EFFECTS OF MU-OPIOID, DELTA-OPIOID AND KAPPA-OPIOID ANTAGONISTS ON THE DEPRESSION OF A C-FIBER REFLEX BY INTRATHECAL MORPHINE AND DAGO IN THE RAT

The roles of mu, delta and kappa opioid receptor subtypes in spinal morphine-induced antinociception were investigated. A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. Recruitment curves were built by varying the stimulus intensity from 0 to 7x threshold and temporal evolutions were studied by using a constant level of stimulus intensity (3x threshold). Intrathecal administration of naloxone, Cys(2)-Tyr(3)-Orn(5)-Pen(7) amide (mu opioid receptor antagonist) and nor-binaltorphimine (nor-BNI, a kappa opioid receptor antagonist) completely antagonized the depression of the C-fiber reflex induced by 4 nmol of intrathecal morphine, whereas the antagonistic effect of naltrindole (a delta receptor antagonist) was limited, with a ceiling effect of 56%. The AD(50) were 12 pmol and 1, 4.3 and 39 nmol for Cys(2)-Tyr(3)-Orn(5)-Pen(7) amide, naloxone, nor-BNI and naltrindole, respectively. When injected alone, only naltrindole induced a short-duration depressive effect, Intrathecal administration of DAGO resulted in a depressive effect on the C-fiber reflex in a dose-dependent manner; for a stimulus intensity of 3x threshold, the ED(50) was 9 pmol. DAGO was found to be 60 times more potent than morphine. Interestingly, nor-BNI, at doses which reversed the blockade of the C-fiber reflex by morphine, also reversed the effects of an equipotent dose of DAGO, which suggested an action on a mu receptor subtype.