MODULATION OF NOCICEPTION BY MICROINJECTION OF DELTA-1 AND DELTA-2 OPIOID RECEPTOR LIGANDS IN THE VENTROMEDIAL MEDULLA OF THE RAT

In this study, we characterized the role of delta-1 and delta-2 opioid receptors in the ventromedial medulla (VMM) in the modulation of ther mal nociception. Male Sprague-Dawley rats were prepared with an intrac erebral guide cannula aimed at the nucleus raphe magnus or nucleus ret icularis gigantocellularis pars a. Microinjection of the delta-1 opioi d receptor agonist [D-Pen(2),D-Pen(5)]enkephalin (DPDPE) or the delta- 2 opioid receptor agonist [o-Ala(2),Glu(4)]deltorphin (DELT) in the VM M increased response latency in the radiant heat tail-flick test with respective ED50 values (95% CL) of 0.66 (0.07-1.5) nmol and 0.1 (0.03- 0.21) nmol. In the 55 degrees C hot-plate test, DELT produced a modest , transient increase in response latency and DPDPE was ineffective. Th e antinociception produced by DPDPE was antagonized by microinjection at the same site of 1.5 pmol of the delta-1 opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) but not by 0.15 nmol of the delta-2 op ioid receptor antagonist naltriben (NTB). Conversely, the antinocicept ion produced by DELT was antagonized by microinjection at the same sit e of 0.15 nmol of NTB but not by 1.5 pmol of BNTX. These doses of BNTX or NTB alone did not alter either tail-flick or hot-plate latency whe n microinjected in the VMM. However, at IO-fold higher doses, BNTX los t its selectivity for the delta-1 opioid receptor, and NTB by itself i ncreased tail-flick and hot-plate latencies. These results collectivel y implicate both delta-1 and delta-2 opioid receptors in the VMM in th e modulation of nociception. They also indicate that the antinocicepti ve effects of DPDPE and DELT can be distinguished by BNTX and NTB, pro viding additional support for the existence of delta-1 and delta-2 opi oid receptor subtypes at supraspinal loci. Finally, the failure of eff ective doses of either BNTX or NTB to alter nociceptive threshold sugg ests that neurons in the VMM do not receive a tonic, inhibitory enkeph alinergic input mediated by delta-1 or delta-2 receptors.