Stress reduces morphine's antinociceptive potency: dependence upon spinal cholecystokinin processes

The antinociceptive potency of opioids is altered by stress. We have shown that repetitive exposure of rats to noxious heat produced stress-induced analgesia as detected by the tail-flick test, but decreased the potency of the opioid beta-endorphin in the periaqueductal gray region of the midbrain (PAG). In this study, we examined the effects of this same stressor on the antinociceptive actions of the alkaloid narcotic, morphine, following either i.p. or intracerebral administration. Regardless of the route of administration, a significant reduction in the narcotic's ability to produce antinociception during stress was observed. The stress-induced reduction in morphine's potency was reversed by the intrathecal administration of the cholecystokinin (CCK) receptor antagonist L-365,260 (0.1 ng per rat), suggesting that spinal CCK-dependent 'anti-analgesic' processes are involved. Since stress influences the potency of narcotics, it may be an important physiological component to be considered in the clinical management of pain. Moreover, CCK receptor antagonists may improve the reliability of narcotic therapy.