Impact of advanced age on opiate analgesia

高龄对阿片类镇痛的影响

• 批准号: 9247629
• 负责人: ANNE Z MURPHY
• 金额: $ 35.98万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9247629
• 关键词: Absence of pain sensation; Accounting; Address; Adjuvant; Adult; Affinity; Age; Analgesics; Animals; Arthritis; Attenuated; Autoradiography; Behavioral; Belief; Binding; Biological; Biological Assay; Brain; Cell Death; Cells; Clinical Research; Communities; Consensus; Data; Development; Disease; Dose; Effectiveness; Elderly; Evaluation; Family; Female; Fostering; Foundations; G-substrate; GTP-Binding Protein Regulators; GTP-Binding Proteins; Genetic Transcription; Goals; Grant; Guanosine Triphosphate Phosphohydrolases; Guidelines; In Situ Hybridization; Individual; Inflammatory; Knowledge; Longevity; Measures; Mediating; Membrane Lipids; Messenger RNA; Midbrain structure; Modeling; Molecular; Morphine; Neurobiology; Opiates; Opioid; Opioid Analgesics; Output; Pain; Pain management; Peripheral; Peripheral Nervous System Diseases; Persistent pain; Persons; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Physiological; Population; Process; Property; Proteins; Rattus; Receptor Signaling; Regulation; Reporting; Signal Transduction; Signaling Protein; Site; Societies; Stomach; System; Target Populations; Techniques; Testing; Viral Vector; age related; aged; base; central pain; chronic pain; clinically relevant; evidence base; experience; experimental study; improved; inflammatory pain; mRNA Expression; male; member; midbrain central gray substance; mu opioid receptors; multidisciplinary; neural circuit; novel; opioid use; receptor; receptor binding; receptor coupling; receptor expression; response; somatosensory; standard care; treatment strategy

ABSTRACT The goal of these studies is to understand the impact of advanced age on opiate modulation of persistent pain. In 2013, people aged 65 and older represented 14.1% of the US population. These numbers are expected to rise dramatically, with person’s aged 65 years or older accounting for 20- 30% of the total population by 2030. Unfortunately, one of the consequences of increased longevity is pain, with 45-85% of the population aged 65 or older experiencing pain on a daily basis. Unfortunately, chronic pain is under-treated for the majority of elderly persons. A primary factor contributing to the under management of pain is the dearth of knowledge on the impact of age on pain and opiate sensitivity. Indeed, a recent consensus statement issued by a multidisciplinary group of pain experts states: “The paucity of guidelines for opioid use in the elderly reflects the lack of studies of these drugs on the old.” A clear understanding of age-associated changes in opioidergic circuits of males and females is critical for evidence-based pain management in this population. Our behavioral data indicate that the antihyperalgesic effect of morphine is significantly attenuated in aged (18-24 mos) versus adult (2-3 mos) rats. Indeed, the ED50 dose for aged animals is 7.0 mg/kg in comparison to 3.5 mg/kg for adults. Our overarching hypothesis is that age- induced changes in mu opioid receptor expression and signaling within the midbrain periaqueductal gray (PAG) provide the biological bases for the decreased sensitivity to opiates observed in the elderly. Three specific aims are proposed to determine the influence of advanced age on mu opioid receptor expression and receptor pharmacodynamics (SA1) and G protein receptor coupling and regulation (SA2). Aim 3 will use molecular and pharmacological techniques to boost central MOR signaling, thereby reducing morphine dosing requirements. Together, these studies will provide novel and critical data on the impact of age on opiate effectiveness, and will stimulate evidence-based therapies for the management of pain in the elderly.

抽象的 这些研究的目的是了解高龄对阿片类药物调节的影响 2013年，65岁及以上的人占美国人口的14.1%。 预计这一数字将急剧上升，其中 65 岁或以上的人占 20- 到 2030 年，这一数字将占总人口的 30%。不幸的是，寿命延长的后果之一是 疼痛是一种疼痛，65 岁或以上的人口中有 45-85% 每天都会经历疼痛。 不幸的是，大多数老年人的慢性疼痛得不到充分治疗。 导致疼痛管理不善的原因是对年龄对疼痛的影响了解的深入。 事实上，多学科最近发表了一份共识声明。 疼痛专家小组表示：“老年人使用阿片类药物的指南的缺乏反映出缺乏 这些药物对老年人的研究。” 男性和女性的阿片样物质回路对于循证疼痛管理至关重要 我们的行为数据表明吗啡的抗痛觉过敏作用显着。 与成年（2-3 个月）大鼠相比，老年（18-24 个月）大鼠的 ED50 剂量确实减弱。 动物的摄入量为 7.0 毫克/公斤，而成人的摄入量为 3.5 毫克/公斤。 诱导中脑内 mu 阿片受体表达和信号传导的变化 导水管周围灰质（PAG）为阿片类药物敏感性降低提供了生物学基础 提出了三个具体目标来确定高级的影响。 年龄对μ阿片受体表达及受体药效学（SA1）和G蛋白的影响 目标 3 将使用分子和药理学技术。 增强中枢 MOR 信号传导，减少吗啡剂量需求，从而实现这些。 研究将提供关于年龄对阿片类药物有效性影响的新颖且关键的数据，并将 刺激治疗老年人疼痛的循证疗法。