The efficacy of various interventions as good strategies to reduce pain in botulinum neurotoxin A for wrinkles. A systematic review of the randomized controlled trials (RCTs).

Various topical interventions have been described to minimize botulinum neurotoxin-A (BoNT)-induced pain. The purpose of this study is to conduct a systematic review of relevant randomized controlled trials (RCTs) to compare the efficacy of pain relief methods during BoNT injection. PubMed, Scopus, and Web of Science were searched using "Botox," "Botulinum," or "BTX." We identified RCTs in which BoNT were injected to eliminate wrinkles. The pain score was the study outcome, and pain reduction method was compared with routine one. The meta-analysis was reported using the PRISMA checklist. The Higgins I(I²) statistical model assessed results heterogeneity. Two thousand one hundred and twenty-three articles were identified, thirteen articles eligible. Two hundred and sixty-two healthy volunteers were performed on these RCTs. Meta-analysis evaluated different methods to ease BoNT injection pain, and these methods significantly improved outcomes by 0.23% (95%CI, 0.11-0.46, p = .000). Subgroup analysis based on injection area showed no significant heterogeneity, but heterogeneity decreased when subgroup analysis based on other methods was done (Cochran's Q test = 115.52, p = .0001, I² = 87.9%). This meta-analysis confirms the effectiveness of pain relief methods during BoNT injection. Evaluation of different methods showed their effectiveness, but finding the best method requires comparative studies, although the role of pH and EMLA has been proven.