Synergistic analgesic interactions between the periaqueductal gray and the locus coeruleus Journal Article
| Authors: | Bodnar, R.; Paul, D.; Pasternak, G. W. |
| Article Title: | Synergistic analgesic interactions between the periaqueductal gray and the locus coeruleus |
| Abstract: | Opiates modulate pain perception at a number of different levels within the central nervous system and the importance of synergistic spinal and supraspinal influences have been well documented. In the present study we demostrate synergistic interactions between the periaqueductal gray and locus coeruleus. Administered either systemically or intracerebroventricularly (i.c.v.), ethylketocyclazonine elicits a potent naloxonazine-sensitive analgesia, indicating a μ1 action. μ1 Receptors also play a major role in opioid analgesic mechanisms in the periaqueductal gray and the locus coeruleus. However, microinjection of EKC into either the periaqueductal gray or locus coeruleus failed to elicit an analgesic response at any dose tested (0.1-20 μg) and, in additional studies, antagonized the analgesic actions of coadministered morphine or [D-Ser2,Leu5]enkephalin-Thr6 (DSLET). However, the simultaneous administration of EKC into both the periaqueductal gray (10 μg) and the locus coeruleus (10 μg; total combined dose 20 μg) produced a potent naloxonazine-sensitive analgesia greater than that observed with 50 μg i.c.v. These results suggest that EKC is a partial μ1 agonist which lacks the efficacy to elicit analgesia when microinjected into either of the two brain regions alone. However, when exposed to several regions at once, either through simultaneous microinjections into the periaqueductal gray and locus coeruleus or by injection into the ventricle, EKC is a potent μ1 analgesic. These results point out the existence of synergistic supraspinal interactions between the periaqueductal gray and the locus coeruleus, similar to the spinal/supraspinal interactions observed previously. © 1991. |
| Keywords: | controlled study; nonhuman; animal; pain; opiate; animal experiment; locus ceruleus; rat; rats; morphine; analgesics; analgesia; mu opiate receptor; receptors, opioid, mu; tail flick test; microinjections; receptors, opioid, delta; stereotaxic techniques; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; enkephalin; ethylketazocine; kappa opiate receptor; naloxonazine; rats, inbred strains; periaqueductal gray matter; locus coeruleus; periaqueductal gray; subcutaneous drug administration; reticular formation; receptors, opioid; intracerebroventricular drug administration; male; priority journal; article; receptors, opioid, kappa; enkephalin derivative; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; κ receptor; enkephalin, leucine; μ1 receptor; leucine enkephalin[2 dextro serine 6 threonine]; ethylketocyclazocine; raphe nuclei |
| Journal Title: | Brain Research |
| Volume: | 558 |
| Issue: | 2 |
| ISSN: | 0006-8993 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 1991-09-06 |
| Start Page: | 224 |
| End Page: | 230 |
| Language: | English |
| DOI: | 10.1016/0006-8993(91)90772-n |
| PUBMED: | 1664270 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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