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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。

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.

机构信息

Neuroscience Institute, Georgia State University, Atlanta, GA, USA.

Neuroscience Institute, Georgia State University, Atlanta, GA, USA.

出版信息

Neurobiol Aging. 2021 Feb;98:78-87. doi: 10.1016/j.neurobiolaging.2020.10.020. Epub 2020 Oct 27.

DOI:10.1016/j.neurobiolaging.2020.10.020
PMID:33249376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8673746/
Abstract

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 EC observed in adult versus aged males (3.83 mg/kg vs. 10.16 mg/kg). Adult and aged female rats also exhibited significantly higher EC values (7.76 mg/kg and 8.74 mg/kg, respectively) than adult males. The upward shift in EC 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.

摘要

本研究探讨了年龄对雄性和雌性大鼠持续性炎性疼痛中吗啡调节的影响。还使用免疫组织化学和受体放射自显影术研究了年龄、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。完全弗氏佐剂的足底注射在成年(2-3 个月)和老年(16-18 个月)雄性和雌性大鼠中引起了可比的水肿和痛觉过敏水平。吗啡效力在成年雄性中最高,成年雄性的吗啡 EC 值增加了两倍以上(3.83mg/kg 比 10.16mg/kg)。成年和老年雌性大鼠的 EC 值也明显高于成年雄性(分别为 7.76mg/kg 和 8.74mg/kg)。从成年到老年雄性的 EC 值上移与 vlPAG MOR 表达和结合的减少平行。观察到的与年龄相关的吗啡效力降低以及 vlPAG MOR 表达和结合的减少对老年人群的疼痛管理具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/1ad0cd472f97/nihms-1641421-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/450672be97a7/nihms-1641421-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/e5ab22a38a8b/nihms-1641421-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/ab224b7f919e/nihms-1641421-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/1ad0cd472f97/nihms-1641421-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/450672be97a7/nihms-1641421-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/e5ab22a38a8b/nihms-1641421-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/ab224b7f919e/nihms-1641421-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc4/8673746/1ad0cd472f97/nihms-1641421-f0005.jpg

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