Nelson C J, Dykstra L A, Lysle D T
Department of Psychology, University of North Carolina at Chapel Hill, 27599-3270, USA.
Anesth Analg. 1997 Sep;85(3):620-6. doi: 10.1097/00000539-199709000-00024.
Morphine, an opioid analgesic commonly prescribed and abused, produces immune-altering effects. Whether morphine's antinociceptive and immunologic effects occur concurrently is unknown. Therefore, we investigated the time course of morphine's immunologic and antinociceptive effects. Rats were given a 15-mg/kg morphine injection (subcutaneously), and experimental assessments were taken at 30 min, 1 h, 2 h, 6 h, 12 h, and 24 h after treatment. Immune measures included natural killer (NK) cell activity, proliferation of splenic T and B lymphocytes, and cytokine production. Antinociception was assessed by using the tail withdrawal assay. Results show that morphine's immunomodulatory effects on NK cell activity begin within 30 min, continue for at least 12 h, and return to control values by 24 h. In contrast, proliferation of splenic T and B cells and interferon-gamma production are not altered within 30 min; maximal suppression occurs at 1 h, and recovery begins within 2 h. In all immune measures, therefore, maximal suppression is present at the 1-h time point, and recovery is complete within 24 h. Morphine induces antinociception 30 min to 2 h after drug administration; recovery is complete within 6 h. These results suggest the possibility that different mechanisms modulate morphine's immunologic and analgesic effects.
Acute morphine treatment in rats produces immune alterations and antinociception. Although there are slight differences in morphine's maximal immunological and antinociceptive effects, morphine suppresses immune status at time points concordant with its antinociceptive effects. These effects should be considered when administering morphine to patients whose systems are immunocompromised.
吗啡是一种常用且易被滥用的阿片类镇痛药，具有免疫调节作用。吗啡的镇痛作用和免疫作用是否同时发生尚不清楚。因此，我们研究了吗啡免疫和镇痛作用的时间进程。给大鼠皮下注射15mg/kg吗啡，并在给药后30分钟、1小时、2小时、6小时、12小时和24小时进行实验评估。免疫指标包括自然杀伤（NK）细胞活性、脾T和B淋巴细胞增殖以及细胞因子产生。通过甩尾试验评估镇痛效果。结果表明，吗啡对NK细胞活性的免疫调节作用在30分钟内开始，至少持续12小时，并在24小时恢复到对照值。相比之下，脾T和B细胞的增殖以及干扰素-γ的产生在30分钟内没有改变；最大抑制在1小时出现，恢复在2小时内开始。因此，在所有免疫指标中，最大抑制在1小时时间点出现，恢复在24小时内完成。吗啡在给药后30分钟至2小时诱导镇痛；6小时内恢复完全。这些结果提示，可能有不同机制调节吗啡的免疫和镇痛作用。
大鼠急性吗啡治疗可产生免疫改变和镇痛作用。虽然吗啡的最大免疫和镇痛作用存在细微差异，但吗啡在与镇痛作用一致的时间点抑制免疫状态。在给免疫功能低下的患者使用吗啡时应考虑这些作用。
