Roles of serotonergic and adrenergic receptors in the antinociception of selective cyclooxygenase-2 inhibitor in the rat spinal cord.
BACKGROUND
The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level.


METHODS
DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, α1 adrenergic and α2 adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed.


RESULTS
Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test.


CONCLUSIONS
Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.
Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Gwangju, Korea.
Hye Jin
HJ
Jeong
Seong Heon
SH
Lee
Soo Young
SY
Cho
Cha Sup
CS
Lee
Cheol Won
CW
Jeong
Myung Ha
MH
Yoon
Woong Mo
WM
Kim