TRPV1 Receptor Modulators: Emerging Therapies for Neuropathic, Osteoarthritic, and Perioperative Pain

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):816–24.

Article  CAS  PubMed  Google Scholar 

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.

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):531–43.

Article  CAS  PubMed  Google Scholar 

Atawala NAV, Kalava A. TRPV1 modulation: a “spicy” approach to pain relief. ASRA Pain Medicine News. 2023;48.

Tominaga M, Tominaga T. Structure and function of TRPV1. Pflugers Arch. 2005;451(1):143–50.

Article  CAS  PubMed  Google Scholar 

Julius D. TRP channels and pain. Annu Rev Cell Dev Biol. 2013;29:355–84.

Article  CAS  PubMed  Google Scholar 

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):307–20.

Article  PubMed  Google Scholar 

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):153–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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):1681–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Google Scholar 

Szallasi A, Blumberg PM. Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev. 1999;51(2):159–212.

Article  CAS  PubMed  Google Scholar 

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(1–2):162–8.

Article  CAS  PubMed  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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. 3–22.

Google Scholar 

Yuan L, Chandel NS, Julius D. Mitochondrial activity tunes nociceptor resilience to excitotoxicity. Cell. 2025;188(23):6436-52.e18.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chung MK, Campbell JN. Use of capsaicin to treat pain: mechanistic and therapeutic considerations. Pharmaceuticals (Basel). 2016;9(4):66.

Article  PubMed  PubMed Central  Google Scholar 

Szallasi A. Vanilloid-sensitive neurons: a fundamental subdivision of the peripheral nervous system. J Peripher Nerv Syst. 1996;1(1):6–18.

CAS  PubMed  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

Brito R, Sheth S, Mukherjea D, Rybak LP, Ramkumar V. TRPV1: a potential drug target for treating various diseases. Cells. 2014;3(2):517–45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Szallasi A, Sheta M. Targeting TRPV1 for pain relief: limits, losers and laurels. Expert Opin Investig Drugs. 2012;21(9):1351–69.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

Iftinca M, Defaye M, Altier C. TRPV1-targeted drugs in development for human pain conditions. Drugs. 2021;81(1):7–27.

Article  CAS  PubMed  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

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.

PubMed  PubMed Central  Google Scholar 

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. 163–83.

Derry S, Moore RA. Topical capsaicin (low concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2012;2012(9):CD010111.

PubMed  PubMed Central  Google Scholar 

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):31–43.

Article  CAS  PubMed  Google Scholar 

Bragg S, Marrison ST, Haley S. Diabetic peripheral neuropathy: prevention and treatment. Am Fam Physician. 2024;109(3):226–32.

PubMed  Google Scholar 

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):1578–89.

Article  CAS  Google Scholar 

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):220–33.

Article  PubMed  PubMed Central  Google Scholar 

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.

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.

Comments (0)

No login
gif