Korean J Pain.  2023 Oct;36(4):425-440. 10.3344/kjp.23161.

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

• Ramawad HA
• Paridari P
• Jabermoradi S
• Gharin P
• Toloui A
• Safari S
• Yousefifard M

• KMID: 2546705
• DOI: http://doi.org/10.3344/kjp.23161

Abstract

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, I² 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; I² = 72.70%), mechanical hyperalgesia (SMD = 1.62 [1.28–1.96]; P < 0.0001; I² = 40.66%), and thermal hyperalgesia (SMD = 2.59 [1.79–3.39]; P < 0.0001; I² = 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.

Keyword

Analgesia; Gamma-Aminobutyric Acid; Hyperalgesia; Meta-Analysis; Muscimol; Neuralgia; Pain; Peripheral Nerve Injuries; Spinal Cord Injuries

Figure

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  Fig. 1 PRISMA flow diagram of the article selection process.

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  Fig. 2 The effect of muscimol administration on nerve injury-related mechanical allodynia in observed peak effect time. SD: standard deviation, 95% CI: 95% confidence interval.

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  Fig. 3 Meta-regression for the assessment of dose-effect and follow-up duration on muscimol efficacy in nerve injury-related mechanical allodynia (A, B), mechanical hyperalgesia (C, D), and thermal hyperalgesia (E, F). 95% CI: 95% confidence interval.

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  Fig. 4 The effect of muscimol on nerve injury-related mechanical hyperalgesia (A) and thermal hyperalgesia (B) in the observed peak effect time. SD: standard deviation, 95% CI: 95% confidence interval.

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  Fig. 5 Publication bias for assessment of muscimol on nerve injury-related neuropathic pain.

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