SUZETRIGINE, A NEW SELECTIVE NaV1.8 INHIBITOR, AS A BREAKTHROUGH IN THE TREATMENT OF PAIN – A REVIEW ARTICLE
Abstract
Introduction and purpose: Pain, especially chronic, remains a major public health burden, often refractory to existing treatments and associated with significant individual and social costs. Recent advances in our understanding of voltage-gated sodium channels, particularly NaV1.8, have highlighted their pivotal role in nociceptive signal transmission in peripheral sensory neurons. Suzetrigine, a novel and highly selective NaV1.8 inhibitor, has emerged as a promising therapeutic candidate in this context.
Aim: This review aims to evaluate the efficacy, safety, and therapeutic potential of suzetrigine, a novel and selective NaV1.8 channel inhibitor, in pain management and to assess its role as a non-opioid alternative in modern pain treatment.
Materials and Methods: A comprehensive review of literature available in the PubMed database was performed. This process involved a thorough search of articles written in English containing the following key terms: “suzetrigine”, “selective voltage-gated sodium channels”, “pain”, “pain management”, “NaV1.8”. The gathered data was then scrupulously examined and analyzed.
Conclusion: Suzetrigine with its high NaV1.8 channel selectivity and robust acute pain efficacy may represent a breakthrough in analgesia and pain management strategies. By minimizing off-target effects commonly associated with non-selective sodium channel blockers, suzetrigine offers a compelling alternative to opioids in treatment of postoperative pain. Its role in chronic and neuropathic pain remains under active investigation, with promising but not yet definitive results.
References
Alorfi, N. M. (2023). Pharmacological Methods of Pain Management: Narrative Review of Medication Used. International Journal of General Medicine, 16, 3247–3256. https://doi.org/10.2147/IJGM.S419239
Bennett, D. L., Clark, A. J., Huang, J., Waxman, S. G., & Dib-Hajj, S. D. (2019). The Role of Voltage-Gated Sodium Channels in Pain Signaling. Physiological Reviews, 99(2), 1079–1151. https://doi.org/10.1152/physrev.00052.2017
Benzon, H. T., Elmofty, D., Shankar, H., Rana, M., Chadwick, A. L., Shah, S., Souza, D., Nagpal, A. S., Abdi, S., Rafla, C., Abd-Elsayed, A., Doshi, T. L., Eckmann, M. S., Hoang, T. D., Hunt, C., Pino, C. A., Rivera, J., Schneider, B. J., Stout, A., … Shanthanna, H. (2025). Use of corticosteroids for adult chronic pain interventions: Sympathetic and peripheral nerve blocks, trigger point injections - guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, and the International Pain and Spine Intervention Society. Regional Anesthesia and Pain Medicine, rapm-2024-105593. https://doi.org/10.1136/rapm-2024-105593
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
Breivik, H., Collett, B., Ventafridda, V., Cohen, R., & Gallacher, D. (2006). Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. European Journal of Pain (London, England), 10(4), 287–333. https://doi.org/10.1016/j.ejpain.2005.06.009
Catterall, W. A. (2023). Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology. Channels, 17(1), 2281714. https://doi.org/10.1080/19336950.2023.2281714
Gaskin, D. J., & Richard, P. (2012). The economic costs of pain in the United States. The Journal of Pain, 13(8), 715–724. https://doi.org/10.1016/j.jpain.2012.03.009
Ghlichloo, I., & Gerriets, V. (2025). Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK547742/
Hameed, S. (2019). Nav1.7 and Nav1.8: Role in the pathophysiology of pain. Molecular Pain, 15, 1744806919858801. https://doi.org/10.1177/1744806919858801
Harirforoosh, S., Asghar, W., & Jamali, F. (2013). Adverse effects of nonsteroidal antiinflammatory drugs: An update of gastrointestinal, cardiovascular and renal complications. Journal of Pharmacy & Pharmaceutical Sciences: A Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques, 16(5), 821–847. https://doi.org/10.18433/j3vw2f
Hijma, H. J., Siebenga, P. S., de Kam, M. L., & Groeneveld, G. J. (2021). A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults. Pain Medicine (Malden, Mass.), 22(8), 1814–1826. https://doi.org/10.1093/pm/pnab032
Hijma, H. J., van Brummelen, E. M. J., Siebenga, P. S., & Groeneveld, G. J. (2022). A phase I, randomized, double-blind, placebo-controlled, single- and multiple dose escalation study evaluating the safety, pharmacokinetics and pharmacodynamics of VX-128, a highly selective Nav 1.8 inhibitor, in healthy adults. Clinical and Translational Science, 15(4), 981–993. https://doi.org/10.1111/cts.13215
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
Kasimova, M. A., Granata, D., & Carnevale, V. (2016). Voltage-Gated Sodium Channels: Evolutionary History and Distinctive Sequence Features. Current Topics in Membranes, 78, 261–286. https://doi.org/10.1016/bs.ctm.2016.05.002
Keam, S. J. (2025). Suzetrigine: First Approval. Drugs, 85(6), 845–851. https://doi.org/10.1007/s40265-025-02178-w
Li, Z., Wu ,Qiurong, & and Yan, N. (2024). A structural atlas of druggable sites on Nav channels. Channels, 18(1), 2287832. https://doi.org/10.1080/19336950.2023.2287832
Maizels, M., & McCarberg, B. (2005a). Antidepressants and antiepileptic drugs for chronic non-cancer pain. American Family Physician, 71(3), 483–490.
Maizels, M., & McCarberg, B. (2005b). Antidepressants and antiepileptic drugs for chronic non-cancer pain. American Family Physician, 71(3), 483–490.
Mulcahy, J. V., Pajouhesh, H., Beckley, J. T., Delwig, A., Bois, J. D., & Hunter, J. C. (2019). Challenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform NaV1.7. Journal of Medicinal Chemistry, 62(19), 8695–8710. https://doi.org/10.1021/acs.jmedchem.8b01906
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
Raffaeli, W., Tenti, M., Corraro, A., Malafoglia, V., Ilari, S., Balzani, E., & Bonci, A. (2021). Chronic Pain: What Does It Mean? A Review on the Use of the Term Chronic Pain in Clinical Practice. Journal of Pain Research, 14, 827–835. https://doi.org/10.2147/JPR.S303186
Raja, S. N., Carr, D. B., Cohen, M., Finnerup, N. B., Flor, H., Gibson, S., Keefe, F. J., Mogil, J. S., Ringkamp, M., Sluka, K. A., Song, X.-J., Stevens, B., Sullivan, M. D., Tutelman, P. R., Ushida, T., & Vader, K. (2020). The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises. Pain, 161(9), 1976–1982. https://doi.org/10.1097/j.pain.0000000000001939
Rosenblum, A., Marsch, L. A., Joseph, H., & Portenoy, R. K. (2008). Opioids and the treatment of chronic pain: Controversies, current status, and future directions. Experimental and Clinical Psychopharmacology, 16(5), 405–416. https://doi.org/10.1037/a0013628
Sullivan, M. D., & Robinson, J. P. (2006). Antidepressant and anticonvulsant medication for chronic pain. Physical Medicine and Rehabilitation Clinics of North America, 17(2), 381–400, vi–vii. https://doi.org/10.1016/j.pmr.2005.12.006
Theile, J. W., & Cummins, T. R. (2011). Recent developments regarding voltage-gated sodium channel blockers for the treatment of inherited and acquired neuropathic pain syndromes. Frontiers in Pharmacology, 2, 54. https://doi.org/10.3389/fphar.2011.00054
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
Vertex Announces Positive Results From the VX-548 Phase 3 Program for the Treatment of Moderate-to-Severe Acute Pain | Vertex Pharmaceuticals Newsroom. (n.d.). Retrieved June 19, 2025, from https://news.vrtx.com/news-releases/news-release-details/vertex-announces-positive-results-vx-548-phase-3-program
Vertex Announces Results From Phase 2 Study of Suzetrigine for the Treatment of Painful Lumbosacral Radiculopathy | Vertex Pharmaceuticals Newsroom. (n.d.). Retrieved June 19, 2025, from https://news.vrtx.com/news-releases/news-release-details/vertex-announces-results-phase-2-study-suzetrigine-treatment
Vertex to Present Phase 3 Data Highlighting Suzetrigine’s Potential as a First-in-Class, Highly Selective Pain Signal Inhibitor at the American Society of Anesthesiologists Annual Meeting | Vertex Pharmaceuticals Newsroom. (n.d.). Retrieved June 19, 2025, from https://news.vrtx.com/news-releases/news-release-details/vertex-present-phase-3-data-highlighting-suzetrigines-potential
Wang, H., Huang, J., Zang, J., Jin, X., & Yan, N. (2024). Drug discovery targeting Nav1.8: Structural insights and therapeutic potential. Current Opinion in Chemical Biology, 83, 102538. https://doi.org/10.1016/j.cbpa.2024.102538
Wojtasik-Bakalarz, K., Woroń, J., & Siwek, M. (2021). Adverse effects of opioid analgesics from the central nervous system. Palliative Medicine in Practice, 15(3), Article 3. https://doi.org/10.5603/PMPI.2021.0013
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