Involvement of N-methyl-D-aspartate receptors and nitric oxide in the rostral ventromedial medulla in modulating morphine pain-inhibitory signals from the periaqueductal grey matter in rats.

1. Supraspinal opioid antinociception is mediated, in part, by connections between the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM). Morphine antinociception from the PAG is decreased by serotonin, N-methyl-d-aspartate (NMDA) and opioid receptor antagonists administered into the RVM. Because the brain isoform of nitric oxide synthase (NOS) is also prominent in the RVM, the present study was designed to evaluate the effects of microinjection of the non-selective NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the non-competitive NMDA receptor antagonist MK-801 into the RVM on PAG morphine antinociception and their potential interactions, as measured by the tail-flick test. 2. Rats were anaesthetized with sodium pentobarbital and then special cannulas were inserted stereotaxically into the RVM and PAG. After 1 week recovery, the effects of microinjection of MK-801 and l-NAME into the RVM and their interactions in altering PAG morphine (2.5 microg) antinociception elicited from the PAG were assessed. 3. Mesencephalic morphine antinociception was significantly reduced after pretreatment with l-NAME (0.6-1.3 micromol) or MK-801 (0.8 nmol). The reduction in mesencephalic morphine antinociception when MK-801 (0.8 nmol) and l-NAME (1 micromol) were microinjected sequentially into the RVM was not significantly different from the effects of MK-801 (0.8 nmol) or l-NAME (1 micromol) administered alone. 4. These data imply that NMDA receptors and nitric oxide production in the RVM modulate the transmission of opioid pain-inhibitory signals from the PAG.