The possibility that a component of morphine-induced analgesia is contributed indirectly via the release of endogenous opioids

Abstract

The abdominal constriction test was used to explore the effects of cold stress (4.degree. C) of varying duration on the antinociceptive effects of morphine in mice. After 15 min exposure to cold, significant endogenous analgesia was observed together with a significant potentiation of the antinociceptive effects of morphine. After more prolonged exposure to 4.degree. C, the endogenous analgesia was no longer seen, the antinociceptive effects of morphine diminished progressively and after 2 h or longer exposure it was significantly less than control values. In the absence of cold stress, pretreatment with corticosterone, dexamethasone or ACTH reduced the potency of morphine in a manner similar to that seen after 4 h cold stress. The potency of morphine in adrenalectomized mice was not affected by 3 h cold stress. Adrenal corticoids, released in response to the stressor effect of exposure to cold, apparently responsible for the antagonism of the antinociceptive action of morphine seen in mice after extended exposure to cold. The initial potentiation of the antinociceptive potency of morphine is possibly due to the release of endogenous opioids. With more prolonged stress, the stores of these substances may become progressively depleted, possibly as a result of raised corticosteroid levels, so that the component of analgesia contributed by them is steadily reduced and ultimately abolished.