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

Effects of inflammatory pain states on functional and molecular properties of the rat blood-brain barrier (BBB) were investigated. Inflammation was pr oduced by subcutaneous injection of formalin, lambda -carrageenan, or compl ete Freund's adjuvant (CFA) into the right hind paw. In situ perfusion and Western blot analyses were performed to assess BBB integrity after inflamma tory insult. In situ brain perfusion determined that peripheral inflammatio n significantly increased the uptake of sucrose into the cerebral hemispher es. Capillary depletion and cerebral blood flow analyses indicated the pert urbations were due to increased paracellular permeability rather than vascu lar volume changes. Western blot analyses showed altered tight junctional p rotein expression during peripheral inflammation. Occludin significantly de creased in the lambda -carrageenan- and CFA-treated groups. Zonula occluden -1 expression was significantly increased in all pain models. Claudin-1 pro tein expression was present at the BBB and remained unchanged during inflam mation. Actin expression was significantly increased in the lambda -carrage enan- and CFA-treated groups. We have shown that inflammatory-mediated pain alters both the functional and molecular properties of the BBB. Inflammato ry-induced changes may significantly alter delivery of therapeutic agents t o the brain, thus affecting dosing regimens during chronic pain.