SUZETRIGINE AND THE FUTURE OF ANALGESIA: A NEW NON-OPIOID APPROACH TO PAIN MANAGEMENT

Authors

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6079

Keywords:

Suzetrigine, VX-548, NaV1.8, Pain Management, Non-Opioid Analgesics, Acute Pain, Analgesia, Opioid Alternatives

Abstract

Introduction: Pain remains one of the most prevalent health problems worldwide and a major cause of disability, reduced quality of life and healthcare utilization. Although opioid analgesics have long been considered the cornerstone of treatment for moderate-to-severe pain, their use is associated with substantial risks, including tolerance, dependence, addiction and overdose. Consequently, the development of effective non-opioid analgesics has become a priority in pain medicine. Suzetrigine (VX-548), a selective voltage-gated sodium channel NaV1.8 inhibitor, has recently emerged as a promising therapeutic option for acute pain management.

Purpose: The aim of this review is to evaluate the current evidence regarding suzetrigine as a novel non-opioid analgesic and to discuss its potential role in the future of pain management. Particular attention is given to the clinical burden of pain, the limitations of existing analgesic therapies, the biological rationale for targeting NaV1.8 channels, and the efficacy and safety of suzetrigine.

Methodology: A narrative review of literature was conducted using published preclinical studies, clinical trials, review articles, systematic reviews and meta-analyses concerning suzetrigine and NaV1.8 inhibition using PubMed and Clinicaltrials.gov. The reviewed literature included studies evaluating pharmacological properties, mechanism of action, clinical efficacy, safety profile and potential therapeutic applications of suzetrigine in acute and chronic pain conditions.

Conclusion: Current evidence indicates that suzetrigine represents a significant advancement in analgesic drug development. By selectively inhibiting NaV1.8 channels involved in peripheral nociceptive signaling, it provides effective pain relief without engaging opioid pathways. Clinical studies have demonstrated favorable efficacy and tolerability in patients, with moderate-to-severe acute pain, while ongoing research continues to explore its potential applications in chronic and disease-specific pain conditions. Suzetrigine may therefore contribute to reducing reliance on opioid analgesics and represents a promising step toward safer pain management strategies.

References

Ali, M. Y., Antunes, F. T. T., Huang, S., Chen, L., & Zamponi, G. W. (2025). Pharmacological inhibition of NaV1.8 by suzetrigine reveals potent analgesic potential without tolerance development in mice. Molecular Brain, 18(1), 86. https://doi.org/10.1186/s13041-025-01253-3

Alvarez-Aguilar, P., & Picado-Loaiza, S. (2026). Suzetrigine (a NaV1.8 inhibitor) versus placebo for acute postoperative pain: A systematic review and meta-analysis of randomized controlled trials. Medicine, 105(10), e47877. https://doi.org/10.1097/MD.0000000000047877

Attal, N., & Barrot, M. (2025). Targeting Nav1.8 with the nonopioid antagonist suzetrigine for analgesia: Cause for optimism? British Journal of Anaesthesia, 135(4), 829–832. https://doi.org/10.1016/j.bja.2025.07.043

Bansal, S., Gupta, S. K., Dutta, S., Shah, R. B., & Singhal, S. (2026). Selective Nav1.8 inhibition by suzetrigine, a novel nonopioid analgesic for acute pain management: A systematic review and metanalysis. Saudi Journal of Anaesthesia, 20(1), 82–91. https://doi.org/10.4103/sja.sja_602_25

Bertoch, T., D’Aunno, D., McCoun, J., Solanki, D., Taber, L., Urban, J., Oswald, J., Swisher, M. W., Tian, S., Miao, X., Correll, D. J., Negulescu, P., Bozic, C., & Weiner, S. G. (2025). Suzetrigine, a nonopioid Na V 1.8 inhibitor for treatment of moderate-to-severe acute pain: Two phase 3 randomized clinical trials. Anesthesiology, 142(6), 1085–1099. https://doi.org/10.1097/ALN.0000000000005460

Bradshaw, J. C., Lester, L., & Leon, D. A. (2026). Suzetrigine for acute pain in the emergency department: A first-in-class NaV1.8 blocker. Journal of the American College of Emergency Physicians Open, 7(2), 100337. https://doi.org/10.1016/j.acepjo.2026.100337

Chen, S. L., Liu, M. A., & Swisher, M. W. (2026). Suzetrigine, a selective NaV1.8 inhibitor in acute and chronic pain: Mechanistic insights, clinical outcomes, and future perspectives. Current Opinion in Anaesthesiology, 39(2), 183–187. https://doi.org/10.1097/ACO.0000000000001599

Hang Kong, A. Y., Tan, H. S., & Habib, A. S. (2024). VX-548 in the treatment of acute pain. Pain Management, 14(9), 477–486. https://doi.org/10.1080/17581869.2024.2421749

Hasoon, J., Nguyen, A., Govindaraj, R., & Robinson, C. L. (2026). Suzetrigine for cancer-related bone pain: A three-patient case series. Orthopedic Reviews, 18, 162158. https://doi.org/10.52965/001c.162158

Hu, S., Lyu, D., & Gao, J. (2025). Suzetrigine: The first Nav1.8 inhibitor approved for the treatment of moderate to severe acute pain. Drug Discoveries & Therapeutics, 19(1), 80–82. https://doi.org/10.5582/ddt.2025.01010

Jo, S., Fujita, A., Osorno, T., Stewart, R. G., Vaelli, P. M., & Bean, B. P. (2025). Differential state-dependent Nav1.8 inhibition by suzetrigine, LTGO-33, and A-887826. The Journal of General Physiology, 157(4), e202413719. https://doi.org/10.1085/jgp.202413719

Jones, J., Correll, D. J., Lechner, S. M., Jazic, I., Miao, X., Shaw, D., Simard, C., Osteen, J. D., Hare, B., Beaton, A., Bertoch, T., Buvanendran, A., Habib, A. S., Pizzi, L. J., Pollak, R. A., Weiner, S. G., Bozic, C., Negulescu, P., White, P. F., & VX21-548-101 and VX21-548-102 Trial Groups. (2023). Selective inhibition of NaV1.8 with VX-548 for acute pain. The New England Journal of Medicine, 389(5), 393–405. https://doi.org/10.1056/NEJMoa2209870

Joudeh, S., Moore, D., Hasoon, J., Robinson, C. L., Idowu, M., & Oso, T. (2026). Suzetrigine for vaso-occlusive pain in sickle cell disease: A three-patient case series. Orthopedic Reviews, 18, 162149. https://doi.org/10.52965/001c.162149

Koivisto, A.-P. (2026). Mapping the extended pain pathway: Human genetic and multi-omic strategies for next-generation analgesics. International Journal of Molecular Sciences, 27(7), 3035. https://doi.org/10.3390/ijms27073035

Mach, M., Giba, A., Miedziaszczyk, M., Bryla, A., & Szkutnik-Fiedler, D. (2025). Suzetrigine as a novel non-opioid analgesic drug in pain management: A review of clinical evidence and therapeutic perspectives. Cureus, 17(8), e90755. https://doi.org/10.7759/cureus.90755

McCoun, J., Winkle, P., Solanki, D., Urban, J., Bertoch, T., Oswald, J., Swisher, M. W., Taber, L. A., Healey, T., Jazic, I., Correll, D. J., Negulescu, P. A., Bozic, C., Weiner, S. G., & VX-548-107 Study Team. (2025). Suzetrigine, a non-opioid NaV1.8 inhibitor with broad applicability for moderate-to-severe acute pain: A phase 3 single-arm study for surgical or non-surgical acute pain. Journal of Pain Research, 18, 1569–1576. https://doi.org/10.2147/JPR.S509144

Mohiuddin, A. L., & Ahmed, Z. (2025). Suzetrigine - a novel FDA-approved analgesic - opportunities, challenges and future perspectives: A perspective review. Health Science Reports, 8(11), e71545. https://doi.org/10.1002/hsr2.71545

Osteen, J. D., Immani, S., Tapley, T. L., Indersmitten, T., Hurst, N. W., Healey, T., Aertgeerts, K., Negulescu, P. A., & Lechner, S. M. (2025). Pharmacology and mechanism of action of suzetrigine, a potent and selective NaV1.8 pain signal inhibitor for the treatment of moderate to severe pain. Pain and Therapy, 14(2), 655–674. https://doi.org/10.1007/s40122-024-00697-0

Peshin, S., Villa Celi, C., Rashid, S., Rego, A., & Baumrucker, S. J. (2025). Pharmacology update: Suzetrigine: A novel NaV1.8 sodium channel inhibitor for acute pain management. The American Journal of Hospice & Palliative Care, 10499091251353455. https://doi.org/10.1177/10499091251353455

Pham, A., Yep, H., Wozniak, S., Javvaji, A., Nada, E., & Bergese, S. (2025). Beyond opioids: A review of suzetrigine for acute pain management. International Journal of Molecular Sciences, 26(20), 9865. https://doi.org/10.3390/ijms26209865

Rajasingham, R., & Qi, Y. (2025). Suzetrigine, a non-opioid small-molecule analgesic: Mechanism of action, clinical, and translational science. Clinical and Translational Science, 18(11), e70414. https://doi.org/10.1111/cts.70414

Rejeev, M. M., Pavithran, K., & Palatty, P. (2025). Clinical efficacy and safety profile of suzetrigine: A novel non-opioid analgesic targeting NaV1.8 sodium channel. Cureus, 17(11), e96054. https://doi.org/10.7759/cureus.96054

Sibomana, O., Okereke, M., & Hakayuwa, C. M. (2025). Suzetrigine approval breaks a 25-year silence: A new era in non-opioid acute pain management. Journal of Pain Research, 18, 2805–2808. https://doi.org/10.2147/JPR.S526851

Stewart, R. G., Osorno, T., Fujita, A., Jo, S., Ferraiuolo, A., Carlin, K., & Bean, B. P. (2025). Modulation of human dorsal root ganglion neuron firing by the Nav1.8 inhibitor suzetrigine. Proceedings of the National Academy of Sciences of the United States of America, 122(22), e2503570122. https://doi.org/10.1073/pnas.2503570122

Vaelli, P., Fujita, A., Jo, S., Zhang, H.-X. B., Osorno, T., Ma, X., & Bean, B. P. (2024). State-dependent inhibition of Nav1.8 sodium channels by VX-150 and VX-548. Molecular Pharmacology, 106(6), 298–308. https://doi.org/10.1124/molpharm.124.000944

Wood, J. N., Yan, N., Huang, J., Zhao, J., Akopian, A., Cox, J. J., Woods, C. G., & Nassar, M. A. (2025). Sensory neuron sodium channels as pain targets; from cocaine to Journavx (VX-548, suzetrigine). The Journal of General Physiology, 157(4), e202513778. https://doi.org/10.1085/jgp.202513778

Wu, Z., & Lu, D. (2026). Advances in the discovery of selective NaV1.8 inhibitors for pain management. European Journal of Medicinal Chemistry, 302(Pt 2), 118326. https://doi.org/10.1016/j.ejmech.2025.118326

Yuan, S., Ji, H., Lu, Y., Zhang, Z., & Tang, H. (2026). The clinical application of suzetrigine. Journal of Pain & Palliative Care Pharmacotherapy, 40(2), 311–320. https://doi.org/10.1080/15360288.2026.2624502

Downloads

Published

2026-09-21

How to Cite

Witkowska, Z., Ostrowska, Z., Paprocki, O., Rutka, B., Jastrzębska, B., Danieluk, A., Kulińska, A., Kądziela, J., Soćko, G., Tańska, J., & Komorowska, A. (2026). SUZETRIGINE AND THE FUTURE OF ANALGESIA: A NEW NON-OPIOID APPROACH TO PAIN MANAGEMENT. International Journal of Innovative Technologies in Social Science, 4(3(51). https://doi.org/10.31435/ijitss.3(51).2026.6079

Most read articles by the same author(s)