Nociceptive inhibition prevents inflammatory pain induced changes in the blood-brain barrier.
Previous studies by our group have shown that peripheral inflammatory insult, using the lambda-carrageenan inflammatory pain (CIP) model, induced alterations in the molecular and functional properties of the blood-brain barrier (BBB). The question remained whether these changes were mediated via an inflammatory and/or neuronal mechanism. In this study, we investigated the involvement of neuronal input from pain activity on alterations in BBB integrity by peripheral inhibition of nociceptive input. A perineural injection of 0.75% bupivacaine into the right hind leg prior to CIP was used for peripheral nerve block. Upon nerve block, there was a significant decrease in thermal allodynia induced by CIP, but no effect on edema formation 1 h post-CIP. BBB permeability was increased 1 h post-CIP treatment as determined by in situ brain perfusion of [(14)C] sucrose; bupivacaine nerve block of CIP caused an attenuation of [(14)C] sucrose permeability, back to saline control levels. Paralleling the changes in [(14)C] sucrose permeability, we also report increased expression of three tight junction (TJ) proteins, zonula occluden-1 (ZO-1), occludin and claudin-5 with CIP. Upon bupivacaine nerve block, changes in expression were prevented. These data show that the lambda-carrageenan-induced changes in [(14)C] sucrose permeability and protein expression of ZO-1, occludin and claudin-5 are prevented with inhibition of nociceptive input. Therefore, we suggest that nociceptive signaling is in part responsible for the alteration in BBB integrity under CIP.
Department of Medical Pharmacology, College of Medicine, The University of Arizona, 1501 N Campbell Avenue, Tucson, AZ 85745, USA.
Christopher R
CR
Campos
Scott M
SM
Ocheltree
Sharon
S
Hom
Richard D
RD
Egleton
Thomas P
TP
Davis
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology*; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology*; D002045:Bupivacaine / Q000494:pharmacology; D002351:Carrageenan / Q000037:antagonists & inhibitors; D062507:Claudin-5; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000150:complications / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D008565:Membrane Proteins / Q000378:metabolism; D009407:Nerve Block / Q000379:methods; D009619:Nociceptors / Q000187:drug effects*; D062793:Occludin; D010146:Pain / Q000150:complications / Q000503:physiopathology*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D013395:Sucrose / Q000493:pharmacokinetics; D019108:Tight Junctions / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D000779:Anesthetics, Local; D062507:Claudin-5; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D013395:Sucrose; D002351:Carrageenan; D002045:Bupivacaine