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Department of Pharmacology, University of Arizona College of Medicine, Tucson, Arizona 85724
Effects of inflammatory pain
states on functional and molecular properties of the rat blood-brain
barrier (BBB) were investigated. Inflammation was produced by
subcutaneous injection of formalin, 
-carrageenan, or complete
Freund's adjuvant (CFA) into the right hind paw. In situ perfusion and
Western blot analyses were performed to assess BBB integrity after
inflammatory insult. In situ brain perfusion determined that peripheral
inflammation significantly increased the uptake of sucrose into the
cerebral hemispheres. Capillary depletion and cerebral blood flow
analyses indicated the perturbations were due to increased paracellular
permeability rather than vascular volume changes. Western blot analyses
showed altered tight junctional protein expression during peripheral inflammation. Occludin significantly decreased in the -carrageenan- and CFA-treated groups. Zonula occluden-1 expression was significantly increased in all pain models. Claudin-1 protein expression was present
at the BBB and remained unchanged during inflammation. Actin expression
was significantly increased in the -carrageenan- and CFA-treated
groups. We have shown that inflammatory-mediated pain alters both the
functional and molecular properties of the BBB. Inflammatory-induced
changes may significantly alter delivery of therapeutic agents to the
brain, thus affecting dosing regimens during chronic pain.
tight junctional proteins; microvascular endothelium; in situ perfusion; Western blot; cerebral blood flow
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