MU-OPIOID AND DELTA-OPIOID RECEPTORS ARE EXPRESSED IN BRAIN-STEM ANTINOCICEPTIVE CIRCUITS - STUDIES USING IMMUNOCYTOCHEMISTRY AND RETROGRADE TRACT-TRACING

Opioid-produced antinociception in mammals seems to be mediated in par i by pathways originating in the periaqueductal gray (FAG) and the ros troventral medulla (RVM), and these pathways may include serotonergic neurons. In the present study, we examined the relationship of the clo ned mu- and delta-receptors (MOR1 and DOR1, respectively) to pAG neuro ns projecting to the RVM, and RVM neurons projecting to the dorsal spi nal cord. This was carried out by combining immunocytochemical stainin g for MOR1, DOR1, and serotonin with fluorescent retrograde tract-trac ing. Of 133 retrogradely labeled cells in the RVM, 31% were immunoreac tive for MOR1. Of the double-labeled cells, 41% also were immunoreacti ve for 5HT. Fifty-three percent of retrogradely labeled cells were app osed by DOR1-ir varicosities; 29% of the apposed cells were immunoreac tive for 5HT. In the mesencephalon, cells retrogradely labeled from th e RVM were usually surrounded by MORI-ir structures; however, retrogra dely labeled cells were never observed to be immunoreactive for MOR1. Similarly, retrogradely labeled cells in the caudal midbrain were seld om, if ever, labeled for DOR1; however, they frequently were apposed b y DOR1-ir varicosities. Of 156 retrogradely labeled profiles from thre e rats, 52 (33%) were apposed by DOR1-ir varicosities. We conclude tha t both mu- and delta-opioid receptors could be involved in the antinoc iception mediated by the PAG-RVM-spinal cord circuit. In addition, opi oids seem likely to have both direct and indirect effects on spinally projecting RVM cells in general, and on serotonergic RVM cells in part icular.