• Alan D Kaye, Erin S Everett, Arianna M Lehuquet, Joseph W Mason, Rebecca Maitski, Michael J Plessala, Sonnah Barrie, Carlo Jean Baptiste, George Mychaskiw, Shahab Ahmadzadeh, Sahar Shekoohi, and Giustino Varrassi.
• Departments of Anesthesiology and Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA.
• Curr Pain Headache Rep. 2024 Nov 1; 28 (11): 113511431135-1143.

Purpose Of ReviewDespite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens.Recent FindingsHowever, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse. Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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