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
lambda-carrageenan and attenuated by the additional administration of
diclofenac. Examination of unidirectional [14C]
sucrose permeability with multitime in situ perfusion studies demonstrated that
lambda-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.