Beyond Conventional Analgesics

Background: Neuralgia is a chronic neuropathic pain condition characterized by recurrent paroxysms of severe pain that are often refractory to conventional pharmacological therapies. Botulinum toxin type A (BTX-A) has emerged as a promising adjunctive treatment due to its analgesic and neuromodulatory properties. Objective: Evidence from randomized controlled trials (RCTs) remains heterogeneous, with variability in dosage, injection protocols, and follow-up duration. In addition, prior meta-analyses lacked detailed subgroup analyses, and several RCTs combined BTX-A with concomitant long-term analgesics, obscuring its independent therapeutic effect. This study aimed to provide a comprehensive synthesis of the efficacy and safety of BTX-A monotherapy for neuralgia, while permitting the use of acute analgesics (PROSPERO registration: CRD420251042926). Methods: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science for RCTs published up to September 2025 that evaluated BTX-A monotherapy in adults with neuralgia. Study selection and data extraction adhered to PRISMA 2020 guidelines. Pooled effect sizes were calculated using random-effects models, and heterogeneity was quantified with the I² statistic. Prespecified subgroup analyses were conducted based on dosage and follow-up duration. Results: Seven RCTs encompassing 368 participants were included. Compared with placebo or standard therapy, BTX-A significantly reduced pain intensity (VAS), attack frequency, and rescue analgesic use, while improving sleep quality, quality of life (QoL), and patient global impression of change (PGIC). Subgroup analysis revealed that low-dose regimens (<50 U) achieved comparable analgesic efficacy and durability to higher doses, with effects sustained for approximately three months. No serious adverse events were reported. Conclusions: BTX-A monotherapy provides clinically meaningful pain relief and functional improvement in patients with neuralgia, including trigeminal and postherpetic neuralgia. Its favorable safety profile and sustained efficacy support its role as an effective adjunct or alternative for refractory neuropathic pain. Future large-scale RCTs with standardized dosing and extended follow-up are warranted to optimize treatment protocols.