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Efficacy of Sodium Channel-Selective Analgesics in Postoperative, Neuralgia, and Neuropathy-Related Pain Management: A Systematic Review and Literature Review

. 2025 Mar 10 ; 26 (6) : . [epub] 20250310

Language English Country Switzerland Media electronic

Document type Systematic Review, Journal Article, Review

Postoperative pain is a prevalent problem, often lasting from days to years. To minimize opioid use and associated risks of dependency, Enhanced Recovery After Surgery (ERAS) protocols increasingly incorporate multimodal analgesics. Sodium channel-selective blockers are a promising non-opioid alternative, yet their application in postoperative pain remains underexplored. This systematic review evaluates their efficacy in managing postoperative, neuropathic, and neuralgia-related pain. A systematic review was conducted using controlled keywords across multiple databases to identify studies on sodium channel-selective blockers published up to 2024. Eligible studies included clinical trials, observational studies, case series, and reports involving patients aged 18 or older. Data were extracted on therapeutic outcomes, dosages, complications, and comparisons with other analgesics. Five studies met the inclusion criteria, involving 804 patients, 81.58% of whom were women. One study addressed postoperative pain, while the remaining five focused on neuropathy- and neuralgia-related pain. All studies reported significant pain reduction in at least one treatment group compared with placebo. In the study on postoperative pain, the sodium channel-selective blocker significantly reduced pain scores without requiring opioid analgesia. Across all studies, only two patients needed concomitant opioid therapy, and one discontinued treatment due to adverse effects. Dosages varied, with no reports of severe complications. Comparative analyses showed that sodium channel-selective blockers were as effective, if not superior, to traditional pain medications in reducing pain intensity. Sodium channel-selective blockers demonstrate significant potential in pain management with minimal opioid reliance. While effective for neuropathic pain, further studies are essential to validate their role in acute postoperative settings and refine their use in multimodal analgesia regimens.

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Gabriel R.A., Swisher M.W., Sztain J.F., Furnish T.J., Ilfeld B.M., Said E.T. State of the art opioid-sparing strategies for post-operative pain in adult surgical patients. Expert Opin. Pharmacother. 2019;20:949–961. doi: 10.1080/14656566.2019.1583743. PubMed DOI

Brummett C.M., Waljee J.F., Goesling J., Moser S., Lin P., Englesbe M.J., Bohnert A.S.B., Kheterpal S., Nallamothu B.K. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. JAMA Surg. 2017;152:e170504. doi: 10.1001/jamasurg.2017.0504. PubMed DOI PMC

Opioids. [(accessed on 10 October 2024)];2024 Available online: https://nida.nih.gov/research-topics/opioids.

Naftalovich R., Singal A., Iskander A.J. Enhanced Recovery After Surgery (ERAS) protocols for spine surgery—Review of literature. Anaesthesiol. Intensiv. Ther. 2022;54:71–79. doi: 10.5114/ait.2022.113961. PubMed DOI PMC

Barr L.F., Boss M.J., Mazzeffi M.A., Taylor B.S., Salenger R. Postoperative Multimodal Analgesia in Cardiac Surgery. Crit. Care Clin. 2020;36:631–651. doi: 10.1016/j.ccc.2020.06.003. PubMed DOI

Stumpo V., Staartjes V.E., Quddusi A., Corniola M.V., Tessitore E., Schröder M.L., Anderer E.G., Stienen M.N., Serra C., Regli L. Enhanced Recovery After Surgery strategies for elective craniotomy: A systematic review. J. Neurosurg. 2021;135:1857–1881. doi: 10.3171/2020.10.JNS203160. PubMed DOI

King J.D., Cautivar K., Tran D.A., Schmidt N., McSkane M., Pak E., Tran D.A., Ali M.M. The Impact of Non-opioid Analgesic Usage on Total Opioid Load During Traumatic Brain Injury Rehabilitation: A Retrospective Study. Cureus. 2023;15:e46872. doi: 10.7759/cureus.46872. PubMed DOI PMC

Wick E.C., Grant M.C., Wu C.L. Postoperative Multimodal Analgesia Pain Management With Nonopioid Analgesics and Techniques: A Review. JAMA Surg. 2017;152:691–697. doi: 10.1001/jamasurg.2017.0898. PubMed DOI

Alsaloum M., Higerd G.P., Effraim P.R., Waxman S.G. Status of peripheral sodium channel blockers for non-addictive pain treatment. Nat. Rev. Neurol. 2020;16:689–705. doi: 10.1038/s41582-020-00415-2. PubMed DOI

Black J.A., Frézel N., Dib-Hajj S.D., Waxman S.G. Expression of NaV1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn. Mol. Pain. 2012;8:82. doi: 10.1186/1744-8069-8-82. PubMed DOI PMC

Mueller A., Starobova H., Morgan M., Dekan Z., Cheneval O., Schroeder C.I., Alewood P.F., Deuis J.R., Vetter I. Antiallodynic effects of the selective NaV1.7 inhibitor Pn3a in a mouse model of acute postsurgical pain: Evidence for analgesic synergy with opioids and baclofen. Pain. 2019;160:1766–1780. doi: 10.1097/j.pain.0000000000001567. PubMed DOI

MacDonald D.I., Sikandar S., Weiss J., Pyrski M., Luiz A.P., Millet Q., Emery E.C., Mancini F., Iannetti G.D., Alles S.R., et al. A central mechanism of analgesia in mice and humans lacking the sodium channel Na(V)1.7. Neuron. 2021;109:1497–1512.e6. doi: 10.1016/j.neuron.2021.03.012. PubMed DOI PMC

Mulcahy J.V., Pajouhesh H., Beckley J.T., Delwig A., Du Bois J., Hunter J.C. Challenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform Na(V)1.7. J. Med. Chem. 2019;62:8695–8710. doi: 10.1021/acs.jmedchem.8b01906. PubMed DOI PMC

Joshi G.P., Kehlet H. Postoperative pain management in the era of ERAS: An overview. Best Pract. Res. Clin. Anaesthesiol. 2019;33:259–267. doi: 10.1016/j.bpa.2019.07.016. PubMed DOI

Simpson J.C., Bao X., Agarwala A. Pain Management in Enhanced Recovery after Surgery (ERAS) Protocols. Clin. Colon Rectal Surg. 2019;32:121–128. doi: 10.1055/s-0038-1676477. PubMed DOI PMC

Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Syst. Rev. 2021;10:89. doi: 10.1186/s13643-021-01626-4. PubMed DOI PMC

Babineau J. Product review: Covidence (systematic review software) J. Can. Health Libr. Assoc./J. L’association Bibliothèques Santé Can. 2014;35:68–71. doi: 10.5596/c14-016. DOI

Study Quality Assessment Tools. [(accessed on 10 October 2024)];2021 Available online: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools.

Estela-Zape J.L., Pizarro-Loaiza M.L., Arteaga G., Castaño S., Fierro L. Metabolites derived from medicinal plants modulating voltage-gated sodium channel activity: A systematic review. Phytomed. Plus. 2024;5:100724. doi: 10.1016/j.phyplu.2024.100724. DOI

Aman Y. Targeting cartilage sodium channels for osteoarthritis treatment. Nat. Aging. 2024;4:168. doi: 10.1038/s43587-024-00580-9. PubMed DOI

Da Silva J.L.V., Leite Á.I., Ferreira E.N., Da Silva F.M., Pavin J.P., Oliveira L.C., Leite M.E., De Araújo M.V., Ferreira R.N., Lamares R.J.T.C., et al. Gamma-Linolenic Acid Interactions with the Human Voltage-Gated Sodium Channel 1.7 by Molecular Docking: Its Role in the Action Mechanism on Mastalgia. IOSR J. Pharm. Biol. Sci. 2023;18:33–37.

Deng L., Dourado M., Reese R.M., Huang K., Shields S.D., Stark K.L., Maksymetz J., Lin H., Kaminker J.S., Jung M., et al. NaV1.7 is essential for nociceptor action potentials in the mouse in a manner independent of endogenous opioids. Neuron. 2023;111:2642–2659.e13. doi: 10.1016/j.neuron.2023.05.024. PubMed DOI

Kaye A.D., Everett E.S., Lehuquet A.M., Mason J.W., Maitski R., Plessala M.J., Barrie S., Baptiste C.J., Mychaskiw G., Ahmadzadeh S., et al. Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review. Curr. Pain Headache Rep. 2024;28:1135–1143. doi: 10.1007/s11916-024-01295-7. PubMed DOI

Lv M.D., Wei Y.X., Chen J.P., Cao M.Y., Wang Q.L., Hu S. Melatonin attenuated chronic visceral pain by reducing NaV1.8 expression and nociceptive neuronal sensitization. Mol. Pain. 2023;19:17448069231170072. doi: 10.1177/17448069231170072. PubMed DOI PMC

Maruta T., Kouroki S., Kurogi M., Hidaka K., Koshida T., Miura A., Nakagawa H., Yanagita T., Takeya R., Tsuneyoshi I. Comparison of Nocifensive Behavior in Na1.7–, Na1.8–, and Na1.9–Channelrhodopsin-2 Mice by Selective Optogenetic Activation of Targeted Sodium Channel Subtype-Expressing Afferents. J. Neurosci. Res. 2024;102:e25386. doi: 10.1002/jnr.25386. PubMed DOI

Yamaguchi T., Okada T., Kimura T. Functional expression of the chimera proteins of NaV1.7 and NavAb in Escherichia coli. Protein Expr. Purif. 2024;226:106615. doi: 10.1016/j.pep.2024.106615. PubMed DOI

Mai Y., Flechsig J., Warr J., Hummel T. Responses to the activation of different intranasal trigeminal receptors: Evidence from behavioral, peripheral and central levels. Behav. Brain Res. 2024;480:115371. doi: 10.1016/j.bbr.2024.115371. PubMed DOI

Engel P., Zhou F., Tran B.T.T., Schmidtko A., Lu R. Slick potassium channels limit TRPM3-mediated activation of sensory neurons. Front. Pharmacol. 2024;15:1459735. doi: 10.3389/fphar.2024.1459735. PubMed DOI PMC

Kumamoto E. Anesthetic- and Analgesic-Related Drugs Modulating Both Voltage-Gated Na(+) and TRP Channels. Biomolecules. 2024;14:1619. doi: 10.3390/biom14121619. PubMed DOI PMC

Liu X., Jiang X., Liu Z., Chen F., Chen J., Chu X., Bu W., Liu Y. Neuron Modulation by Synergetic Management of Redox Status and Oxidative Stress. Small. 2025;21:e2408494. doi: 10.1002/smll.202408494. PubMed DOI

Chantadul V., Rotpenpian N., Arayapisit T., Wanasuntronwong A. Transient receptor potential channels in dental inflammation and pain perception: A comprehensive review. Heliyon. 2025;11:e41730. doi: 10.1016/j.heliyon.2025.e41730. PubMed DOI PMC

Sankaranarayanan I., Kume M., Mohammed A., Mwirigi J.M., Inturi N.N., Munro G., Petersen K.A., Tavares-Ferreira D., Price T.J. Persistent changes in the dorsal root ganglion nociceptor translatome governs hyperalgesic priming in mice: Roles of GPR88 and Meteorin. Pain. 2025 doi: 10.1097/j.pain.0000000000003523. PubMed DOI

An Y., Zhang J., Ren Q., Liu J., Liu Z., Cao K. The Mechanism of Acupuncture Therapy for Migraine: A Systematic Review of Animal Studies on Rats. J. Pain Res. 2025;18:473–487. doi: 10.2147/JPR.S504892. PubMed DOI PMC

Sousa F.S.S., Baldinotti R., Fronza M.G., Balaguez R., Alves D., Brüning C.A., Savegnago L. Exploring the therapeutic potential of α-(Phenylselanyl) acetophenone in tumor necrosis Factor-α-Induced depressive-like and hyperalgesic behavior in mice. Brain Res. 2025;1851:149473. doi: 10.1016/j.brainres.2025.149473. PubMed DOI

Qian J.-L., Wang J., Shen Z.-Y., Xu B.-Q., Shen D.-P., Yang C. Effect of nalbuphine on analgesia and pain factors after gastric cancer resection. World J. Gastrointest. Surg. 2025;17:99327. doi: 10.4240/wjgs.v17.i1.99327. PubMed DOI PMC

Choi S.-H., Kim Y.-M., Son J.-Y., Ahn D.-K. Microiontophoretic Application of Dynorphin in Dental Pain: Excitatory or Inhibitory Effects. J. Pain Res. 2025;18:455–464. doi: 10.2147/JPR.S499040. PubMed DOI PMC

Wang J., Zhang N., Liu H.Z., Wang J.L., Zhang Y.B., Su D.D., Miao J. Hydrogen Sulfide (H(2)S) Generated in the Colon Induces Neuropathic Pain by Activating Spinal NMDA Receptors in a Rodent Model of Chronic Constriction Injury. Neurochem. Res. 2025;50:90. doi: 10.1007/s11064-025-04342-w. PubMed DOI

Hung K.-C., Liu W.-C., Hsu C.-W., Wu J.-Y., Liao S.-W., Chen I.-W. Efficacy of Erector Spinae Plane Block on Analgesic Outcomes in Patients Undergoing Metabolic Surgery: A Meta-Analysis of Randomized Controlled Trials. Obes. Surg. 2025:1–11. doi: 10.1007/s11695-025-07724-9. PubMed DOI

García-Domínguez M. A Comprehensive Analysis of Fibromyalgia and the Role of the Endogenous Opioid System. Biomedicines. 2025;13:165. doi: 10.3390/biomedicines13010165. PubMed DOI PMC

de Greef B.T., Hoeijmakers J.G., Geerts M., Oakes M., Church T.J., Waxman S.G., Merkies I.S. Lacosamide in patients with NaV1.7 mutations-related small fibre neuropathy: A randomized controlled trial. Brain. 2019;142:263–275. doi: 10.1093/brain/awy329. PubMed DOI

Faber C.G., Attal N., Lauria G., Dworkin R.H., Freeman R., Dawson K.T., Finnigan H., Hajihosseini A., Naik H., Serenko M., et al. Efficacy and safety of vixotrigine in idiopathic or diabetes-associated painful small fibre neuropathy (CONVEY): A phase 2 placebo-controlled enriched-enrolment randomised withdrawal study. eClinicalMedicine. 2023;59:101971. doi: 10.1016/j.eclinm.2023.101971. PubMed DOI PMC

Jones J., Correll D.J., Lechner S.M., Jazic I., Miao X., Shaw D., White P.F. Selective Inhibition of Na(V)1.8 with VX-548 for Acute Pain. N. Engl. J. Med. 2023;389:393–405. doi: 10.1056/NEJMoa2209870. PubMed DOI

Maihöfner C., Schneider S., Bialas P., Gockel H., Beer K.-G., Bartels M., Kern K.-U. Successful treatment of complex regional pain syndrome with topical ambroxol: A case series. Pain Manag. 2018;8:427–436. doi: 10.2217/pmt-2018-0048. PubMed DOI

Zakrzewska J.M., Palmer J., Morisset V., Giblin G.M., Obermann M., Ettlin D.A., Cruccu G., Bendtsen L., Estacion M., Derjean D., et al. Safety and efficacy of a NaV1.7 selective sodium channel blocker in patients with trigeminal neuralgia: A double-blind, placebo-controlled, randomised withdrawal phase 2a trial. Lancet Neurol. 2017;16:291–300. doi: 10.1016/S1474-4422(17)30005-4. PubMed DOI

Adewumi A.D., Hollingworth S.A., Maravilla J.C., Connor J.P., Alati R. Prescribed Dose of Opioids and Overdose: A Systematic Review and Meta-Analysis of Unintentional Prescription Opioid Overdose. CNS Drugs. 2018;32:101–116. doi: 10.1007/s40263-018-0499-3. PubMed DOI

Crystal D.T.B., Blankensteijn L.L., Ibrahim A.M.S.M., Brownstein G.M., Reed L.S., Watts D.C., Lin S.J.M. Quantifying the Crisis: Opioid-Related Adverse Events in Outpatient Ambulatory Plastic Surgery. Plast. Reconstr. Surg. 2020;145:687–695. doi: 10.1097/PRS.0000000000006570. PubMed DOI

Hart A.M., Broecker J.S., Kao L., Losken A. Opioid Use following Outpatient Breast Surgery: Are Physicians Part of the Problem? Plast. Reconstr. Surg. 2018;142:611–620. doi: 10.1097/PRS.0000000000004636. PubMed DOI

Fairley M., Humphreys K., Joyce V.R., Bounthavong M., Trafton J., Combs A., Oliva E.M., Goldhaber-Fiebert J.D., Asch S.M., Brandeau M.L., et al. Cost-effectiveness of Treatments for Opioid Use Disorder. JAMA Psychiatry. 2021;78:767–777. doi: 10.1001/jamapsychiatry.2021.0247. PubMed DOI PMC

Cooney M., Quinlan-Colwell A. Assessment and Multimodal Management of Pain: An Integrative Approach. Elsevier Health Sciences; Amsterdam, The Netherlands: 2020.

Memtsoudis S.G., Poeran J., Zubizarreta N., Cozowicz C., Mörwald E.E., Mariano E.R., Mazumdar M. Association of Multimodal Pain Management Strategies with Perioperative Outcomes and Resource Utilization: A Population-based Study. Anesthesiology. 2018;128:891–902. doi: 10.1097/ALN.0000000000002132. PubMed DOI

Cozowicz C., Olson A., Poeran J., Mörwald E.E., Zubizarreta N., Girardi F.P., Hughes A.P., Mazumdar M., Memtsoudis S.G. Opioid prescription levels and postoperative outcomes in orthopedic surgery. Pain. 2017;158:2422–2430. doi: 10.1097/j.pain.0000000000001047. PubMed DOI

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