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-carrageenan-induced inflammatory pain
Department of Pharmacology, University of Arizona College of Medicine, Tucson, Arizona 85724
In this study, we examined
the effect of 
-carrageenan-induced inflammatory pain on the
functional and structural properties of the rat blood-brain barrier
(BBB) over a 72-h time period. Systemic inflammation was induced by an
intraplantar injection of 3% -carrageenan into the right hind paw
of female Sprague-Dawley rats. In situ brain perfusion and Western blot
analyses were performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ
brain perfusion showed -carrageenan significantly increased brain
uptake of [14C]sucrose at 1, 3, 6, and 48 h
(139 ± 9%, 166 ± 19%, 138 ± 13%, and 146 ± 7% compared with control, respectively). Capillary depletion analysis
insured the increased brain uptake was due to increased BBB
permeability and not vascular trapping. Western blot analyses for
zonula occludens-1 (ZO-1) and occludin were performed on isolated cerebral microvessels. ZO-1 expression was significantly increased at
1, 3, and 6 h and returned to control expression levels by 12 h. Total occludin expression was significantly reduced at 1, 3, 6, 12, and 48 h. This investigation demonstrated that
-carrageenan-induced inflammatory pain elicits a biphasic increase
in BBB permeability with the first phase occurring from 1-6 h and
the second phase occuring at 48 h. Furthermore, changes in BBB
function are correlated with altered tight junctional protein
expression of occludin and ZO-1. Changes in the structure of tight
junctions may have important clinical ramifications concerning central
nervous system homeostasis and therapeutic drug delivery.
inflammation; ZO-1; ZO-2; membrane-associated guanylate kinase; occludin; immunoprecipitation
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