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 degrees C) of varying duration on the antinociceptive effects of morphine in mice. It was found that after 15 min exposure to cold significant endogenous analgesia was observed, together with a significant potentiation of the antinociceptive effects of morphine. However, after more prolonged exposure to 4 degrees C, the endogenous analgesia was no longer seen and, in addition, the antinociceptive effects of morphine diminished progressively, and after 2 h or longer exposure it was significantly less than control values. It was sown that, 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. It was also shown that the potency of morphine in adrenalectomized mice was not affected by 3 h cold stress. It is concluded that adrenal corticoids, released in response to the stressor effect of exposure to cold, are responsible for the antagonism of the antinociceptive action of morphine seen in mice after extended exposure to cold. It is suggested that the initial potentiation of the antinociceptive potency of morphine is 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.

Foot Shock Analgesia

“…Among the stressors capable of eliciting such an analgesic response are inescapable foot shock [10,14,22], cold water swimming [6,8,9], immobilisation [34] and centrifugal rota tion [ 14], The wide variety and the non-specific nature of the stressors which have been shown to produce analgesia is consistent with the existence of an endogenous pain-inhibit ing system [3,17,29], which presumably remains inactive most of the time, but is brought into action in response to severe stress.…”

“…Such changes in pain threshold following foot shock are in general agreement with previous studies [10,14,22]; exact comparisons of the magnitude of the changes is diffi cult in the light of differences in animal species, age, sche dule of stressing and the analgesic index chosen. There is some evidence suggesting that the degree and duration of analgesia produced by stress is directly proportional to the intensity, and inversely to the length, of stressors applied [14,22,34], On the one hand, SI A, unlike that produced by parenter al morphine administration, has been found to inhibit pain perception selectively, without producing generalised im pairment in sensory, motor or conscious state [14,22]; and on the other hand, analgesia produced by both stress and morphine is uniformly attenuated or abolished by naloxone treatment [7,22,34], In subsequent studies [Lim et al" unpubl. results] carried out in this laboratory under experi mental conditions identical to those used in the present report, naloxone (3 and 10 mg/kg) given intraperitoneally 30 min before the hot plate test substantially inhibited foot shock-induced analgesia (control 14.9 ± 0.9 s; 3 mg/kg na loxone 8.5 ± 0.8 (p < 0.001); 10 mg/kg naloxone 7.9 ± 0.7 (p < 0.001) (mean ± SEM).…”

“…Among many other features, stress-induced analgesia (SIA) possesses two salient characteristics: it is partially abolished by naloxone [3,7,13,22,34], and it is significant ly attenuated by hypophysectomy [9,13,30], Although the exact mechanisms underlying SIA are unclear, it appears to involve endogenous opiates and pituitary peptides, at least in part.…”

Brief Footshock Analgesia: Long-Lasting Enhancement Induced by Cathinone, an Amphetamine-Like Agent

“…With the exception of opioid [3,17,34,35], few studies have evaluated the recip rocal influence of stressors and drugs on analgesia. In the hot-plate test (HPT) in mice, cathinone [(-)-aminopropiophenone, CATH], a naturally occurring amphetamine like compound [23], induces a weak and brief analgesic effect, while in the tail-flick test (TFT) in rats an inhibition of pain per ception lasting for several days occurs [31].…”

Prolonged Foot-Shock Induced Analgesia: Glucocorticoids and Non-Pituitary Opioids Are Involved

“…tolerance to morphine [1,2,4,7,13,21]; on the other hand, hypophysectomy abolishes stress-induced analgesia [6,14] while enhancing morphine-induced analgesia [11,18]. The present study addresses two related questions -whether pi tuitary levels of immunoreactive cor relate with the analgesic responses elicited by prolonged foot-shock, and whether corticosteroids may have a differ ential effect on prolonged foot-shock analgesia and mor phine-induced analgesia, given their postulated critical role in opioid mediated forms of stress-indiced analgesia [16].…”