AGE-RELATED CHANGES IN SPINAL OPIATE-INDUCED ANALGESIA

脊髓阿片引起的镇痛效果与年龄相关的变化

• 批准号: 3453572
• 负责人: TERRIANN CRISP
• 金额: $ 9.49万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3453572
• 关键词: aging; analgesics; drug addiction antagonist; electrochemistry; endorphins; heat injury; high performance liquid chromatography; juvenile animal; laboratory rat; mature animal; neurochemistry; neuropharmacology; neurotransmitter metabolism; norepinephrine; opiate alkaloid; opioid receptor; pain; serotonin; spinal block; spinal cord; stimulant /agonist

Endogenous serotonin (5-HT) and norepinephrine (NE) comprise the descending pain-inhibitory system, which modulates spinal nociceptive input. Monoamine oxidase (MAO) metabolizes endogenous 5-HT and NE, and recent studies have demonstrated that MAO activity in the brain increases with age. The present experiments are designed to investigate age-related differences in the perception of pain and spinal opiate- induced antinociception in young,mature and aged rats. Initial studies will investigate the effects of aging on the perception of thermally- mediated nociceptive stimuli in 6, 16 and 26 month old male Fischer 344 rats. Nociceptive will be measured using the tail-flick and hot plate analgesiometric assays. In Specific Aim#2, a neurochemical analysis will be made of the spinal levels of 5-HT, NE, dopamine and their respective metabolites in cervical, thoracic, and lumber and sacral spinal cord segments of 6, 16 and 26 month old rats. The neurochemical studies will be conducted using HPLC coupled with electrochemical detection. The studies comprising Specific Aim #3 will investigate age-related changes in the spinal antinociceptive efficacy of DAMPGO (a m agonist), DPDPE (a delta agonist) and Beta-endorphin (an epsilon opioid receptor agonist) in young, mature and aged rats. The tail-flick and hot plate analgesiometric tests will be used to measure opiate-induced spinal analgesia. Lastly, Specific Aim #4 will assess age-related differences in the role of spinal mu, delta and epsilon opioid receptor subtypes in the spinal antinociceptive effects of DAMPGO, DPDPE and Beta-endorphin. In these studies, 6, 16 and 26 month old rats will receive i.t. pretreatments with a receptor-selective mu, delta or epsilon opiate antagonist (CTP-NH2, naltrindole or Beta-endorphin 1-27, respectively) prior to a fixed antinociceptive dose of i.t. DAMPGO, DPDPE or Beta- endorphin. The inhibitory efficacy of each receptor antagonist against each opiate agonist will be determined in young, mature and aged rats, and ID50 values will be generated. These studies will further identify the relevant opioid receptor subtype(s) in the spinal cord responsible for mediating opiate-induced antinociceptive as a function of age.

内源性血清素 (5-HT) 和去甲肾上腺素 (NE) 组成 下行疼痛抑制系统，调节脊髓伤害感受 输入。单胺氧化酶 (MAO) 代谢内源性 5-HT 和 NE，并且 最近的研究表明，大脑中的 MAO 活性 随着年龄的增长。本实验旨在研究 对疼痛和脊髓阿片类药物的感知与年龄相关的差异 在年轻、成熟和老年大鼠中诱导抗伤害作用。初步研究 将研究衰老对热感知的影响 6、16 和 26 个月大的雄性 Fischer 介导的伤害性刺激 344 老鼠。将使用甩尾和热板测量伤害感受 镇痛测定。在特定目标#2 中，神经化学分析将 由5-HT、NE、多巴胺及其各自的脊髓水平组成 颈椎、胸椎、腰椎和骶椎脊髓中的代谢物 6、16 和 26 个月大的大鼠的片段。神经化学研究将 使用 HPLC 结合电化学检测进行。这 包括具体目标#3在内的研究将调查与年龄相关的变化 DAMPGO（一种激动剂）、DPDPE（一种 δ 激动剂）和 β-内啡肽（ε 阿片受体激动剂） 在年轻、成熟和老年大鼠中。甩尾和热板 镇痛测试将用于测量阿片类药物引起的脊髓损伤 镇痛。最后，具体目标 #4 将评估与年龄相关的差异 脊髓 mu、delta 和 epsilon 阿片受体亚型的作用 DAMPGO、DPDPE 和 Beta-内啡肽的脊髓镇痛作用。 在这些研究中，6、16 和 26 个月大的老鼠将接受它。 使用受体选择性 mu、delta 或 epsilon 阿片剂进行预处理 拮抗剂（分别为 CTP-NH2、纳曲吲哚或 β-内啡肽 1-27） 在使用固定的抗伤害剂量的 i.t. 之前DAMPGO、DPDPE 或 Beta- 内啡肽。各受体拮抗剂的抑制效果 每种阿片激动剂都将在年轻、成熟和老年大鼠中进行测定， 将生成 ID50 值。这些研究将进一步确定 脊髓中相关的阿片受体亚型负责 用于调节阿片类药物引起的镇痛作用作为年龄的函数。