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.
Campos
Christopher R
CR
Department of Medical Pharmacology, College of Medicine, The University of Arizona, 1501 N Campbell Avenue, Tucson, AZ 85745, USA.
Ocheltree
Scott M
SM
Hom
Sharon
S
Egleton
Richard D
RD
Davis
Thomas P
TP
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