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

J. D. Huber, K. A. Witt, S. Hom, R. D. Egleton, K. S. Mark, Thomas P Davis

Research output: Contribution to journalArticle

200 Citations (Scopus)

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, λ-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 λ-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 λ-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number3 49-3
StatePublished - 2001

Fingerprint

Blood-Brain Barrier
Freund's Adjuvant
Carrageenan
Permeability
Inflammation
Pain
Cerebrovascular Circulation
Proteins
Perfusion
Western Blotting
Claudins
Claudin-1
Occludin
Tight Junctions
Brain
Cerebrum
Capillary Permeability
Subcutaneous Injections
Chronic Pain
Formaldehyde

Keywords

  • Cerebral blood flow
  • In situ perfusion
  • Microvascular endothelium
  • Tight junctional proteins
  • Western blot

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Inflammatory pain alters blood-brain barrier permeability and tight junctional protein expression. / Huber, J. D.; Witt, K. A.; Hom, S.; Egleton, R. D.; Mark, K. S.; Davis, Thomas P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 280, No. 3 49-3, 2001.

Research output: Contribution to journalArticle

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