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.

摘要 骨关节炎（OA）是全球65岁及以上人群残疾的重要原因， 快速增长的部分人口。膝盖是最常见的受影响的关节，疼痛是最常见的。 主要症状，对身体、认知和情感功能产生负面影响。症状性膝关节OA 传统上归因于外周机制，但关节损伤的测量仅适度考虑 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 在动物和人体研究中内源性镇痛介质。然而，人们对此知之甚少。 OT缓解疼痛的神经生物学机制。这一建议是基于一种机械的 OT的镇痛作用模型，利用支持自我给药的有效性和安全性的试点数据 鼻内OT超过4周的老年人。相对于安慰剂（P），鼻内OT每日给药 自我报告的疼痛强度降低，实验性疼痛敏感性降低，自我报告的疼痛强度增加。 身体和情感功能。此外，与P相比，接受OT治疗的参与者显示， 与炎症相关的脑代谢物浓度。因此，我们的首要目标是评估 鼻内OT对疼痛和衰老功能的影响，并确定中枢和外周 炎症机制有助于这些镇痛反应。我们的目标是：1）确定 鼻内给予OT对有症状膝关节老年人临床和实验疼痛敏感性的影响 OA和2）表征有助于镇痛药个体间差异的炎症机制 回复OT。患有症状性膝关节OA的老年人将在4周内自我给予鼻内OT或P 采用双盲平行研究设计。在佛罗里达大学和麦克奈特大学的大力支持下， 大脑研究所，我们的跨学科项目，使用全面的多方法的方法，将是第一个 确定OT作为一种新型镇痛疗法治疗老年膝关节OA疼痛的潜在益处。目前， 用于产科，可能是一种廉价，有效的方法，用于老年人的疼痛管理， 成瘾的可能性。在生物心理社会的框架内，我们的建议将有助于为未来铺平道路。 使用基于机制的治疗优化策略对患有慢性疾病的个体进行的研究 痛苦