• Marc Russo, Brett Graham, and Danielle M Santarelli.
• Hunter Pain Specialists, Broadmeadow, New South Wales, Australia.
• Pain Pract. 2023 Jan 1; 23 (1): 636963-69.

BackgroundGabapentin is a recommended first-line agent for treating neuropathic pain; however, its efficacy rate is reportedly low, and the risk of adverse events is high. A plausible explanation for this lies with its wide range of actions, the entirety of which have yet to be fully elucidated.MethodsA review of the literature was conducted on gabapentin's known and proposed analgesic mechanisms of action, as well as potentially opposing or detrimental actions.ResultsGabapentin's classical analgesic mechanisms involve direct attenuation of excitatory neurotransmission in the spinal cord via inhibition of neuronal ion channels, while indirect mechanisms include descending inhibition and block of injury-evoked synaptogenesis. Glial effects have also been reported; however, whether they are neuroprotective or detrimental is unknown. Furthermore, data from animal models do not reflect clinical outcomes.ConclusionsGabapentin's clinical use should be reconsidered according to the net effects of its numerous assumed actions, including the tripartite synapse and oligodendrocyte effects. Whether it is doing more harm than good, especially in the scenarios of incomplete or loss of response, warrants consideration when prescribing gabapentin.© 2022 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.

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