title: Modulation of nociception by microinjection of delta-1 and delta-2 opioid receptor ligands in the ventromedial medulla of the rat.
abstract: In this study, we characterized the role of delta-1 and delta-2 opioid receptors in the ventromedial medulla (VMM) in the modulation of thermal nociception. Male Sprague-Dawley rats were prepared with an intracerebral guide cannula aimed at the nucleus raphe magnus or nucleus reticularis gigantocellularis pars alpha. Microinjection of the delta-1 opioid receptor agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) or the delta-2 opioid receptor agonist [D-Ala2, Glu4]deltorphin (DELT) in the VMM 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. The 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 opioid receptor antagonist naltriben (NTB). Conversely, the antinociception produced by DELT was antagonized by microinjection at the same site 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 when microinjected in the VMM. However, at 10-fold higher doses, BNTX lost its selectivity for the delta-1 opioid receptor, and NTB by itself increased tail-flick and hot-plate latencies. These results collectively implicate both delta-1 and delta-2 opioid receptors in the VMM in the modulation of nociception. They also indicate that the antinociceptive effects of DPDPE and DELT can be distinguished by BNTX and NTB, providing additional support for the existence of delta-1 and delta-2 opioid receptor subtypes at supraspinal loci. Finally, the failure of effective doses of either BNTX or NTB to alter nociceptive threshold suggests that neurons in the VMM do not receive a tonic, inhibitory enkephalinergic input mediated by delta-1 or delta-2 receptors.
authors.affiliation: Department of Anesthesia and Critical Care, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Thorat
authors.forename: D L
authors.initials: DL
authors.lastname: Hammond
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D008845:Microinjections; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*
chemical_list: D000701:Analgesics, Opioid; D001597:Benzylidene Compounds; D004745:Enkephalins; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C060209:deltorphin II, Ala(2)-; C077358:7-benzylidenenaltrexone; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-