Mechanisms of Oxytocins Analgesia in Older Adults

老年人催产素镇痛机制

• 批准号: 10394186
• 负责人: Yenisel Cruz-Almeida
• 金额: $ 32.79万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10394186
• 关键词: Absence of pain sensation; Affect; Aging; Analgesics; Animals; Autonomic nervous system; Biological Markers; Brain; Brain imaging; Brain region; C-reactive protein; Characteristics; Choline; Chronic; Clinical; Clinical assessments; Cognitive; Creatine; Data; Degenerative polyarthritis; Discipline of obstetrics; Double-Blind Method; Elderly; Florida; Future; Goals; Human; Hypothalamic structure; Immune; Immune Plasma; Immune system; Immunologic Markers; Individual; Inflammation; Inflammatory; Inositol; Institutes; Interleukin-10; Interleukin-6; Intranasal Administration; Investigation; Joints; Knee; Knee Osteoarthritis; Magnetic Resonance Spectroscopy; Measurement; Measures; Mediator of activation protein; Methods; Modeling; Neuraxis; Neurons; Neuropeptides; Oxytocin; Oxytocin Receptor; Pain; Pain Management Method; Pain intensity; Pain management; Participant; Patient Self-Report; Patients; Performance; Peripheral; Physical Function; Pituitary Gland; Placebos; Plasma; Population; Prevalence; Process; Property; Protons; Psychosocial Factor; Research; Research Design; Safety; Self Administration; Severities; Standardization; Symptoms; System; TNF gene; Universities; Work; addiction liability; aged; base; biopsychosocial; chronic pain; chronic painful condition; clinical pain; cognitive function; cytokine; disability; effective therapy; emotional functioning; experience; human old age (65+); in vivo; inflammatory pain; inter-individual variation; intervention participants; joint injury; multimodality; neurobiological mechanism; novel; osteoarthritis pain; pain processing; pain relief; pain sensitivity; performance based measurement; response; stem; treatment optimization; treatment response

ABSTRACT Osteoarthritis (OA) represents a significant cause of disability worldwide in individuals aged 65 and older, a rapidly growing segment of our population. The knee is the most commonly affected joint with pain being the primary symptom, negatively impacting physical, cognitive, and emotional functioning. Symptomatic knee OA has been traditionally attributed to peripheral mechanisms, but measures of joint damage only modestly account for the presence or severity of OA-related pain. The neuropeptide oxytocin (OT) has been recognized as a mediator of endogenous analgesia in animal and human studies. However, little is known about the neurobiological mechanisms underlying OT's pain-relieving properties. This proposal is based on a mechanistic model of OT's analgesic effects leveraging pilot data supporting efficacy and safety of self-administered intranasal OT over 4-weeks in older individuals. Relative to placebo (P), daily administration of intranasal OT diminished self-reported pain intensity, reduced experimental pain sensitivity, and increased self-reported physical and emotional functioning. Further, participants treated with OT, compared to P, showed decreases in brain metabolite concentrations associated with inflammation. Thus, our overarching goal is to evaluate the effects of intranasal OT on pain and function in aging and to determine the extent to which central and peripheral inflammatory mechanisms contribute to these analgesic responses. We aim to 1) determine the effect of intranasal OT administration on clinical and experimental pain sensitivity in older adults with symptomatic knee OA and 2) characterize inflammatory mechanisms contributing to the inter-individual variability in analgesic responses to OT. Older adults with symptomatic knee OA will self-administer intranasal OT or P over 4 weeks using a double-blinded, parallel study design. With strong support from the University of Florida and the McKnight Brain Institute, our interdisciplinary project, using a comprehensive multi-methods approach, will be the first to determine the potential benefit of OT as a novel analgesic therapy for knee OA pain in aging. OT is currently used in obstetrics and may be an inexpensive, effective method for pain management in older adults with little potential for addiction. Embedded in a biopsychosocial framework, our proposal will help pave the way for future investigations using a mechanism-based treatment optimization strategy for individuals suffering from chronic pain.

抽象的 骨关节炎（OA）代表了65岁及以上的个体全球残疾的重要原因， 我们人口的迅速增长。膝盖是最常见的关节，疼痛是 主要症状，对身体，认知和情绪功能产生负面影响。有症状的膝盖OA 传统上一直归因于外围机制 对于OA相关疼痛的存在或严重程度。神经肽催产素（OT）已被认为是一种 动物和人类研究中内源性镇痛的介体。但是，关于 OT的疼痛舒张特性的神经生物学机制。该建议基于机械 OT的镇痛效应的模型利用了支持自我管理的功效和安全性的试验数据 年龄较大的人超过4周的鼻内。相对于安慰剂（P），每日鼻内OT给药 自我报告的疼痛强度降低，实验疼痛敏感性降低并自我报告增加 身体和情感功能。此外，与P相比，用OT处理的参与者显示出下降 脑代谢物浓度与炎症有关。因此，我们的总体目标是评估 鼻内OT对衰老疼痛和功能的影响，并确定中央和周围的程度 炎症机制有助于这些镇痛反应。我们的目的是1）确定 有症状的膝盖的老年人临床和实验性疼痛敏感性的鼻内OT给药 OA和2）表征有助于镇痛性变异性的炎症机制 对OT的响应。有症状的膝关节OA的老年人会在4周内自我助攻或P 使用双盲，并行研究设计。在佛罗里达大学和麦克奈特大学的大力支持下 我们的跨学科项目Brain Institute使用全面的多方法方法将是第一个 确定OT作为一种新型镇痛疗法的潜在益处，以使衰老中的膝关节疼痛。 OT当前是 用于妇产科 成瘾的潜力。我们的建议嵌入了生物心理社会框架中，将有助于为未来铺平道路 使用基于机制的治疗优化策略进行调查，为患有慢性的个体 疼痛。