{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:31:14Z","timestamp":1792704674126,"version":"4.5.0"},"reference-count":68,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,7,10]],"date-time":"2012-07-10T00:00:00Z","timestamp":1341878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic> (2012) <jats:bold>122<\/jats:bold>, 962\u2013975.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>P\u2010glycoprotein (ABCB1\/MDR1, EC 3.6.3.44), the major efflux transporter at the blood\u2013brain barrier (BBB), is a formidable obstacle to CNS pharmacotherapy. Understanding the mechanism(s) for increased P\u2010glycoprotein activity at the BBB during peripheral inflammatory pain is critical in the development of novel strategies to overcome the significant decreases in CNS analgesic drug delivery. In this study, we employed the \u03bb\u2010carrageenan pain model (using female Sprague\u2013Dawley rats), combined with confocal microscopy and subcellular fractionation of cerebral microvessels, to determine if increased P\u2010glycoprotein function, following the onset of peripheral inflammatory pain, is associated with a change in P\u2010glycoprotein trafficking which leads to pain\u2010induced effects on analgesic drug delivery. Injection of \u03bb\u2010carrageenan into the rat hind paw induced a localized, inflammatory pain (hyperalgesia) and simultaneously, at the BBB, a rapid change in colocalization of P\u2010glycoprotein with caveolin\u20101, a key scaffolding\/trafficking protein. Subcellular fractionation of isolated cerebral microvessels revealed that the bulk of P\u2010glycoprotein constitutively traffics to membrane domains containing high molecular weight, disulfide\u2010bonded P\u2010glycoprotein\u2010containing structures that cofractionate with membrane domains enriched with monomeric and high molecular weight, disulfide\u2010bonded, caveolin\u20101\u2010containing structures. Peripheral inflammatory pain promoted a dynamic redistribution between membrane domains of P\u2010glycoprotein and caveolin\u20101. Disassembly of high molecular weight P\u2010glycoprotein\u2010containing structures within microvascular endothelial luminal membrane domains was accompanied by an increase in ATPase activity, suggesting a potential for functionally active P\u2010glycoprotein. These results are the first observation that peripheral inflammatory pain leads to specific structural changes in P\u2010glycoprotein responsible for controlling analgesic drug delivery to the CNS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2012.07831.x","type":"journal-article","created":{"date-parts":[[2012,6,21]],"date-time":"2012-06-21T12:51:02Z","timestamp":1340283062000},"page":"962-975","source":"Crossref","is-referenced-by-count":69,"title":["P\u2010glycoprotein trafficking at the blood\u2013brain barrier altered by peripheral inflammatory hyperalgesia"],"prefix":"10.1111","volume":"122","author":[{"given":"Gwen","family":"McCaffrey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William 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