample sizes were generally modest. Nonrandomized studies suggested similar trends but frequently presented moderate to serious risk of bias. Adverse events were usually mild and transient, most often localized injection-site reactions or temporary facial asymmetry in cranial applications, while serious complications were rare but could not be excluded with confidence because of incomplete safety reporting. Overall, BTX may offer clinically meaningful benefit for selected PNP subtypes, particularly trigeminal neuralgia and painful DN, yet the certainty of evidence remains low to moderate due to study limitations and methodological diversity. Routine use in PNP therefore requires cautious, individualized consideration rather than broad generalization.