{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:34:28Z","timestamp":1790091268848,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The ongoing opioid epidemic in the United States highlights the need for novel analgesics with reduced risk of misuse, dependence, and adverse central nervous system effects. Suzetrigine (trade name Journavx), a first-in-class selective Nav1.8 (a sodium channel expressed in peripheral nociceptors) inhibitor, was approved by the FDA in early 2025 and marketed as the first non-opioid analgesic in over two decades. Current studies have shown that suzetrigine has potential in treating acute pain perioperatively for minimally to moderately painful ambulatory procedures. However, suzetrigine appears less potent than hydrocodone-acetaminophen in this context, and it remains unclear how effective suzetrigine is in treating more severe postoperative pain. Notably, all current studies are limited to short durations of treatment; further studies will be required to delineate suzetrigine\u2019s long-term efficacy, safety, and addiction potential to be utilized in the management of chronic pain patients. This article provides a review of the current literature available on the use of suzetrigine in treating acute pain.<\/jats:p>","DOI":"10.3390\/ijms26209865","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:16Z","timestamp":1760107816000},"page":"9865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Beyond Opioids: A Review of Suzetrigine for Acute Pain Management"],"prefix":"10.3390","volume":"26","author":[{"given":"Andrew","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Stony Brook Hospital, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yep","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Stony Brook Hospital, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Wozniak","sequence":"additional","affiliation":[{"name":"Renaissance School of Medicine, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha","family":"Javvaji","sequence":"additional","affiliation":[{"name":"Renaissance School of Medicine, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0117-9108","authenticated-orcid":false,"given":"Eman","family":"Nada","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Stony Brook Hospital, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-5908","authenticated-orcid":false,"given":"Sergio","family":"Bergese","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Stony Brook Hospital, Stony Brook, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.5114\/ait.2020.94756","article-title":"The opioid crisis in North America: Facts and future lessons for Europe","volume":"52","author":"Ayoo","year":"2020","journal-title":"Anaesthesiol. Intensive Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2105\/AJPH.2007.131714","article-title":"The promotion and marketing of oxycontin: Commercial triumph, public health tragedy","volume":"99","year":"2009","journal-title":"Am. J. Public Health"},{"key":"ref_3","unstructured":"CDC (2025, August 18). Understanding the Opioid Overdose Epidemic. Overdose Prevention, Available online: https:\/\/www.cdc.gov\/overdose-prevention\/about\/understanding-the-opioid-overdose-epidemic.html."},{"key":"ref_4","unstructured":"Tefera, L., and Lehrman, W. (2025, August 18). The HCAHPS Survey, Pain Management, and Opioid Misuse. The CMS Perspective: Clarifying Facts, Myths, and Approaches. Presentation Slides. Available online: https:\/\/www.qualityreportingcenter.com\/en\/inpatient-quality-reporting-programs\/hospital-value-based-purchasing-vbp-program\/vbp-archived-events\/vbp-event32\/."},{"key":"ref_5","unstructured":"Ahmad, F., Cisewski, J., Rossen, L., and Sutton, P. (2025, August 18). Products-Vital Statistics Rapid Release-Provisional Drug Overdose Data, Available online: https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/drug-overdose-data.htm."},{"key":"ref_6","unstructured":"FDA (2025, August 18). Commissioner of the FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s40122-024-00697-0","article-title":"Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective NaV1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain","volume":"14","author":"Osteen","year":"2025","journal-title":"Pain Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1152\/physrev.00052.2017","article-title":"The Role of Voltage-Gated Sodium Channels in Pain Signaling","volume":"99","author":"Bennett","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1172\/JCI42843","article-title":"Nociceptors: The sensors of the pain pathway","volume":"120","author":"Dubin","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Liu, S., and Kelliher, L. (2022). Physiology of pain\u2014A narrative review on the pain pathway and its application in the pain management. Dig. Med. Res., 5.","DOI":"10.21037\/dmr-21-100"},{"key":"ref_11","first-page":"33","article-title":"Extreme Ends of Pain Sensitivity in SCN9A Mutation Variants: Case Report and Literature Review","volume":"15","author":"Majeed","year":"2018","journal-title":"Innov. Clin. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/9195","article-title":"The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways","volume":"2","author":"Akopian","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wood, J.N., Yan, N., Huang, J., Zhao, J., Akopian, A., Cox, J.J., Woods, C.G., and Nassar, M.A. (2025). Sensory neuron sodium channels as pain targets; from cocaine to Journavx (VX-548, suzetrigine). J. Gen. Physiol., 157.","DOI":"10.1085\/jgp.202513778"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1124\/molpharm.124.000944","article-title":"State-Dependent Inhibition of Nav1.8 Sodium Channels by VX-150 and VX-548","volume":"106","author":"Vaelli","year":"2024","journal-title":"Mol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zeng, X., Powell, R., and Woolf, C.J. (2025). Mechanism-based nonopioid analgesic targets. J. Clin. Investig., 135.","DOI":"10.1172\/JCI191346"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jones, M., Demery, A., and Al-Horani, R.A. (2025). Suzetrigine: A Novel Non-Opioid Analgesic for Acute Pain Management\u2014A Review. Drugs Drug Candidates, 4.","DOI":"10.3390\/ddc4030032"},{"key":"ref_17","first-page":"1085","article-title":"Suzetrigine, a Nonopioid NaV1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials","volume":"142","author":"Bertoch","year":"2025","journal-title":"Anesthesiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.2147\/JPR.S509144","article-title":"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","volume":"18","author":"McCoun","year":"2025","journal-title":"J. Pain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.tips.2025.02.008","article-title":"Suzetrigine for moderate to severe acute pain","volume":"46","author":"Cho","year":"2025","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_20","unstructured":"FDA (2025, August 18). Journavx Product Quality Review, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2025\/219209Orig1s000ChemR.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa2209870","article-title":"Selective Inhibition of NaV1.8 with VX-548 for Acute Pain","volume":"389","author":"Jones","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_22","unstructured":"FDA (2025, August 18). Journavx Full Prescribing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/219209s000lbl.pdf."},{"key":"ref_23","unstructured":"FDA (2025, August 18). Journavx Integrated Review, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2025\/219209Orig1s000IntegratedR.pdf."},{"key":"ref_24","unstructured":"Vertex Pharmaceuticals Incorporated (2025, August 18). A Phase 1, Randomized, Double-Blind, Placebo- and Active-Controlled, Thorough QT;QTc Study of VX-548 in Healthy Subjects, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05818852."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/bja\/aet127","article-title":"Sex differences in pain: A brief review of clinical and experimental findings","volume":"111","author":"Bartley","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1177\/1071100717723132","article-title":"Ankle Block vs Single-Shot Popliteal Fossa Block as Primary Anesthesia for Forefoot Operative Procedures: Prospective, Randomized Comparison","volume":"38","author":"Schipper","year":"2017","journal-title":"Foot Ankle Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"i69","DOI":"10.1093\/bja\/aeq323","article-title":"When does acute pain become chronic?","volume":"105","author":"Voscopoulos","year":"2010","journal-title":"Br. J. Anaesth."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1213\/ANE.0000000000007721","article-title":"Suzetrigine-Induced Metabolism of Factor Xa Inhibitors May Increase Risk of Thrombosis in Perioperative and Pain Patients","volume":"141","author":"McCoy","year":"2025","journal-title":"Anesth. Analg."},{"key":"ref_29","unstructured":"Vertex Pharmaceuticals Incorporated (2025, August 18). A Phase 3, Open-Label Study Evaluating the Long-Term Safety and Effectiveness of Suzetrigine in Subjects with Pain Associated with Diabetic Peripheral Neuropathy, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06696443."},{"key":"ref_30","unstructured":"Vertex Pharmaceuticals Incorporated (2025, August 18). A Phase 4, Open-Label, Single-Arm Study Evaluating the Effectiveness and Safety of Suzetrigine as Part of Multimodal Therapy for Acute Pain After Aesthetic or Reconstructive Surgeries, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06887972."},{"key":"ref_31","unstructured":"Vertex Pharmaceuticals Incorporated (2025, August 18). A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Study of the Efficacy and Safety of VX-548 in Subjects with Painful Lumbosacral Radiculopathy, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06176196?utm_source=chatgpt.com."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/9865\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:01:35Z","timestamp":1760108495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/9865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":31,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26209865"],"URL":"https:\/\/doi.org\/10.3390\/ijms26209865","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]}}}