Faculty Collaboration Database

Supraspinal and spinal delta(2) opioid receptor-mediated antinociceptive synergy is mediated by spinal alpha(2) adrenoceptors. Pain 1999 Oct;83(1):47-55

Date

10/03/1999

Pubmed ID

10506671

DOI

10.1016/s0304-3959(99)00084-6

Scopus ID

2-s2.0-0032847514 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

Concurrent administration of low doses of [D-Ala(2), Glu(4)]deltorphin (DELT) in the spinal cord and rostral ventromedial medulla of the rat produces a synergistic antinociception in the tail-flick test. It was postulated that the synergistic antinociception results from an interaction of the intrathecally-administered DELT with norepinephrine released in the spinal cord as a result of the microinjection of DELT in the rostral ventromedial medulla. Three approaches were taken to test this hypothesis. The first experiment determined that microinjection of DELT in the rostral ventromedial medulla produced an increase in tail-flick latency that was partially attenuated by intrathecal administration of the alpha(2)-adrenoceptor antagonist yohimbine. These data indicated that microinjection of DELT in the medulla causes a release of norepinephrine in the spinal cord. The second experiment determined that intrathecal co-administration of DELT with the alpha(2)-adrenoceptor agonist dexmedetomidine in a 2:1 fixed dose ratio produced a synergistic antinociception in the tail-flick test. The final experiment determined that the antinociception produced by concurrent medullary and intrathecal administration of DELT was completely antagonized by intrathecal administration of yohimbine. Taken together, these findings support the hypothesis that the synergistic antinociception produced by concurrent activation of medullary and spinal delta(2) opioid receptors is mediated, in part, by endogenous norepinephrine release in the spinal cord. The norepinephrine, acting at alpha(2)-adrenoceptors, interacts in a synergistic manner with intrathecally administered DELT, acting at spinal delta(2) opioid receptors, to produce antinociception.

Author List

Grabow TS, Hurley RW, Banfor PN, Hammond DL

Author

Robert W. Hurley MD, PhD Adjunct Professor of Anesthesiology and CTSI in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic alpha-Agonists
Adrenergic alpha-Antagonists
Analgesics, Opioid
Anesthesia, Spinal
Animals
Dexmedetomidine
Drug Synergism
Injections, Spinal
Male
Nociceptors
Norepinephrine
Oligopeptides
Pain Measurement
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, alpha-2
Receptors, Opioid, delta
Spinal Cord
Yohimbine