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Volume 4,Issue 7

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20 June 2026

TRPV1、TRPA1 及TRPM8 在疼痛中的作用机制及研究进展

洁红 莫1 雷 赵2
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1 暨南大学第二临床医学院,深圳市人民医院麻醉科, 中国
2 暨南大学第二临床医学院,深圳市人民医院日间医疗中心, 中国
MRP 2026 , 4(6), 70–73; https://doi.org/10.61369/MRP.2026060025
© 2026 by the Author(s). Licensee Art and Technology, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

瞬时受体电位(TRP)通道是参与健康及疼痛、炎症、代谢紊乱等疾病过程的多功能信号分子。其中,TRPA1 和TRPM8 感知冷觉温度,而 TRPV1 感知热觉温度,三者均对温度伤害感受及神经病理性疼痛至关重要。阿片类镇痛药疗效有限,且会导致严重的依赖性和成瘾性。因此,研究 TRP 通道可为开发新型非成瘾性镇痛靶点提供新思路。本综述总结了与疼痛相关的关键 TRP 通道(TRPV1、TRPA1、TRPM8)的研究现状、致痛机制及抑制剂研究进展,阐述了其生物学特性及在不同疼痛类型中的作用,并对其作为非成瘾性镇痛靶点的临床转化前景进行了展望。

Keywords
TRP 离子通道
疼痛
镇痛分子靶点
References

[1]ZHANG M, MA Y, YE X, et al. TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases[J/OL].Signal Transduction and Targeted Therapy, 2023, 8(1): 261. DOI:10.1038/s41392-023-01464-x.
[2]VOLKOW N D, MCLELLAN A T. Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies[J/OL]. The New England Journal of Medicine, 2016, 374(13):1253-1263. DOI:10.1056/NEJMra1507771.
[3]WOOLF C J, MA Q. Nociceptors--noxious stimulus detectors[J/OL]. Neuron, 2007, 55(3): 353-364. DOI:10.1016/j.neuron.2007.07.016.
[4]CATERINA M J, SCHUMACHER M A, TOMINAGA M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway[J/OL]. Nature, 1997, 389(6653):816-824. DOI:10.1038/39807.
[5]MCKEMY D D, NEUHAUSSER W M, JULIUS D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation[J/OL]. Nature, 2002,416(6876): 52-58. DOI:10.1038/nature719.
[6]PEIER A M, MOQRICH A, HERGARDEN A C,et al. A TRP Channel that Senses Cold Stimuli and Menthol[J/OL]. Cell, 2002, 108(5): 705-715. DOI:10.1016/S0092-8674(02)00652-9.
[7]STORY G M, PEIER A M, REEVE A J, et al. ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures[J/OL]. Cell, 2003,112(6): 819-829. DOI:10.1016/S0092-8674(03)00158-2.
[8]MACPHERSON L J, DUBIN A E, EVANS M J, et al. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines[J/OL]. Nature, 2007, 445(7127): 541-545. DOI:10.1038/nature05544.
[9]YUE L, XU H. TRP channels in health and disease at a glance[J/OL]. Journal of Cell Science, 2021, 134(13): jcs258372. DOI:10.1242/jcs.258372.
[10]HUANG Y, FLIEGERT R, GUSE A H, et al. A structural overview of the ion channels of the TRPM family[J/OL]. Cell Calcium, 2020, 85: 102111. DOI:10.1016/j.ceca.2019.102111.
[11]JI R R, SAMAD T A, JIN S X, et al. p38 MAPK Activation by NGF in Primary Sensory Neurons after Inflammation Increases TRPV1 Levels and Maintains Heat Hyperalgesia[J/OL]. Neuron, 2002, 36(1): 57-68. DOI:10.1016/S0896-6273(02)00908-X.
[12]OBATA K. TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury[J/OL]. Journal of Clinical Investigation, 2005, 115(9): 2393-2401. DOI:10.1172/JCI25437.
[13]VOOLSTRA O, HUBER A. Post-Translational Modifications of TRP Channels[J/OL]. Cells, 2014, 3(2): 258-287. DOI:10.3390/cells3020258.
[14]ZHANG X, HUANG J, MCNAUGHTON P A. NGF rapidly increases membrane expression of TRPV1 heat‐gated ion channels[J/OL]. The EMBO Journal, 2005, 24(24): 4211-4223. DOI:10.1038/sj.emboj.7600893.
[15]Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons - PubMed汉化版[EB/OL]. [2026-03-31]. https://www.ipubmed.cn/Archive/Detail/8774434.
[16]CATERINA M J, SCHUMACHER M A, TOMINAGA M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway[J/OL]. Nature, 1997, 389(6653): 816-824. DOI:10.1038/39807.
[17]TOMINAGA M, CATERINA M J, MALMBERG A B, et al. The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli[J/OL]. Neuron, 1998, 21(3): 531-543. DOI:10.1016/S0896-6273(00)80564-4.
[18]JAHNEL R, DREGER M, GILLEN C, et al. Biochemical characterization of the vanilloid receptor 1 expressed in a dorsal root ganglia derived cell line[J/OL]. European Journal of Biochemistry, 2001, 268(21): 5489-5496. DOI:10.1046/j.1432-1033.2001.02500.x.
[19]WIRKNER K, HOGNESTAD H, JAHNEL R, et al. Characterization of rat transient receptor potential vanilloid 1 receptors lacking the N-glycosylation site N604:[J/OL]. NeuroReport, 2005, 16(9): 997-1001. DOI:10.1097/00001756-200506210-00023.
[20]CATERINA M J, LEFFLER A, MALMBERG A B, et al. Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor[J/OL]. Science, 2000, 288(5464): 306-313. DOI:10.1126/science.288.5464.306.
[21]DAVIS J B, GRAY J, GUNTHORPE M J, et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia[J/OL]. Nature, 2000, 405(6783): 183-187. DOI:10.1038/35012076.
[22]DAI Y. TRPs and pain[J/OL]. Seminars in Immunopathology, 2016, 38(3): 277-291. DOI:10.1007/s00281-015-0526-0.
[23]IZQUIERDO C, MARTÍN-MARTÍNEZ M, GÓMEZ-MONTERREY I, et al. TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation[J/OL]. International Journal of Molecular Sciences, 2021, 22(16): 8502. DOI:10.3390/ijms22168502.
[24]XING H, CHEN M, LING J, et al. TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury[J/OL]. The Journal of Neuroscience, 2007, 27(50): 13680-13690. DOI:10.1523/JNEUROSCI.2203-07.2007.
[25]PERTUSA M, SOLORZA J, MADRID R. Molecular determinants of TRPM8 function: key clues for a cool modulation[J/OL]. Frontiers in Pharmacology, 2023, 14: 1213337. DOI:10.3389/fphar.2023.1213337.
[26]LIU B, FAN L, BALAKRISHNA S, et al. TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain[J/OL]. Pain, 2013, 154(10): 2169-2177. DOI:10.1016/j.pain.2013.06.043.
[27]WINCHESTER W J, GORE K, GLATT S, et al. Inhibition of TRPM8 Channels Reduces Pain in the Cold Pressor Test in Humans[J/OL]. The Journal of Pharmacology and Experimental Therapeutics, 2014, 351(2): 259-269. DOI:10.1124/jpet.114.216010.
[28]CHUNG M K, CATERINA M J. TRP Channel Knockout Mice Lose Their Cool[J/OL]. Neuron, 2007, 54(3): 345-347. DOI:10.1016/j.neuron.2007.04.025.
[29]JAQUEMAR D, SCHENKER T, TRUEB B. An Ankyrin-like Protein with Transmembrane Domains Is Specifically Lost after Oncogenic Transformation of Human Fibroblasts[J/OL]. Journal of Biological Chemistry, 1999, 274(11): 7325-7333. DOI:10.1074/jbc.274.11.7325.
[30]STORY G M, PEIER A M, REEVE A J, et al. ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures[J/OL]. Cell, 2003, 112(6): 819-829. DOI:10.1016/S0092-8674(03)00158-2.
[31]VIANA F. TRPA1 channels: molecular sentinels of cellular stress and tissue damage[J/OL]. The Journal of Physiology, 2016, 594(15): 4151-4169. DOI:10.1113/JP270935.
[32]SAMAD A, SURA L, BENEDIKT J, et al. The C-terminal basic residues contribute to the chemical- and voltage-dependent activation of TRPA1[J/OL]. Biochemical Journal, 2011, 433(1): 197-204. DOI:10.1042/BJ20101256.
[33]GAUDET R. A primer on ankyrin repeat function in TRP channels and beyond[J/OL]. Molecular BioSystems, 2008, 4(5): 372-379. DOI:10.1039/B801481G.
[34]SUO Y, WANG Z, ZUBCEVIC L, et al. Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel[J/OL]. Neuron, 2020, 105(5): 882-894.e5. DOI:10.1016/j.neuron.2019.11.023.
[35]EBERHARDT M J, FILIPOVIC M R, LEFFLER A, et al. Methylglyoxal Activates Nociceptors through Transient Receptor Potential Channel A1 (TRPA1)[J/OL]. Journal of Biological Chemistry, 2012, 287(34): 28291-28306. DOI:10.1074/jbc.M111.328674.
[36]SUO Y, WANG Z, ZUBCEVIC L, et al. Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel[J/OL]. Neuron, 2020, 105(5): 882-894.e5. DOI:10.1016/j.neuron.2019.11.023.
[37]BESSAC B F, JORDT S E. Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control[J/OL]. Physiology, 2008, 23(6): 360-370. DOI:10.1152/physiol.00026.2008.
[38]SCHMIDT M, DUBIN A E, PETRUS M J, et al. Nociceptive Signals Induce Trafficking of TRPA1 to the Plasma Membrane[J/OL]. Neuron, 2009, 64(4): 498-509. DOI:10.1016/j.neuron.2009.09.030.
[39]ZYGMUNT P M, HÖGESTÄTT E D. TRPA1[M/OL]//NILIUS B, FLOCKERZI V. Mammalian Transient Receptor Potential (TRP) Cation Channels: 卷 222. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014: 583-630[2026-03-31]. https://link.springer.com/10.1007/978-3-642-54215-2_23. DOI:10.1007/978-3-642-54215-2_23.
[40]KOBAYASHI K, FUKUOKA T, OBATA K, et al. Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with aδ/c‐fibers and colocalization with trk receptors[J/OL]. Journal of Comparative Neurology, 2005, 493(4): 596-606. DOI:10.1002/cne.20794.
[41]FISCHER M J M, BALASURIYA D, JEGGLE P, et al. Direct evidence for functional TRPV1/TRPA1 heteromers[J/OL]. Pflügers Archiv - European Journal of Physiology, 2014, 466(12): 2229-2241. DOI:10.1007/s00424-014-1497-z.

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