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Advanced age attenuates the antihyperalgesic effect of morphine and decreases μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray in male and female rats
Neurobiology of Aging ( IF 4.2 ) Pub Date : 2021-02-01 , DOI: 10.1016/j.neurobiolaging.2020.10.020
Evan F Fullerton 1 , Myurajan Rubaharan 1 , Mary C Karom 1 , Richard I Hanberry 1 , Anne Z Murphy 1
Affiliation  

The present study investigated the impact of advanced age on morphine modulation of persistent inflammatory pain in male and female rats. The impact of age, sex, and pain on μ-opioid receptor (MOR) expression and binding in the ventrolateral periaqueductal gray (vlPAG) was also examined using immunohistochemistry and receptor autoradiography. Intraplantar administration of complete Freund's adjuvant induced comparable levels of edema and hyperalgesia in adult (2-3 mos) and aged (16-18 mos) male and female rats. Morphine potency was highest in adult males, with a greater than two-fold increase in morphine EC50 observed in adult versus aged males (3.83 mg/kg vs. 10.16 mg/kg). Adult and aged female rats also exhibited significantly higher EC50 values (7.76 mg/kg and 8.74 mg/kg, respectively) than adult males. The upward shift in EC50 from adult to aged males was paralleled by a reduction in vlPAG MOR expression and binding. The observed age-related reductions in morphine potency and vlPAG MOR expression and binding have significant implications in pain management in the aged population.

中文翻译:

高龄会减弱吗啡的抗痛觉过敏作用并降低雄性和雌性大鼠中脑导水管周围灰质中μ-阿片受体的表达和结合

本研究调查了高龄对吗啡调节雄性和雌性大鼠持续性炎症疼痛的影响。还使用免疫组织化学和受体放射自显影检查了年龄、性别和疼痛对腹外侧导水管周围灰质 (vlPAG) 中 μ-阿片受体 (MOR) 表达和结合的影响。足底内施用完全弗氏佐剂在成年(2-3 个月)和老年(16-18 个月)雄性和雌性大鼠中诱导相当水平的水肿和痛觉过敏。吗啡的效力在成年男性中最高,成年男性与老年男性相比,吗啡 EC50 增加了两倍以上(3.83 mg/kg 对 10.16 mg/kg)。成年和老年雌性大鼠的 EC50 值也显着高于成年雄性大鼠(分别为 7.76 mg/kg 和 8.74 mg/kg)。EC50 从成年男性到老年男性的上移与 vlPAG MOR 表达和结合的减少平行。观察到的吗啡效力和 vlPAG MOR 表达和结合与年龄相关的降低对老年人群的疼痛管理具有重要意义。
更新日期:2021-02-01
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