Opioid and non-opioid stress analgesia: assessment of tolerance and cross-tolerance with morphine.

Opioid and non-opioid mechanisms of analgesia elicited by two kinds of footshock stress that differ only in temporal characteristics previously have been inferred on the basis of susceptibility to naloxone blockade. The present study sought further evidence on this point by comparing these two kinds of footshock analgesia for possible tolerance development and cross-tolerance with morphine. It was found that, with repeated exposure to stress, tolerance developed to naloxone-sensitive, but not naloxone-insensitive, stress analgesia. Furthermore, morphine-tolerant rats displayed cross-tolerance to only the naloxone-sensitive form of footshock analgesia. Although prior exposure to both footshock paradigms potentiated morphine analgesia, less potentiation occurred in rats tolerant to the naloxone-sensitive footshock stress. Thus, cross-tolerance between morphine and this type of stress analgesia appears to occur in both directions. These findings are consistent with those using naloxone antagonism as a criterion for opioid mediation and support the conclusion that separate opioid and non-opioid mechanisms of stress analgesia exist.