{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:33:05Z","timestamp":1792272785984,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2015,4,24]],"date-time":"2015-04-24T00:00:00Z","timestamp":1429833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Associazione Italiana per la Ricerca sul Cancro (AIRC)"},{"name":"Ente Cassa di Risparmio di Firenze-2010"},{"name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca,","award":["PRIN-2010Y4WMCR-007"],"award-info":[{"award-number":["PRIN-2010Y4WMCR-007"]}]},{"name":"Progetto Impatto-Ministero Dello Sviluppo Economico (2012-2013)"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Although still used by hundreds of millions of people worldwide, the mechanism of the analgesic action of the pyrazolone derivatives (\n PD<\/jats:styled-content>\n s), dipyrone, propyphenazone and antipyrine remains unknown. The transient receptor potential ankyrin 1 (\n TRPA<\/jats:styled-content>\n 1) channel, expressed by nociceptors, is emerging as a major pain transduction pathway. We hypothesized that\n PD<\/jats:styled-content>\n s target the\n TRPA<\/jats:styled-content>\n 1 channel and by this mechanism produce their analgesic effect.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Calcium responses and currents were studied in cultured\n TRPA<\/jats:styled-content>\n 1\u2010expressing rodent dorsal root ganglion neurons and human cells. Acute nociception and mechanical hypersensitivity were investigated in na\u00efve and genetically manipulated mice.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n Pyrazolone and\n PD<\/jats:styled-content>\n s selectively inhibited calcium responses and currents in\n TRPA<\/jats:styled-content>\n 1\u2010expressing cells and acute nocifensor responses in mice evoked by reactive channel agonists (allyl isothiocyanate, acrolein and\n \n H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n <\/jats:styled-content>\n ). In line with recent results obtained with\n TRPA<\/jats:styled-content>\n 1 antagonists and\n TRPA<\/jats:styled-content>\n 1 gene deletion, the two most largely used\n PD<\/jats:styled-content>\n s, dipyrone and propyphenazone, attenuated\n TRPA<\/jats:styled-content>\n 1\u2010mediated nociception and mechanical allodynia in models of inflammatory and neuropathic pain (formalin, carrageenan, partial sciatic nerve ligation and the chemotherapeutic drug, bortezomib). Notably, dipyrone and propyphenazone attenuated carrageenan\u2010evoked mechanical allodynia, without affecting\n PGE<\/jats:styled-content>\n 2<\/jats:sub>\n levels. The main metabolites of\n PDs<\/jats:styled-content>\n did not target\n TRPA<\/jats:styled-content>\n 1 and did not affect\n TRPA<\/jats:styled-content>\n 1\u2010dependent nociception and allodynia.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n Evidence that in rodents the nociceptive\/hyperalgesic effect produced by\n TRPA<\/jats:styled-content>\n 1 activation is blocked by\n PD<\/jats:styled-content>\n s suggests that a similar pathway is attenuated by\n PD<\/jats:styled-content>\n s in humans and that\n TRPA<\/jats:styled-content>\n 1 antagonists could be novel analgesics, devoid of the adverse haematological effects of\n PD<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.13129","type":"journal-article","created":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T05:18:28Z","timestamp":1426223908000},"page":"3397-3411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["The\n TRPA<\/scp>\n 1 channel mediates the analgesic action of dipyrone and pyrazolone derivatives"],"prefix":"10.1111","volume":"172","author":[{"given":"Romina","family":"Nassini","sequence":"first","affiliation":[{"name":"Department of Health Sciences Section of Clinical Pharmacology and Oncology University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Fusi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Section of Clinical Pharmacology and Oncology University of Florence Florence 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