The effect of a peripheral block on inflammation-induced prostaglandin E2 and cyclooxygenase expression in rats.
BACKGROUND
Peripheral inflammatory pain is associated with an upregulation of spinal cord COX-2 (cyclooxygenase-2), with a subsequent increase in central prostaglandin E2 (PGE2) levels associated with the development of hyperalgesia. In this study, we evaluated the effect of bupivacaine administered via a nerve block or via a systemic route on the spinal expression of PGE2 and COX in a model of peripheral inflammation in rats.


METHODS
All rats randomly received three injections: 1) a left subcutaneous hindpaw injection (0.2 mL with either carrageenan 2% w/v or saline), 2) a left sciatic block (0.2 mL with either bupivacaine 0.5% or saline), and 3) a systemic injection (subcutaneous interscapular with 0.2 mL with either bupivacaine 0.5% or saline). Local edema, thermal, and mechanical hyperalgesia as well as cerebrospinal fluid PGE2 concentration and COX-1 and COX-2 expression in the spinal cord in dorsal root ganglions were measured.


RESULTS
We confirmed that a bupivacaine block attenuates hyperalgesia and local inflammation in a model of inflammatory pain. This effect was associated with an inhibition of the increase in COX-2 expression induced by peripheral inflammation in dorsal root ganglions and cord. The subsequent production of PGE2 in cerebrospinal fluid was also impaired. Systemic bupivacaine did not modify either the hyperalgesia and local inflammation or COX expression.


CONCLUSIONS
These results constitute a key element strongly suggesting that local anesthetics act at a different level when administered systematically or via a nerve block.
Beloeil
Hélène
H
Univ Paris-Sud, Faculté de Médecine, Laboratoire d'Anesthésie, UPRES EA 3540, F-94276 Le Kremlin Bicêtre, France. helene.beloeil@bct.aphp.fr
Gentili
Marc
M
Benhamou
Dan
D
Mazoit
Jean-Xavier
JX
D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000096:biosynthesis*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D004487:Edema / Q000188:drug therapy; D005786:Gene Expression Regulation / Q000187:drug effects*; D006930:Hyperalgesia; D007249:Inflammation; D008297:Male; D009407:Nerve Block / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D002045:Bupivacaine