PT  - JOURNAL ARTICLE
AU  - Tracy A. Brooks
AU  - Nicole Nametz
AU  - Rachael Charles
AU  - Thomas P. Davis
TI  - Diclofenac Attenuates the Regional Effect of λ-Carrageenan on Blood-Brain Barrier Function and Cytoarchitecture
AID  - 10.1124/jpet.107.135632
DP  - 2008 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 665--673
VI  - 325
IP  - 2
4099  - http://jpet.aspetjournals.org/content/325/2/665.short
4100  - http://jpet.aspetjournals.org/content/325/2/665.full
SO  - J Pharmacol Exp Ther2008 May 01; 325
AB  - The microenvironment of the brain requires tight regulation for proper neuronal function. Protecting the central nervous system (CNS) from the varying concentrations of ions, proteins, and toxins in the periphery is the dynamically regulated blood-brain barrier (BBB). Recent studies have demonstrated significant modulation of the BBB in a number of diseases and physiological states, including pain. This study expands on previous explorations of acute and chronic pain-induced effects on the function and molecular cytoarchitecture of the barrier. It describes the role of cyclooxygenase (COX) up-regulation by blocking with diclofenac (30 mg/kg, i.p.), and it examines the variation in BBB regulation through various brain regions. Edema and hyperalgesia were induced by λ-carrageenan and attenuated by the additional administration of diclofenac. Examination of unidirectional [14C]sucrose permeability with multitime in situ perfusion studies demonstrated that λ-carrageenan significantly increased cerebral permeability and decreased brainstem permeability. There were no significant changes in any of the other brain regions examined. These permeability changes correlated with up- and down-regulation of the tight junction (TJ) protein claudin-5 in the cerebrum and brainstem, respectively. Diclofenac administration attenuated the cerebral permeability uptake as well as the claudin-5 up-regulation. In addition, diclofenac reversed the lowered permeability in the brainstem, but it did not attenuate TJ protein expression. These studies demonstrate the complex regulation of the BBB occurring during inflammatory pain and the role of COX in this process. An understanding of BBB regulation during pain states is critically important for pharmacotherapy, and it holds great promise for new therapies to treat central nervous system pathologies. The American Society for Pharmacology and Experimental Therapeutics