Abstract
An antianalgesic action of intracerebroventricularly administered nociceptin was elicited against intrathecal morphine-induced antinociception in the tail-flick test in mice and investigated as a descending neuronal system for the spinal mediator involved. The nociceptin-induced antianalgesia originating in the brain was inhibited by intrathecally administered indomethacin and suggested the mediation of spinal prostaglandin. The antianalgesic action of intracerebroventricular nociceptin was closely matched by intrathecal prostaglandin (PG) E2. Both shifted the dose-response curve of morphine to the right and these actions were eliminated by intrathecal PGD2. Desensitization of the antianalgesic action of PGE2 by intrathecal PGE2 pretreatment also produced cross-desensitization to the antianalgesic action of intracerebroventricular nociceptin. Neither intracerebroventricular nociceptin nor intrathecal PGE2 produced antianalgesia against the δ-receptor agonists given intrathecally. Thus, the antianalgesic action of nociceptin originating in the brain is coupled to a descending neuronal pathway mediated by spinal PGE2.
Footnotes
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Send reprint requests to: Jodie J. Rady, Research Service-151, VA Medical Center, Milwaukee, WI 53295. E-mail:jrady{at}mcw.edu
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This study was supported by Veterans Affairs Medical Funds (VA Merit Review, Research Career Scientist Award, to J.M.F.) and U.S. Public Health Service Grant RO1DA09155 (to W.B.C.).
- Abbreviations:
- i.t.
- intrathecal(ly)
- PG
- prostaglandin
- % MPE
- percentage of maximum possible effect
- DPDPE
- [d-Pen2,5]-enkephalin
- DSLET
- [d-Ser2,Leu5]-enkephalin-Thr
- EP
- prostanoid E
- SP
- substance P
- i.c.v.
- intracerebroventricular(ly)
- Received June 22, 2000.
- Accepted September 1, 2000.
- U.S. Government
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