Delta opioid receptor mediated actions in the rostral ventromedial medullaon tail flick latency and nociceptive modulatory neurons

The rostral ventromedial medulla (RVM) is critical for the modulation of do rsal horn nociceptive transmission. Three classes of RVM neurons (ON, OFF, and NEUTRAL) have been described that have distinct responses to noxious st imuli and mu opioid receptor (MOR) agonists. The present study in barbitura te anesthetized rats investigated the effects of the delta 2 opioid recepto r (DOR2) agonist, [D-Ala2]deltorphin II (DELT), microinfused into the RVM o n the tail flick reflex and activity of RVM neurons. Tail flick latencies i ncreased dose-dependently after administration of DELT (0.6 nmol and 1.2 nm ol). Furthermore, DELT inhibited the tail hick related increase in ON cell activity and shortened the tail flick related pause in OFF cell activity. T he activity of NEUTRAL cells was not affected. The antinociceptive effects and corresponding changes in ON and OFF cell activity produced by DELT were antagonized by the DOR2 antagonist, naltriben methanesulfonate, administer ed at the same site. These DOR2 mediated effects on noxious stimulation-evo ked changes in RVM neuronal activity are similar to those reported for MOR agonists and suggest that both DOR2 and MOR produce analgesia through activ ation of OFF cells. (C) 2000 International Association for the Study of Pai n. Published by Elsevier Science B.V. All rights reserved.