{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:33:52Z","timestamp":1773099232568,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":59,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Intrathecal administration of \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonists produces potent analgesia. This study addressed the subtype of spinal \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor responsible for the analgesic effects of i.t. dexmedetomidine and ST\u201091 in the formalin behavioural model and their effects on primary afferent substance P (SP) release and spinal Fos activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>The analgesic effects of i.t. dexmedetomidine and ST\u201091 (\u03b1<jats:sub>2<\/jats:sub> agonists) were tested on the formalin behavioural model. To determine the subtype of \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor involved in the analgesia, i.t. BRL44408 (\u03b1<jats:sub>2A<\/jats:sub> antagonist) or ARC239 (\u03b1<jats:sub>2B\/C<\/jats:sub> antagonist) were given before dexmedetomidine or ST\u201091. Moreover, the ability of dexmedetomidine and ST\u201091 to inhibit formalin\u2010induced release of SP from primary afferent terminals was measured by the internalization of neurokinin<jats:sub>1<\/jats:sub> (NK<jats:sub>1<\/jats:sub>) receptors. Finally, the effects of dexmedetomidine on formalin\u2010induced Fos expression were assessed in the dorsal horn.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Intrathecal administration of dexmedetomidine or ST\u201091 dose\u2010dependently reduced the formalin\u2010induced paw\u2010flinching behaviour in rats. BRL44408 dose\u2010dependently blocked, whereas ARC239 had no effect on the analgesic actions of dexmedetomidine and ST\u201091. Dexmedetomidine and ST\u201091 had no effect on the formalin\u2010induced NK<jats:sub>1<\/jats:sub> receptor internalization, while morphine significantly reduced the NK<jats:sub>1<\/jats:sub> receptor internalization. On the other hand, both dexmedetomidine and morphine diminished the formalin\u2010induced Fos activation. The effect of dexmedetomidine on formalin\u2010induced Fos activation was reversed by BRL44408, but not ARC239.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and implications:<\/jats:title><jats:p>These findings suggest that \u03b1<jats:sub>2A<\/jats:sub>\u2010adrenoceptors mediate dexmedetomidine and ST\u201091 analgesia. This effect could be through a mechanism postsynaptic to primary afferent terminals, distinct from that of morphine.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2008) <jats:bold>155<\/jats:bold>, 1117\u20131126; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.341\">10.1038\/bjp.2008.341<\/jats:ext-link>; published online 1 September 2008<\/jats:p><\/jats:sec>","DOI":"10.1038\/bjp.2008.341","type":"journal-article","created":{"date-parts":[[2008,8,25]],"date-time":"2008-08-25T10:37:44Z","timestamp":1219660664000},"page":"1117-1126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Dexmedetomidine and ST\u201091 analgesia in the formalin model is mediated by \u03b1<sub>2A<\/sub>\u2010adrenoceptors: a mechanism of action distinct from 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