{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:56:08Z","timestamp":1792605368544,"version":"4.5.0"},"reference-count":94,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["CNS Drugs"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1007\/s40263-026-01272-1","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T13:52:51Z","timestamp":1771681971000},"page":"523-534","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["TRPV1 Receptor Modulators: Emerging Therapies for Neuropathic, Osteoarthritic, and Perioperative Pain"],"prefix":"10.1007","volume":"40","author":[{"given":"Edward H.","family":"Tsai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5506-398X","authenticated-orcid":false,"given":"Tong J.","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"issue":"6653","key":"1272_CR1","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/39807","volume":"389","author":"MJ Caterina","year":"1997","unstructured":"Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389(6653):816\u201324.","journal-title":"Nature"},{"key":"1272_CR2","unstructured":"Ernfors P AEM, Svenningsson P. Scientific background: discoveries of receptors for temperature and touch. NobelPrize.org; 2021. https:\/\/www.nobelprize.org\/prizes\/medicine\/2021\/advanced-information\/. Accessed 13 Aug 2025."},{"issue":"3","key":"1272_CR3","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/S0896-6273(00)80564-4","volume":"21","author":"M Tominaga","year":"1998","unstructured":"Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998;21(3):531\u201343.","journal-title":"Neuron"},{"key":"1272_CR4","doi-asserted-by":"crossref","unstructured":"Atawala NAV, Kalava A. TRPV1 modulation: a \u201cspicy\u201d approach to pain relief. ASRA Pain Medicine News. 2023;48.","DOI":"10.52211\/ASRA110123.006"},{"issue":"1","key":"1272_CR5","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00424-005-1457-8","volume":"451","author":"M Tominaga","year":"2005","unstructured":"Tominaga M, Tominaga T. Structure and function of TRPV1. Pflugers Arch. 2005;451(1):143\u201350.","journal-title":"Pflugers Arch"},{"key":"1272_CR6","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1146\/annurev-cellbio-101011-155833","volume":"29","author":"D Julius","year":"2013","unstructured":"Julius D. TRP channels and pain. Annu Rev Cell Dev Biol. 2013;29:355\u201384.","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"3","key":"1272_CR7","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1517\/14728222.11.3.307","volume":"11","author":"W Ma","year":"2007","unstructured":"Ma W, Quirion R. Inflammatory mediators modulating the transient receptor potential vanilloid 1 receptor: therapeutic targets to treat inflammatory and neuropathic pain. Expert Opin Ther Targets. 2007;11(3):307\u201320.","journal-title":"Expert Opin Ther Targets"},{"issue":"1","key":"1272_CR8","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1523\/JNEUROSCI.4901-08.2009","volume":"29","author":"A Dhaka","year":"2009","unstructured":"Dhaka A, Uzzell V, Dubin AE, Mathur J, Petrus M, Bandell M, et al. TRPV1 is activated by both acidic and basic pH. J Neurosci. 2009;29(1):153\u20138.","journal-title":"J Neurosci"},{"issue":"6","key":"1272_CR9","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1016\/j.celrep.2017.10.063","volume":"21","author":"Y Nersesyan","year":"2017","unstructured":"Nersesyan Y, Demirkhanyan L, Cabezas-Bratesco D, Oakes V, Kusuda R, Dawson T, et al. Oxytocin modulates nociception as an agonist of pain-sensing TRPV1. Cell Rep. 2017;21(6):1681\u201391.","journal-title":"Cell Rep"},{"key":"1272_CR10","volume-title":"TRP ion channel function in sensory transduction and cellular signaling cascades. Frontiers in Neuroscience","author":"T Rosenbaum","year":"2007","unstructured":"Rosenbaum T, Simon SA. TRPV1 receptors and signal transduction. In: Liedtke WB, Heller S, editors. TRP ion channel function in sensory transduction and cellular signaling cascades. Frontiers in Neuroscience. Boca Raton: CRC Press\/Taylor & Francis; 2007."},{"issue":"2","key":"1272_CR11","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S0031-6997(24)01403-0","volume":"51","author":"A Szallasi","year":"1999","unstructured":"Szallasi A, Blumberg PM. Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev. 1999;51(2):159\u2013212.","journal-title":"Pharmacol Rev"},{"issue":"1-2","key":"1272_CR12","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.molbrainres.2004.12.003","volume":"135","author":"A Toth","year":"2005","unstructured":"Toth A, Boczan J, Kedei N, Lizanecz E, Bagi Z, Papp Z, et al. Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat brain. Brain Res Mol Brain Res. 2005;135(1\u20132):162\u20138.","journal-title":"Brain Res Mol Brain Res"},{"key":"1272_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01064","volume":"10","author":"Q Du","year":"2019","unstructured":"Du Q, Liao Q, Chen C, Yang X, Xie R, Xu J. The role of transient receptor potential vanilloid 1 in common diseases of the digestive tract and the cardiovascular and respiratory system. Front Physiol. 2019;10:1064.","journal-title":"Front Physiol"},{"issue":"1","key":"1272_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-79271-9","volume":"14","author":"Y Jin","year":"2024","unstructured":"Jin Y, Brennecke J, Sodmann A, Blum R, Sommer C. Antibody selection and automated quantification of TRPV1 immunofluorescence on human skin. Sci Rep. 2024;14(1):28496.","journal-title":"Sci Rep"},{"key":"1272_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.870952","volume":"13","author":"T Xiao","year":"2022","unstructured":"Xiao T, Sun M, Kang J, Zhao C. Transient receptor potential vanilloid1 (TRPV1) channel opens sesame of T cell responses and T cell-mediated inflammatory diseases. Front Immunol. 2022;13:870952.","journal-title":"Front Immunol"},{"key":"1272_CR16","first-page":"3","volume-title":"Turning up the heat on pain: TRPVI receptors in pain and inflammation","author":"J Szolcsanyi","year":"2005","unstructured":"Szolcsanyi J. Hot peppers, pain and analgesics. In: Malmberg AB, Bley KR, editors. Turning up the heat on pain: TRPVI receptors in pain and inflammation. 1st ed. Basel, Boston: Birkhauser Verlag; 2005. p. 3\u201322.","edition":"1"},{"issue":"23","key":"1272_CR17","doi-asserted-by":"publisher","first-page":"6436","DOI":"10.1016\/j.cell.2025.07.048","volume":"188","author":"L Yuan","year":"2025","unstructured":"Yuan L, Chandel NS, Julius D. Mitochondrial activity tunes nociceptor resilience to excitotoxicity. Cell. 2025;188(23):6436-52.e18.","journal-title":"Cell"},{"issue":"21","key":"1272_CR18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262110350","volume":"26","author":"G Jancso","year":"2025","unstructured":"Jancso G, Dux M, Santha P. Morphological correlates of TRPV1 agonist-induced activation and defunctionalization of nociceptor neurons. Int J Mol Sci. 2025;26(21):10350.","journal-title":"Int J Mol Sci"},{"issue":"4","key":"1272_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/ph9040066","volume":"9","author":"MK Chung","year":"2016","unstructured":"Chung MK, Campbell JN. Use of capsaicin to treat pain: mechanistic and therapeutic considerations. Pharmaceuticals (Basel). 2016;9(4):66.","journal-title":"Pharmaceuticals (Basel)"},{"issue":"1","key":"1272_CR20","first-page":"6","volume":"1","author":"A Szallasi","year":"1996","unstructured":"Szallasi A. Vanilloid-sensitive neurons: a fundamental subdivision of the peripheral nervous system. J Peripher Nerv Syst. 1996;1(1):6\u201318.","journal-title":"J Peripher Nerv Syst"},{"issue":"7","key":"1272_CR21","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21070844","volume":"21","author":"V Fattori","year":"2016","unstructured":"Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA. Capsaicin: current understanding of its mechanisms and therapy of pain and other pre-clinical and clinical uses. Molecules. 2016;21(7):844.","journal-title":"Molecules"},{"issue":"2","key":"1272_CR22","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3390\/cells3020517","volume":"3","author":"R Brito","year":"2014","unstructured":"Brito R, Sheth S, Mukherjea D, Rybak LP, Ramkumar V. TRPV1: a potential drug target for treating various diseases. Cells. 2014;3(2):517\u201345.","journal-title":"Cells"},{"issue":"9","key":"1272_CR23","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1517\/13543784.2012.704021","volume":"21","author":"A Szallasi","year":"2012","unstructured":"Szallasi A, Sheta M. Targeting TRPV1 for pain relief: limits, losers and laurels. Expert Opin Investig Drugs. 2012;21(9):1351\u201369.","journal-title":"Expert Opin Investig Drugs"},{"key":"1272_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2024.102447","volume":"75","author":"AP Koivisto","year":"2024","unstructured":"Koivisto AP, Voets T, Iadarola MJ, Szallasi A. Targeting trp channels for pain relief: a review of current evidence from bench to bedside. Curr Opin Pharmacol. 2024;75:102447.","journal-title":"Curr Opin Pharmacol"},{"key":"1272_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.122954","volume":"355","author":"MM Rahman","year":"2024","unstructured":"Rahman MM, Jo YY, Kim YH, Park CK. Current insights and therapeutic strategies for targeting TRPV1 in neuropathic pain management. Life Sci. 2024;355:122954.","journal-title":"Life Sci"},{"issue":"1","key":"1272_CR26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s40265-020-01429-2","volume":"81","author":"M Iftinca","year":"2021","unstructured":"Iftinca M, Defaye M, Altier C. TRPV1-targeted drugs in development for human pain conditions. Drugs. 2021;81(1):7\u201327.","journal-title":"Drugs"},{"issue":"11","key":"1272_CR27","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1016\/j.neuron.2024.02.016","volume":"112","author":"YZ Huang","year":"2024","unstructured":"Huang YZ, Ma JX, Bian YJ, Bai QR, Gao YH, Di SK, et al. TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception. Neuron. 2024;112(11):1815-31.e4.","journal-title":"Neuron"},{"issue":"1","key":"1272_CR28","volume":"1","author":"S Derry","year":"2017","unstructured":"Derry S, Rice AS, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;1(1):CD007393.","journal-title":"Cochrane Database Syst Rev"},{"key":"1272_CR29","doi-asserted-by":"crossref","unstructured":"Ann J, Blumberg P, Lee J. TRPV1 antagonists: future drug discovery directions. In: Szallasi, A. TRP Channels as Therapeutic Targets (Second Edition). London: Academic Press; 2024. pp. 163\u201383.","DOI":"10.1016\/B978-0-443-18653-0.00022-8"},{"issue":"9","key":"1272_CR30","volume":"2012","author":"S Derry","year":"2012","unstructured":"Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2012;2012(9):CD010111.","journal-title":"Cochrane Database Syst Rev"},{"issue":"1","key":"1272_CR31","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1212\/WNL.0000000000013038","volume":"98","author":"R Price","year":"2022","unstructured":"Price R, Smith D, Franklin G, Gronseth G, Pignone M, David WS, et al. Oral and topical treatment of painful diabetic polyneuropathy: practice guideline update summary: report of the AAN Guideline Subcommittee. Neurology. 2022;98(1):31\u201343.","journal-title":"Neurology"},{"issue":"3","key":"1272_CR32","first-page":"226","volume":"109","author":"S Bragg","year":"2024","unstructured":"Bragg S, Marrison ST, Haley S. Diabetic peripheral neuropathy: prevention and treatment. Am Fam Physician. 2024;109(3):226\u201332.","journal-title":"Am Fam Physician"},{"issue":"11","key":"1272_CR33","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","volume":"27","author":"RR Bannuru","year":"2019","unstructured":"Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthr Cartil. 2019;27(11):1578\u201389.","journal-title":"Osteoarthr Cartil"},{"issue":"2","key":"1272_CR34","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/art.41142","volume":"72","author":"SL Kolasinski","year":"2020","unstructured":"Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, et al. 2019 American College of Rheumatology\/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheumatol. 2020;72(2):220\u201333.","journal-title":"Arthritis Rheumatol"},{"key":"1272_CR35","unstructured":"Department of Veterans Affairs, Department of Defense. VA\/DoD clinical practice guideline for the non-surgical management of hip and knee osteoarthritis. 2020. https:\/\/www.healthquality.va.gov\/guidelines\/CD\/OA\/VADODOACPG.pdf. Accessed 22 Jan 2026."},{"issue":"10","key":"1272_CR36","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/cix636","volume":"65","author":"RD Bruce","year":"2017","unstructured":"Bruce RD, Merlin J, Lum PJ, Ahmed E, Alexander C, Corbett AH, et al. 2017 HIVMA of IDSA clinical practice guideline for the management of chronic pain in patients living with HIV. Clin Infect Dis. 2017;65(10):e1-37.","journal-title":"Clin Infect Dis"},{"issue":"2","key":"1272_CR37","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","volume":"14","author":"NB Finnerup","year":"2015","unstructured":"Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162\u201373.","journal-title":"Lancet Neurol"},{"key":"1272_CR38","unstructured":"National Institute for Health and Care Excellence. Neuropathic pain in adults: pharmacological management in non-specialist settings 2013 [updated September 22, 2020]. www.nice.org.uk\/guidance\/cg173. Accessed 22 Jan 2026."},{"key":"1272_CR39","unstructured":"Averitas Pharma I. Qutenza prescribing information. 2024."},{"issue":"6","key":"1272_CR40","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/j.jpainsymman.2009.11.316","volume":"39","author":"DM Simpson","year":"2010","unstructured":"Simpson DM, Gazda S, Brown S, Webster LR, Lu SP, Tobias JK, et al. Long-term safety of NGX-4010, a high-concentration capsaicin patch, in patients with peripheral neuropathic pain. J Pain Symptom Manage. 2010;39(6):1053\u201364.","journal-title":"J Pain Symptom Manage"},{"issue":"6","key":"1272_CR41","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.jpain.2009.09.019","volume":"11","author":"WR Kennedy","year":"2010","unstructured":"Kennedy WR, Vanhove GF, Lu SP, Tobias J, Bley KR, Walk D, et al. A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers. J Pain. 2010;11(6):579\u201387.","journal-title":"J Pain"},{"issue":"12","key":"1272_CR42","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/S1474-4422(08)70228-X","volume":"7","author":"M Backonja","year":"2008","unstructured":"Backonja M, Wallace MS, Blonsky ER, Cutler BJ, Malan JP, Rauck R, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008;7(12):1106\u201312.","journal-title":"Lancet Neurol"},{"issue":"1","key":"1272_CR43","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1111\/j.1526-4637.2010.01004.x","volume":"12","author":"GA Irving","year":"2011","unstructured":"Irving GA, Backonja MM, Dunteman E, Blonsky ER, Vanhove GF, Lu SP, et al. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Med. 2011;12(1):99\u2013109.","journal-title":"Pain Med"},{"issue":"1","key":"1272_CR44","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jpain.2016.09.008","volume":"18","author":"DM Simpson","year":"2017","unstructured":"Simpson DM, Robinson-Papp J, Van J, Stoker M, Jacobs H, Snijder RJ, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. J Pain. 2017;18(1):42\u201353.","journal-title":"J Pain"},{"issue":"1","key":"1272_CR45","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-016-0752-7","volume":"16","author":"AI Vinik","year":"2016","unstructured":"Vinik AI, Perrot S, Vinik EJ, Pazdera L, Jacobs H, Stoker M, et al. Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study. BMC Neurol. 2016;16(1):251.","journal-title":"BMC Neurol"},{"issue":"12","key":"1272_CR46","first-page":"388","volume":"2","author":"AI Vinik","year":"2019","unstructured":"Vinik AI, Perrot S, Vinik EJ, Pazdera L, Stoker M, Snijder RJ, et al. Repeat treatment with capsaicin 8% patch (179mg capsaicin cutaneous patch): effects on pain, quality of life, and patient satisfaction in painful diabetic peripheral neuropathy: an open-label, randomized controlled clinical trial. J Curr Med Res Opin. 2019;2(12):388\u2013401.","journal-title":"J Curr Med Res Opin."},{"issue":"4","key":"1272_CR47","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.clinthera.2017.02.010","volume":"39","author":"F van Nooten","year":"2017","unstructured":"van Nooten F, Treur M, Pantiri K, Stoker M, Charokopou M. Capsaicin 8% patch versus oral neuropathic pain medications for the treatment of painful diabetic peripheral neuropathy: a systematic literature review and network meta-analysis. Clin Ther. 2017;39(4):787-803.e18.","journal-title":"Clin Ther"},{"issue":"3","key":"1272_CR48","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2024-004864","volume":"13","author":"M Uberall","year":"2025","unstructured":"Uberall M, Quandel T, Engelen S, Garcia-Guerra L, Fajri T, Allen S, et al. CASPAR: a retrospective cohort study of the high-concentration capsaicin topical system in patients with painful diabetic peripheral neuropathy of the feet. BMJ Open Diabetes Res Care. 2025;13(3):e004864.","journal-title":"BMJ Open Diabetes Res Care"},{"issue":"24","key":"1272_CR49","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1212\/01.wnl.0000314647.35825.9c","volume":"70","author":"DM Simpson","year":"2008","unstructured":"Simpson DM, Brown S, Tobias J, Group N-CS. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology. 2008;70(24):2305\u201313.","journal-title":"Neurology"},{"issue":"2","key":"1272_CR50","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1097\/QAI.0b013e31823e31f7","volume":"59","author":"DB Clifford","year":"2012","unstructured":"Clifford DB, Simpson DM, Brown S, Moyle G, Brew BJ, Conway B, et al. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. J Acquir Immune Defic Syndr. 2012;59(2):126\u201333.","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"9","key":"1272_CR51","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1016\/j.pain.2013.04.044","volume":"154","author":"J Mou","year":"2013","unstructured":"Mou J, Paillard F, Turnbull B, Trudeau J, Stoker M, Katz NP. Efficacy of Qutenza\u00ae (capsaicin) 8% patch for neuropathic pain: a meta-analysis of the Qutenza Clinical Trials Database. Pain. 2013;154(9):1632\u20139.","journal-title":"Pain"},{"issue":"5","key":"1272_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/EBP.0000000000000259","volume":"22","author":"J Breen","year":"2019","unstructured":"Breen J, Schrubbe H, Smallwood S. Does topical capsaicin provide pain relief for patients suffering from chronic neuropathic pain? Evid Based Pract. 2019;22(5):1.","journal-title":"Evid Based Pract"},{"issue":"10","key":"1272_CR53","first-page":"656","volume":"96","author":"A Saguil","year":"2017","unstructured":"Saguil A, Kane S, Mercado M, Lauters R. Herpes zoster and postherpetic neuralgia: prevention and management. Am Fam Physician. 2017;96(10):656\u201363.","journal-title":"Am Fam Physician"},{"issue":"9","key":"1272_CR54","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1111\/j.1468-1331.2010.02999.x","volume":"17","author":"N Attal","year":"2010","unstructured":"Attal N, Cruccu G, Baron R, Haanpaa M, Hansson P, Jensen TS, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113-e88.","journal-title":"Eur J Neurol"},{"issue":"5","key":"1272_CR55","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S1474-4422(25)00068-7","volume":"24","author":"N Soliman","year":"2025","unstructured":"Soliman N, Moisset X, Ferraro MC, de Andrade DC, Baron R, Belton J, et al. Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis. Lancet Neurol. 2025;24(5):413\u201328.","journal-title":"Lancet Neurol"},{"issue":"11","key":"1272_CR56","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1080\/14656566.2020.1759550","volume":"21","author":"C Bonezzi","year":"2020","unstructured":"Bonezzi C, Costantini A, Cruccu G, Fornasari DMM, Guardamagna V, Palmieri V, et al. Capsaicin 8% dermal patch in clinical practice: an expert opinion. Expert Opin Pharmacother. 2020;21(11):1377\u201387.","journal-title":"Expert Opin Pharmacother"},{"issue":"2","key":"1272_CR57","doi-asserted-by":"publisher","DOI":"10.1097\/PR9.0000000000001235","volume":"10","author":"R Freynhagen","year":"2025","unstructured":"Freynhagen R, Baron R, Huygen F, Perrot S. Narrative review of the efficacy and safety of the high-concentration (179mg) capsaicin patch in peripheral neuropathic pain with recommendations for clinical practice and future research. PAIN Rep. 2025;10(2):e1235.","journal-title":"PAIN Rep"},{"key":"1272_CR58","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1452099","volume":"14","author":"MP Lux","year":"2024","unstructured":"Lux MP, Flother L, Fromter C, Rack B, Veselinovic K, Heine M, et al. Topical treatment of chemotherapy-induced peripheral neuropathy (CIPN) with high-concentration (179 mg) capsaicin patch in breast cancer patients: results of the QUCIP study. Front Oncol. 2024;14:1452099.","journal-title":"Front Oncol"},{"issue":"10","key":"1272_CR59","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/S0024-3205(96)00567-X","volume":"60","author":"G Appendino","year":"1997","unstructured":"Appendino G, Szallasi A. Euphorbium: modern research on its active principle, resiniferatoxin, revives an ancient medicine. Life Sci. 1997;60(10):681\u201396.","journal-title":"Life Sci"},{"issue":"20","key":"1272_CR60","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015042","volume":"24","author":"A Szallasi","year":"2023","unstructured":"Szallasi A. Resiniferatoxin: nature\u2019s precision medicine to silence TRPV1-positive afferents. Int J Mol Sci. 2023;24(20):15042.","journal-title":"Int J Mol Sci"},{"issue":"24","key":"1272_CR61","doi-asserted-by":"publisher","first-page":"5639","DOI":"10.1113\/JP279909","volume":"598","author":"TX Phan","year":"2020","unstructured":"Phan TX, Ton HT, Gulyas H, Porszasz R, Toth A, Russo R, et al. TRPV1 expressed throughout the arterial circulation regulates vasoconstriction and blood pressure. J Physiol. 2020;598(24):5639\u201359.","journal-title":"J Physiol"},{"key":"1272_CR62","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2023.1306180","volume":"17","author":"S Shehab","year":"2023","unstructured":"Shehab S, Javed H, Johnson AM, Tariq S, Kumar CA, Emerald BS. Unveiling the mechanisms of neuropathic pain suppression: perineural resiniferatoxin targets Trpv1 and beyond. Front Neuroanat. 2023;17:1306180.","journal-title":"Front Neuroanat"},{"key":"1272_CR63","doi-asserted-by":"crossref","unstructured":"Leong MS, Copenhaver D. Potent neurotoxins for cancer pain treatment: resiniferatoxin and saporin. In: Krames E, Peckham PH, Rezai AR, ScienceDirect, editors. Neuromodulation: comprehensive textbook of principles, technologies, and therapies. 2nd ed. London: Academic Press; 2018: p. 861\u20138.","DOI":"10.1016\/B978-0-12-805353-9.00069-3"},{"issue":"3","key":"1272_CR64","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16030648","volume":"16","author":"A Szallasi","year":"2024","unstructured":"Szallasi A. Targeting TRPV1 for cancer pain relief: can it work? Cancers (Basel). 2024;16(3):648.","journal-title":"Cancers (Basel)"},{"issue":"10","key":"1272_CR65","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1080\/17581869.2025.2535271","volume":"15","author":"MJ Iadarola","year":"2025","unstructured":"Iadarola MJ, Sapio MR, Nahama A, Mannes AJ. Intraarticular resiniferatoxin, a potent TRPV1 agonist, for treatment of osteoarthritic pain. Pain Manag. 2025;15(10):659\u201370.","journal-title":"Pain Manag"},{"key":"1272_CR66","unstructured":"Gr\u00fcnenthal. RTX (resiniferatoxin). R&D pipeline 2024 [updated August 22]. https:\/\/www.grunenthal.com\/en\/science\/pipeline\/rtx. Accessed 22 Jan 2026."},{"issue":"1","key":"1272_CR67","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neulet.2005.09.046","volume":"393","author":"L Menendez","year":"2006","unstructured":"Menendez L, Juarez L, Garcia E, Garcia-Suarez O, Hidalgo A, Baamonde A. Analgesic effects of capsazepine and resiniferatoxin on bone cancer pain in mice. Neurosci Lett. 2006;393(1):70\u20133.","journal-title":"Neurosci Lett"},{"key":"1272_CR68","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.705743","volume":"12","author":"MJ Iadarola","year":"2021","unstructured":"Iadarola MJ, Brown DC, Nahama A, Sapio MR, Mannes AJ. Pain treatment in the companion canine model to validate rodent results and incentivize the transition to human clinical trials. Front Pharmacol. 2021;12:705743.","journal-title":"Front Pharmacol"},{"issue":"6","key":"1272_CR69","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2400423","volume":"4","author":"AJ Mannes","year":"2025","unstructured":"Mannes AJ, Heiss JD, Berger A, Alewine CC, Butman JA, Hughes MS, et al. Treatment of intractable cancer pain with resiniferatoxin: an interim study. NEJM Evid. 2025;4(6):EVIDoa2400423.","journal-title":"NEJM Evid"},{"issue":"6","key":"1272_CR70","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDe2500094","volume":"4","author":"KB Shah","year":"2025","unstructured":"Shah KB, Dar B. Resiniferatoxin and the future of cancer pain management: a step forward? NEJM Evid. 2025;4(6):EVIDe2500094.","journal-title":"NEJM Evid"},{"key":"1272_CR71","unstructured":"Nedeljkovic SS, Narang S, Rickerson E, Levitt RC, Horn DB, Patin DL, et al., editors. A multicenter, open-label, phase 1b study to assess the safety and define the maximally tolerated dose of epidural resiniferatoxin (RTX) injection for treatment of intractable pain associated with cancer. 2020 Annual Meeting of the American Academy of Pain Medicine; 26 Feb\u20131 Mar 2020; National Harbor (MD)."},{"issue":"4","key":"1272_CR72","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1172\/JCI94331","volume":"128","author":"MR Sapio","year":"2018","unstructured":"Sapio MR, Neubert JK, LaPaglia DM, Maric D, Keller JM, Raithel SJ, et al. Pain control through selective chemo-axotomy of centrally projecting TRPV1+ sensory neurons. J Clin Investig. 2018;128(4):1657\u201370.","journal-title":"J Clin Investig"},{"issue":"14","key":"1272_CR73","doi-asserted-by":"publisher","first-page":"11021","DOI":"10.1074\/jbc.M008392200","volume":"276","author":"Z Olah","year":"2001","unstructured":"Olah Z, Szabo T, Karai L, Hough C, Fields RD, Caudle RM, et al. Ligand-induced dynamic membrane changes and cell deletion conferred by vanilloid receptor 1. J Biol Chem. 2001;276(14):11021\u201330.","journal-title":"J Biol Chem"},{"issue":"9","key":"1272_CR74","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1002\/art.40894","volume":"71","author":"RM Stevens","year":"2019","unstructured":"Stevens RM, Ervin J, Nezzer J, Nieves Y, Guedes K, Burges R, et al. Randomized, double-blind, placebo-controlled trial of intraarticular trans-capsaicin for pain associated with osteoarthritis of the knee. Arthritis Rheumatol. 2019;71(9):1524\u201333.","journal-title":"Arthritis Rheumatol"},{"issue":"4","key":"1272_CR75","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26040778","volume":"26","author":"JN Campbell","year":"2021","unstructured":"Campbell JN, Stevens R, Hanson P, Connolly J, Meske DS, Chung MK, et al. Injectable capsaicin for the management of pain due to osteoarthritis. Molecules. 2021;26(4):778.","journal-title":"Molecules"},{"key":"1272_CR76","unstructured":"Connolly J, Campbell J, Stevens R, Newman C, editors. Combined datasets for CNTX-4975 Osteoarthritis Knee Pain (OAKP) phase 3 trials (OAKP 301 and 304) to assess overall efficacy and safety of an intra-articular injection (IAI) of CNTX-4975-05 (CNTX) in subjects with chronic, moderate-to-severe osteoarthritis knee pain (MSOAKP). ACR Convergence; 2023 10\u201315 Nov, 2023; San Diego (CA)."},{"key":"1272_CR77","doi-asserted-by":"publisher","DOI":"10.3390\/biom14030292","author":"C Chen","year":"2024","unstructured":"Chen C, Yang F, Chen R, Yang C, Xiao H, Geng B, et al. TRPV channels in osteoarthritis: a comprehensive review. Biomolecules. 2024\u00a0Feb 29;14(3):292.\u00a0https:\/\/doi.org\/10.3390\/biom14030292.","journal-title":"Biomolecules"},{"issue":"2","key":"1272_CR78","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1097\/ALN.0000000000005027","volume":"141","author":"SL Shafer","year":"2024","unstructured":"Shafer SL, Teichman SL, Gottlieb IJ, Singla N, Minkowitz HS, Leiman D, et al. Safety and efficacy of vocacapsaicin for management of postsurgical pain: a randomized clinical trial. Anesthesiology. 2024;141(2):250\u201361.","journal-title":"Anesthesiology"},{"key":"1272_CR79","doi-asserted-by":"crossref","unstructured":"Teichman S, Minkowitz H, Leiman D, Solanki D, Garza J, Solomon B, et al., editors. Pilot study of vocacapsaicin for treatment of pain following open laparotomy repair of ventral hernia. ASRA; 31 Mar\u20132 Apr, 2022; Las Vegas (NV).","DOI":"10.1097\/01.XCS.0000895796.73917.3d"},{"key":"1272_CR80","unstructured":"Teichman S, Shafer S, Vaughn B, Donovan J, editors. TRPV1 from bench to bedside: vocacapsaicin produces durable postsurgical analgesia and earlier opioid cessation. IASP; 5\u20139 Aug, 2024; Amsterdam."},{"key":"1272_CR81","unstructured":"ConcentricAnalgesics. Concentric Analgesics announces data highlighting two weeks of durable pain relief and earlier cessation of opioids in two surgical procedures 2024 [updated August 6]. https:\/\/www.concentricanalgesics.com\/announcing-data-highlighting-two-weeks-of-durable-pain-relief-and-earlier-cessation-of-opioids. Accessed 22 Jan 2026."},{"issue":"10","key":"1272_CR82","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1080\/14728222.2024.2416961","volume":"28","author":"A Mobasheri","year":"2024","unstructured":"Mobasheri A, Rannou F, Ivanavicius S, Conaghan PG. Targeting the TRPV1 pain pathway in osteoarthritis of the knee. Expert Opin Ther Targets. 2024;28(10):843\u201356.","journal-title":"Expert Opin Ther Targets"},{"issue":"6","key":"1272_CR83","doi-asserted-by":"publisher","DOI":"10.1097\/PR9.0000000000000696","volume":"3","author":"P Arsenault","year":"2018","unstructured":"Arsenault P, Chiche D, Brown W, Miller J, Treister R, Leff R, et al. NEO6860, modality-selective TRPV1 antagonist: a randomized, controlled, proof-of-concept trial in patients with osteoarthritis knee pain. PAIN Rep. 2018;3(6):e696.","journal-title":"PAIN Rep"},{"issue":"4","key":"1272_CR84","doi-asserted-by":"publisher","DOI":"10.1097\/PR9.0000000000000576","volume":"1","author":"P Manitpisitkul","year":"2016","unstructured":"Manitpisitkul P, Brandt M, Flores CM, Kenigs V, Moyer JA, Romano G, et al. TRPV1 antagonist JNJ-39439335 (mavatrep) demonstrates proof of pharmacology in healthy men: a first-in-human, double-blind, placebo-controlled, randomized, sequential group study. PAIN Rep. 2016;1(4):e576.","journal-title":"PAIN Rep"},{"issue":"7","key":"1272_CR85","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1002\/cpdd.413","volume":"7","author":"P Manitpisitkul","year":"2018","unstructured":"Manitpisitkul P, Shalayda K, Russell L, Sanga P, Solanki B, Caruso J, et al. Pharmacokinetics and safety of Mavatrep (JNJ-39439335), a TRPV1 antagonist in healthy Japanese and Caucasian men: a double-blind, randomized, placebo-controlled, sequential-group phase 1 study. Clin Pharmacol Drug Dev. 2018;7(7):712\u201326.","journal-title":"Clin Pharmacol Drug Dev"},{"key":"1272_CR86","unstructured":"MAC Clinical Research announces clinical development of Mavatrep, a TRPV1 antagonist analgesic drug [press release]. 15 May 2025."},{"key":"1272_CR87","unstructured":"AlzeCure. ACD440 2025. https:\/\/www.alzecurepharma.se\/en\/acd440\/. Accessed 22 Jan 2026."},{"issue":"10","key":"1272_CR88","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1002\/ejp.2299","volume":"28","author":"M Segerdahl","year":"2024","unstructured":"Segerdahl M, Rother M, Halldin MM, Popescu T, Schaffler K. Topically applied novel TRPV1 receptor antagonist, ACD440 gel, reduces evoked pain in healthy volunteers, a randomized, double-blind, placebo-controlled, crossover study. Eur J Pain. 2024;28(10):1656\u201373.","journal-title":"Eur J Pain"},{"key":"1272_CR89","doi-asserted-by":"publisher","DOI":"10.1515\/sjpain-2025-0011","author":"A Miclescu","year":"2025","unstructured":"Miclescu A, Karlsten R, Lonnstedt I, Halldin MM, Segerdahl M. Topically applied novel TRPV1 receptor antagonist, ACD440 Gel, reduces temperature-evoked pain in patients with peripheral neuropathic pain with sensory hypersensitivity, a randomized, double-blind, placebo-controlled, crossover study. Scand J Pain. 2025. https:\/\/doi.org\/10.1515\/sjpain-2025-0011.","journal-title":"Scand J Pain"},{"key":"1272_CR90","unstructured":"JMackem. R&D pipeline. from: https:\/\/jmackem.com\/en\/m22.php. Accessed 22 Jan 2026."},{"key":"1272_CR91","doi-asserted-by":"publisher","DOI":"10.3389\/fddsv.2023.1314077","volume":"3","author":"MWY Southey","year":"2023","unstructured":"Southey MWY, Brunavs M. Introduction to small molecule drug discovery and preclinical development. Front Drug Discov. 2023;3:131407.","journal-title":"Front Drug Discov"},{"key":"1272_CR92","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.2147\/DDDT.S128727","volume":"11","author":"J Lee","year":"2017","unstructured":"Lee J, Kim BH, Yu KS, Kim HS, Kim JD, Cho JY, et al. A first-in-human, double-blind, placebo-controlled, randomized, dose escalation study of DWP05195, a novel TRPV1 antagonist, in healthy volunteers. Drug Des Devel Ther. 2017;11:1301\u201313.","journal-title":"Drug Des Devel Ther."},{"key":"1272_CR93","unstructured":"Pila Pharma inks agreement with Lindus Health about next clinical trial with safety and obesity readouts [press release]. 24 Jul 2024."},{"key":"1272_CR94","unstructured":"Pila Pharma AB is granted Orphan Drug Designation status in the USA [press release]. 15 Jul 2022."}],"container-title":["CNS Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-026-01272-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40263-026-01272-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-026-01272-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T12:02:34Z","timestamp":1773489754000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40263-026-01272-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,21]]},"references-count":94,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["1272"],"URL":"https:\/\/doi.org\/10.1007\/s40263-026-01272-1","relation":{},"ISSN":["1172-7047","1179-1934"],"issn-type":[{"value":"1172-7047","type":"print"},{"value":"1179-1934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,21]]},"assertion":[{"value":"21 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Edward H. Tsai and Tong J. Gan have no conflicts of interest that are directly relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"EHT: writing (original draft), writing (review and editing), visualization, conceptualization. TJG: writing (original draft), writing (review and editing), visualization, conceptualization, supervision. Both authors have read and approved the final version of the article.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}}]}}