Muscimol as a treatment for nerve injury-related neuropathic pain: a systematic review and meta-analysis of preclinical studies

Background: Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical studies aimed at summarizing the evidence regarding the efficacy of muscimol administration in the amelioration of nerve injury-related neuropathic pain.Methods: Two independent researchers performed the screening process in Medline, Embase, Scopus and Web of Science extracting data were extracted into a checklist designed according to the PRISMA guideline. A standardized mean difference (SMD [95% confidence interval]) was calculated for each. To assess the heterogeneity between studies, I-2 and chi-square tests were utilized. In the case of heterogeneity, meta-regression and subgroup analyses were performed to identify the potential source.Results: Twenty-two articles met the inclusion criteria. Pooled data analysis showed that the administration of muscimol during the peak effect causes a significant reduction in mechanical allodynia (SMD = 1.78 [1.45-2.11]; P < 0.0001; I-2 = 72.70%), mechanical hyperalgesia (SMD = 1.62 [1.28-1.96]; P < 0.0001; I-2 = 40.66%), and thermal hyperalgesia (SMD = 2.59 [1.79-3.39]; P < 0.0001; I-2 = 80.33%). This significant amendment of pain was observed at a declining rate from 15 minutes to at least 180 minutes post-treatment in mechanical allodynia and mechanical hyperalgesia, and up to 30 minutes in thermal hyperalgesia (P < 0 .0001).Conclusions: Muscimol is effective in the amelioration of mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia, exerting its analgesic effects 15 minutes after administration for up to at least 3 hours.