TRPV1 and Thermosensitivity

Overview

Journal J Physiol Sci

Specialty Physiology

Date 2025 Feb 11

PMID 39933439

Authors

Makoto Tominaga

Moe Iwata

Affiliations

Soon will be listed here.

Abstract

The capsaicin receptor TRPV1 was identified as the first heat-activated ion channel in 1997. Since then, numerous studies have been performed on its physiological functions and structure-function relationship, and chemicals targeting TRPV1 have been developed. It has been more than 27 years since the initial cloning of the TRPV1 gene and more than 11 years since the clarification of its structure at the atomic level using cryo-EM. However, we still lack good chemical antagonists of TRPV1 as medicines. TRPV1 is involved in body temperature regulation, but how TRPV1 antagonists cause hyperthermia and how TRPV1 is involved in body temperature regulation are not yet clearly understood. More research is needed in the thermal biology field.

References

Cao E, Liao M, Cheng Y, Julius D . TRPV1 structures in distinct conformations reveal activation mechanisms. Nature. 2013; 504(7478):113-8. PMC: 4023639. DOI: 10.1038/nature12823. View

Laursen W, Schneider E, Merriman D, Bagriantsev S, Gracheva E . Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels. Proc Natl Acad Sci U S A. 2016; 113(40):11342-11347. PMC: 5056056. DOI: 10.1073/pnas.1604269113. View

Vandewauw I, Clercq K, Mulier M, Held K, Pinto S, Van Ranst N . A TRP channel trio mediates acute noxious heat sensing. Nature. 2018; 555(7698):662-666. DOI: 10.1038/nature26137. View

Iida T, Shimizu I, Nealen M, Campbell A, Caterina M . Attenuated fever response in mice lacking TRPV1. Neurosci Lett. 2005; 378(1):28-33. DOI: 10.1016/j.neulet.2004.12.007. View

Tominaga M, Caterina M, Malmberg A, Rosen T, Gilbert H, Skinner K . The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998; 21(3):531-43. DOI: 10.1016/s0896-6273(00)80564-4. View

Brauchi S, Orta G, Salazar M, Rosenmann E, Latorre R . A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels. J Neurosci. 2006; 26(18):4835-40. PMC: 6674176. DOI: 10.1523/JNEUROSCI.5080-05.2006. View

Zhang K, Julius D, Cheng Y . Structural snapshots of TRPV1 reveal mechanism of polymodal functionality. Cell. 2021; 184(20):5138-5150.e12. PMC: 8488022. DOI: 10.1016/j.cell.2021.08.012. View

Quiding H, Jonzon B, Svensson O, Webster L, Reimfelt A, Karin A . TRPV1 antagonistic analgesic effect: a randomized study of AZD1386 in pain after third molar extraction. Pain. 2013; 154(6):808-12. DOI: 10.1016/j.pain.2013.02.004. View

Garami A, Steiner A, Pakai E, Wanner S, Almeida M, Keringer P . The neural pathway of the hyperthermic response to antagonists of the transient receptor potential vanilloid-1 channel. Temperature (Austin). 2023; 10(1):136-154. PMC: 10177699. DOI: 10.1080/23328940.2023.2171671. View

10.

Oh U, Hwang S, Kim D . Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons. J Neurosci. 1996; 16(5):1659-67. PMC: 6578684. View

11.

Ujisawa T, Sasajima S, Kashio M, Tominaga M . Thermal gradient ring reveals different temperature-dependent behaviors in mice lacking thermosensitive TRP channels. J Physiol Sci. 2022; 72(1):11. PMC: 10717490. DOI: 10.1186/s12576-022-00835-3. View

12.

Garami A, Pakai E, McDonald H, Reilly R, Gomtsyan A, Corrigan J . TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development. Acta Physiol (Oxf). 2018; 223(3):e13038. PMC: 6032921. DOI: 10.1111/apha.13038. View

13.

Gavva N, Treanor J, Garami A, Fang L, Surapaneni S, Akrami A . Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain. 2008; 136(1-2):202-10. DOI: 10.1016/j.pain.2008.01.024. View

14.

Manitpisitkul P, Brandt M, Flores C, Kenigs V, Moyer J, Romano G . 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. 2018; 1(4):e576. PMC: 5741288. DOI: 10.1097/PR9.0000000000000576. View

15.

Nguyen T, Chapman S, Kashio M, Saito C, Strom T, Yasui M . Single amino acids set apparent temperature thresholds for heat-evoked activation of mosquito transient receptor potential channel TRPA1. J Biol Chem. 2022; 298(9):102271. PMC: 9396403. DOI: 10.1016/j.jbc.2022.102271. View

16.

Vlachova V, Teisinger J, Susankova K, Lyfenko A, Ettrich R, Vyklicky L . Functional role of C-terminal cytoplasmic tail of rat vanilloid receptor 1. J Neurosci. 2003; 23(4):1340-50. PMC: 6742269. View

17.

Yue W, Yuan L, Braz J, Basbaum A, Julius D . TRPV1 drugs alter core body temperature via central projections of primary afferent sensory neurons. Elife. 2022; 11. PMC: 9377796. DOI: 10.7554/eLife.80139. View

18.

Katz B, Zaguri R, Edvardson S, Maayan C, Elpeleg O, Lev S . Nociception and pain in humans lacking a functional TRPV1 channel. J Clin Invest. 2022; 133(3). PMC: 9888381. DOI: 10.1172/JCI153558. View

19.

Gao Y, Cao E, Julius D, Cheng Y . TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature. 2016; 534(7607):347-51. PMC: 4911334. DOI: 10.1038/nature17964. View

20.

Huang Y, Ma J, Bian Y, Bai Q, Gao Y, Di S . TRPV1 analgesics disturb core body temperature via a biased allosteric mechanism involving conformations distinct from that for nociception. Neuron. 2024; 112(11):1815-1831.e4. DOI: 10.1016/j.neuron.2024.02.016. View