{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:13:32Z","timestamp":1785248012118,"version":"3.55.0"},"reference-count":335,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The heat and capsaicin receptor TRPV1 channel is widely expressed in nerve terminals of dorsal root ganglia (DRGs) and trigeminal ganglia innervating the body and face, respectively, as well as in other tissues and organs including central nervous system. The TRPV1 channel is a versatile receptor that detects harmful heat, pain, and various internal and external ligands. Hence, it operates as a polymodal sensory channel. Many pathological conditions including neuroinflammation, cancer, psychiatric disorders, and pathological pain, are linked to the abnormal functioning of the TRPV1 in peripheral tissues. Intense biomedical research is underway to discover compounds that can modulate the channel and provide pain relief. The molecular mechanisms underlying temperature sensing remain largely unknown, although they are closely linked to pain transduction. Prolonged exposure to capsaicin generates analgesia, hence numerous capsaicin analogs have been developed to discover efficient analgesics for pain relief. The emergence of <jats:italic>in silico<\/jats:italic> tools offered significant techniques for molecular modeling and machine learning algorithms to indentify druggable sites in the channel and for repositioning of current drugs aimed at TRPV1. Here we recapitulate the physiological and pathophysiological functions of the TRPV1 channel, including structural models obtained through cryo-EM, pharmacological compounds tested on TRPV1, and the <jats:italic>in silico<\/jats:italic> tools for drug discovery and repositioning.<\/jats:p>","DOI":"10.3389\/fphar.2023.1251061","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T04:19:40Z","timestamp":1706069980000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["A journey from molecule to physiology and in silico tools for drug discovery targeting the transient receptor potential vanilloid type 1 (TRPV1) channel"],"prefix":"10.3389","volume":"14","author":[{"given":"Cesar A.","family":"Amaya-Rodriguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Carvajal-Zamorano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bustos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Alegr\u00eda-Arcos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/J.PUPT.2008.12.014","article-title":"TRPV1 receptors in sensitisation of cough and pain reflexes","volume":"22","author":"Adcock","year":"2009","journal-title":"Pulm. 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