
<ArticleTitle><prot><prot>p38</prot> stress-activated protein kinase</prot> inhibitor reverses <prot><prot>bradykinin B(1)</prot> receptor</prot>-mediated component of inflammatory hyperalgesia.</ArticleTitle>
<AbstractText>The effects of a <prot><prot>p38</prot> stress-activated protein kinase</prot> inhibitor, 4-(4-fluorophenyl)-2-(-4-methylsulfonylphenyl)-5-(4-pyridynyl) imidazole (SB203580), were evaluated in a rat model of inflammatory hyperalgesia. Oral, but not intrathecal, administration of SB203580 significantly reversed inflammatory mechanical hyperalgesia induced by injection of complete Freund's adjuvant into the hindpaw. SB203580 did not, however, affect the increased levels of <prot>interleukin-1beta</prot> and <prot>cyclo-oxygenase 2 protein</prot> observed in the hindpaw following complete Freund's adjuvant injection. Intraplantar injection of <prot>interleukin-1beta</prot> into the hindpaw elicited mechanical hyperalgesia in the ipsilateral paw, as well as in the contralateral paw, following intraplantar injection of the <prot><prot>bradykinin B(1)</prot> receptor</prot> agonist <prot>des-Arg(9)-bradykinin</prot>. Oral administration of SB203580 1 h prior to <prot>interleukin-1beta</prot> administration prevented the development of hyperalgesia in the ipslateral paw and the contralateral <prot><prot>bradykinin B(1)</prot> receptor</prot>-mediated hyperalgesia. In addition, following <prot>interleukin-1beta</prot> injection into the ipsilateral paw, co-administration of SB203580 with <prot>des-Arg(9)-bradykinin</prot> into the contralateral paw inhibited the <prot><prot>bradykinin B(1)</prot> receptor</prot>-mediated hyperalgesia.In human embryonic kidney 293 cells expressing the human <prot><prot>bradykinin B(1)</prot> receptor</prot>, its agonist <prot>des-Arg(10)-kallidin</prot> produced a rapid phosphorylation of endogenous <prot><prot>p38</prot> stress-activated protein kinase</prot>. Our data suggest that <prot><prot>p38</prot> stress-activated protein kinase</prot> is involved in the development of inflammatory hyperalgesia in the rat, and that its pro-inflammatory effects involve the induction of the <prot><prot>bradykinin B(1)</prot> receptor</prot> as well as functioning as its downstream effector.</AbstractText>
