{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T18:11:41Z","timestamp":1782843101112,"version":"3.54.5"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004686","name":"Deanship of Scientific Research, King Faisal University","doi-asserted-by":"publisher","award":["4546"],"award-info":[{"award-number":["4546"]}],"id":[{"id":"10.13039\/501100004686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transient receptor potential vanilloid type\u20101 (TRPV1) channels play key roles in chronic pain conditions and are modulated by different inflammatory mediators to elicit heat sensitisation. Bradykinin is a 9\u2010amino acid peptide chain that promotes inflammation. The aim of present study is to investigate how bradykinin and prostaglandin receptors (EP<jats:sub>3<\/jats:sub> and EP<jats:sub>4<\/jats:sub>) modulate the sensitisation of TRPV1\u2010mediated responses. Calcium imaging studies of rat dorsal root ganglion (DRG) neurons were employed to investigate the desensitizing responses of TRPV1 ion channels by capsaicin, and the re\u2010sensitization of TRPV1 by bradykinin, then to explore the role EP<jats:sub>3<\/jats:sub> and EP<jats:sub>4<\/jats:sub> receptors in mediating these bradykinin\u2010dependent effects. Immunocytochemistry was used to study the co\u2010expression and distribution of EP4, TRPV1, COX\u20101 and B2 in rat DRG neurons. Desensitization was seen upon repeated capsaicin application, we show that bradykinin\u2010mediated sensitization of capsaicin\u2010evoked calcium responses in rat DRG neurons occurs is dependent on COX\u20101 activity and utilizes a pathway that involves EP<jats:sub>4<\/jats:sub> but not EP<jats:sub>3<\/jats:sub> receptors. Immunocytochemical techniques revealed that EP4, TRPV1, COX\u20101 and B2 proteins are expressed mainly in small diameter (&lt;1000\u2009\u03bcm<jats:sup>2<\/jats:sup>) cell bodies of rat DRG neurons which are typically nociceptors. The present study provides suggestive evidence for a potential signalling pathway through which bradykinin may regulate TRPV1 ion channel function via EP4 receptors. In addition to confirming existing knowledge, the anatomical distribution and colocalization of these proteins in DRG neurons as revealed by this study offer valuable insight.<\/jats:p>","DOI":"10.1111\/bcpt.13967","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T23:24:25Z","timestamp":1701127465000},"page":"345-360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Role of bradykinin and prostaglandin EP4 receptors in regulating TRPV1 channel sensitization in rat dorsal root ganglion neurons"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6708-9706","authenticated-orcid":false,"given":"Sara A.","family":"Aldossary","sequence":"first","affiliation":[{"name":"Faculty of Clinical Pharmacy King Faisal University  Hofuf Saudi 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