Comparison of the antinociceptive action of mu and delta opioid receptor ligands in the periaqueductal gray matter, medial and paramedial ventral medulla in the rat as studied by the microinjection technique.

In rats stereotaxically implanted with microinjection cannula in either the periaqueductal gray matter (PAG) or the medial/paramedial medullary reticular formation (MRF), microinjection of morphine, sufentanil, D-Ala2-D-Leu5-enkephalin (DADL) or D-Ser2-Thr6-leucine enkephalin (DSTLE) produced dose-dependent elevations in the response latency on tail-flick and hot plate tests. These effects were reversed by naloxone administered by microinjection into the same intracerebral site. Both mu (morphine and sufentanil) and delta (DADL and DSTLE) opioid receptor ligands produced a maximal elevation in the supraspinally mediated hot plate response when administered into either the PAG or the MRF. Similarly, mu and delta receptor ligands produced maximum elevations in the spinally mediated tail-flick response when microinjected into the PAG. In contrast, delta, but not mu, receptor agonists produced a total blockade of the tail-flick response following administration into the MRF. Microinjection of mu (morphine) or delta (DADL) agonists into the PAG or the MRF also resulted in a naloxone-reversible inhibition of the visceral chemical evoked writhing response. These observations suggest that mu and delta opioid receptor linked systems within the MRF but not the PAG produce their antinociceptive effects by discriminable mechanisms with a differential action on spinopetal vs supraspinal modulatory systems.