Supraspinal circuitry mediating opioid antinociception: antagonist and synergy studies in multiple sites.
Supraspinal opioid antinociception is mediated by sensitive brain sites capable of supporting this response following microinjection of opioid agonists. These sites include the ventrolateral periaqueductal gray (vIPAG), the rostral ventromedial medulla (RVM), the locus coeruleus and the amygdala. Each of these sites comprise an interconnected anatomical and physiologically relevant system mediating antinociceptive responses through regional interactions. Such interactions have been identified using two pharmacological approaches: (1) the ability of selective antagonists delivered to one site to block antinociception elicited by opioid agonists in a second site, and (2) the presence of synergistic antinociceptive interactions following simultaneous administration of subthreshold doses of opioid agonists into pairs of sites. Thus, the RVM has essential serotonergic, opioid, cholinergic and NMDA synapses that are necessary for the full expression of morphine antinociception elicited from the vIPAG, and the vIPAG has essential opioid synapses that are necessary for the full expression of opioid antinociception elicited from the amygdala. Further, the vIPAG, RVM, locus coeruleus and amygdala interact with each other in synergistically supporting opioid antinociception.
Bodnar
R J
RJ
Department of Psychology and Neuropsychology Doctoral Subprogram, Queens College, City University of New York, Flushing, NY 11367, USA. richard_bodnar@qc.edu
D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism* / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects*; D006801:Humans; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009294:Narcotics