Adrenalectomy-induced potentiation of morphine analgesia: reversal by prednisolone
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Y Miyamoto1, M Ozaki, S Kishioka
1Department of Pharmacology, Wakayama Medical College, Japan.
Abstract:
Effects of adrenalectomy (ADX) on analgesic potency and morphine (MOR) content after SC administration of 3.5 or 7 mg/kg of MOR, and effects of prednisolone (PRED) on the ADX-induced effects were studied. ADX significantly potentiated MOR analgesia at both MOR doses, and PRED reversed the ADX-induced potentiation of MOR analgesia, ADX did not affect MOR content in brain and plasma after 3.5 mg/kg MOR, but significantly increased MOR content in brain and plasma after 7 mg/kg MOR, and PRED reversed the ADX-induced increase in the MOR content. Although the analgesic potency of 3.5 mg/kg MOR in ADX group was equipotent with those of 7 mg/kg MOR in sham-operated and PRED-treated ADX groups, MOR content in the former group was significantly lower than those in the latter two groups. These results suggest that ADX potentiates MOR analgesia through both mechanisms of the increased MOR content and the increased sensitivity to MOR, and that the lack of glucocorticoids participates in both of these ADX-induced effects.
Insights
Adrenalectomy (ADX) enhances morphine (MOR) analgesia and increases brain/plasma MOR levels, effects reversed by prednisolone (PRED). This suggests glucocorticoid deficiency impacts MOR efficacy through altered drug levels and sensitivity.
Area of Science:
- Pharmacology
- Endocrinology
- Neuroscience
Background:
- Adrenalectomy (ADX) removes the adrenal glands, impacting hormone levels.
- Glucocorticoids play a role in various physiological processes, including pain modulation.
- Morphine (MOR) is a primary opioid analgesic with complex pharmacokinetics and pharmacodynamics.
Purpose of the Study:
- To investigate the effects of adrenalectomy (ADX) on the analgesic potency and tissue content of morphine (MOR).
- To determine the influence of prednisolone (PRED), a synthetic glucocorticoid, on ADX-induced changes in MOR analgesia and levels.
- To elucidate the mechanisms underlying ADX-mediated alterations in MOR efficacy.
Main Methods:
- Rats underwent adrenalectomy (ADX) or sham surgery.
- Morphine (MOR) was administered subcutaneously at doses of 3.5 or 7 mg/kg.
- Analgesic potency was assessed, and MOR content was measured in brain and plasma.
- Prednisolone (PRED) was administered to ADX rats to evaluate its effects.
Main Results:
- ADX significantly potentiated MOR analgesia at both tested doses.
- ADX increased MOR content in brain and plasma, but only at the higher MOR dose (7 mg/kg).
- Prednisolone (PRED) administration reversed the potentiating effects of ADX on MOR analgesia and MOR content.
Conclusions:
- Adrenalectomy potentiates morphine analgesia through increased MOR content and enhanced sensitivity to MOR.
- The absence of glucocorticoids, following ADX, contributes to both increased MOR levels and heightened MOR efficacy.
- These findings highlight the crucial role of glucocorticoids in modulating opioid analgesia and pharmacokinetics.