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Moreover, Pgp is known to confer multi\u2010drug resistance in cancer chemotherapy and brain diseases, such as epilepsy, and is highly regulated by inflammatory mediators. The involvement of inflammatory processes in neuropathological states has led us to investigate the effects of peripheral inflammatory hyperalgesia on transport properties at the BBB. In the present study, we examined the effects of \u03bb\u2010carrageenan\u2010induced inflammatory pain (CIP) on brain endothelium regulation of Pgp. Western blot analysis of enriched brain microvessel fractions showed increased Pgp expression 3\u2003h post\u2010CIP<jats:italic>. In situ<\/jats:italic> brain perfusion studies paralleled these findings with decreased brain uptake of the Pgp substrate and opiate analgesic, [<jats:sup>3<\/jats:sup>H] morphine. Cyclosporin A\u2010mediated inhibition of Pgp enhanced the uptake of morphine in \u03bb\u2010carrageenan and control animals. This indicates that the CIP induced decrease in morphine transport was the result of an increase in Pgp activity at the BBB. Furthermore, antinociception studies showed decreased morphine analgesia following CIP. The observation that CIP modulates Pgp at the BBB <jats:italic>in vivo<\/jats:italic> is critical to understanding BBB regulation during inflammatory disease states.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.04644.x","type":"journal-article","created":{"date-parts":[[2007,5,11]],"date-time":"2007-05-11T11:43:33Z","timestamp":1178883813000},"page":"1677-1690","source":"Crossref","is-referenced-by-count":87,"title":["Peripheral inflammatory hyperalgesia modulates morphine delivery to the brain: a role for P\u2010glycoprotein"],"prefix":"10.1111","volume":"102","author":[{"given":"Melissa J.","family":"Seelbach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Egleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,4,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"e_1_2_7_3_1","first-page":"191","article-title":"The engine of ABC proteins","volume":"18","author":"Altenberg G. 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