{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:48:32Z","timestamp":1791895712317,"version":"4.3.4"},"reference-count":141,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Caffeine (1,3,7-trimethylxanthine) is a naturally occurring methylxanthine that acts as a potent central nervous system stimulant found in more than 60 different plants and fruits. Although caffeinated beverages are widely and casually consumed, the application of caffeine beyond dietary levels as pharmacologic therapy has been recognized since the beginning of its recorded use. The analgesic and vasoactive properties of caffeine are well known, but the extent of their molecular basis remains an area of active research. There is existing evidence in the literature as to caffeine\u2019s effect on TRP channels, the role of caffeine in pain management and analgesia, as well as the role of TRP in pain and analgesia; however, there has yet to be a review focused on the interaction between caffeine and TRP channels. Although the influence of caffeine on TRP has been demonstrated in the lab and in animal models, there is a scarcity of data collected on a large scale as to the clinical utility of caffeine as a regulator of TRP. This review aims to prompt further molecular research to elucidate the specific ligand\u2013host interaction between caffeine and TRP by validating caffeine as a regulator of transient receptor potential (TRP) channels\u2014focusing on the transient receptor potential vanilloid 1 (TRPV1) receptor and transient receptor potential ankyrin 1 (TRPA1) receptor subtypes\u2014and its application in areas of pain.<\/jats:p>","DOI":"10.3390\/ijms25147903","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T09:14:53Z","timestamp":1721380493000},"page":"7903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["TRPA1, TRPV1, and Caffeine: Pain and Analgesia"],"prefix":"10.3390","volume":"25","author":[{"given":"Elizabeth A.","family":"Puthumana","sequence":"first","affiliation":[{"name":"Departments of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna","family":"Muhamad","sequence":"additional","affiliation":[{"name":"Departments of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lexi A.","family":"Young","sequence":"additional","affiliation":[{"name":"Departments of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6781-0468","authenticated-orcid":false,"given":"Xiang-Ping","family":"Chu","sequence":"additional","affiliation":[{"name":"Departments of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/0896-6273(89)90069-X","article-title":"Molecular characterization of the drosophila trp locus: A putative integral membrane protein required for phototransduction","volume":"2","author":"Montell","year":"1989","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev.biochem.75.103004.142819","article-title":"TRP channels","volume":"76","author":"Venkatachalam","year":"2007","journal-title":"Annu. 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