Supraspinal and spinal delta(2) opioid receptor-mediated antinociceptive synergy is mediated by spinal alpha(2) adrenoceptors

T S Grabow; R W Hurley; P N Banfor; D L Hammond

doi:10.1016/S0304-3959(99)00084-6

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Supraspinal and spinal delta(2) opioid receptor-mediated antinociceptive synergy is mediated by spinal alpha(2) adrenoceptors

Journal article

Peer reviewed

Supraspinal and spinal delta(2) opioid receptor-mediated antinociceptive synergy is mediated by spinal alpha(2) adrenoceptors

T S Grabow, R W Hurley, P N Banfor and D L Hammond

Pain (Amsterdam), Vol.83(1), pp.47-55

10/1999

DOI: 10.1016/S0304-3959(99)00084-6

PMID: 10506671

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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.

Norepinephrine - pharmacology

Spinal Cord - drug effects

Norepinephrine - physiology

Analgesics, Opioid - pharmacology

Nociceptors - physiology

Male

Adrenergic alpha-Antagonists - pharmacology

Anesthesia, Spinal

Yohimbine - pharmacology

Receptors, Adrenergic, alpha-2 - drug effects

Dexmedetomidine - pharmacology

Receptors, Adrenergic, alpha-2 - physiology

Injections, Spinal

Rats

Receptors, Opioid, delta - drug effects

Rats, Sprague-Dawley

Drug Synergism

Animals

Analgesics, Opioid - administration & dosage

Spinal Cord - physiology

Adrenergic alpha-Agonists - pharmacology

Oligopeptides - administration & dosage

Oligopeptides - pharmacology

Pain Measurement

Nociceptors - drug effects

Receptors, Opioid, delta - physiology

Details

Title: Subtitle: Supraspinal and spinal delta(2) opioid receptor-mediated antinociceptive synergy is mediated by spinal alpha(2) adrenoceptors
Creators: T S Grabow - Department of Anesthesiology and Critical Care, University of Chicago, 5841 South Maryland Avenue M/C 4028, Chicago, USA
R W Hurley
P N Banfor
D L Hammond
Resource Type: Journal article
Publication Details: Pain (Amsterdam), Vol.83(1), pp.47-55
Publisher: United States
DOI: 10.1016/S0304-3959(99)00084-6
PMID: 10506671
ISSN: 0304-3959
eISSN: 1872-6623
Grant note: F30DA05784 / NIDA NIH HHS R01DA06736 / NIDA NIH HHS
Language: English
Date published: 10/1999
Academic Unit: Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
Record Identifier: 9984006400602771

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