Suzetrigine, a selective NaV1.8 inhibitor in acute and chronic pain: mechanistic insights, clinical outcomes, and future perspectives.

PURPOSE OF REVIEW: The opioid epidemic and limitations of current nonopioid analgesics have created a need for safer, effective pain therapies. Suzetrigine, a first-in-class selective NaV1.8 inhibitor, was approved by the Food and Drug Administration in 2025 for the treatment of moderate to severe acute pain. The purpose of this review is to discuss the mechanism and clinical efficacy of suzetrigine and its potential for addressing existing therapeutic gaps in pain management.

RECENT FINDINGS: Phase 3 trials have demonstrated that suzetrigine provides a statistically significant and clinically meaningful reduction in acute postoperative pain compared to placebo, with efficacy similar to hydrocodone/acetaminophen and a favorable safety profile. Mechanistic studies confirm selective peripheral NaV1.8 inhibition, minimizing central nervous system effects and abuse potential. Ongoing research is evaluating suzetrigine for chronic pain conditions including diabetic peripheral neuropathy and lumbosacral radiculopathy, though long-term efficacy and safety remain to be established.

SUMMARY: Suzetrigine represents a promising nonopioid alternative for acute pain and has the potential to fill a significant gap in pain management. While initial results are encouraging, future studies are needed to define its role in chronic pain and multimodal analgesia, and to establish long-term safety.