Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression

Abstract

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, lambda-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 lambda-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 lambda-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.