Mechanisms of Oxytocins Analgesia in Older Adults

摘要 骨关节炎(OA)是全球65岁及以上人群残疾的一个重要原因， 在我们人口中迅速增长的部分。膝关节是最常受影响的关节，疼痛是 主要症状，对身体、认知和情绪功能产生负面影响。症状性膝骨性关节炎 传统上被归因于外周机制，但关节损伤的衡量标准仅适度考虑 对于与骨关节炎相关的疼痛的存在或严重程度。神经肽催产素(OT)被认为是一种 动物和人类研究中的内源性镇痛的中介物。然而，人们对此知之甚少 OT止痛特性背后的神经生物学机制。这个建议是建立在机械论的基础上的 利用先导数据支持自身给药的有效性和安全性的OT止痛作用模型 4周以上老年人鼻腔注射催产素。相对于安慰剂(P)，每天鼻内注射催产素 减少自我报告的疼痛强度，降低实验性疼痛敏感度，增加自我报告的疼痛强度 生理和情感功能。此外，与P相比，接受OT治疗的参与者显示出 脑部代谢物浓度与炎症有关。因此，我们的首要目标是评估 鼻腔催产素对衰老患者疼痛和功能的影响以及确定中枢和外周功能的程度 炎症机制促成了这些止痛反应。我们的目标是1)确定 OT鼻腔给药对有膝关节症状的老年人的临床和实验疼痛敏感性的影响 OA和2)表征导致止痛药个体间差异的炎症机制 对OT的响应。有症状的膝骨性关节炎的老年人将在4周内自行鼻内注射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基金会的大力支持下 脑研究所，我们的跨学科项目，使用综合的多方法方法，将是第一个 确定OT作为老年性膝骨性关节炎疼痛的一种新型止痛疗法的潜在益处。加班费目前 用于产科，可能是一种廉价、有效的老年人疼痛控制方法 可能会上瘾。嵌入生物心理社会框架，我们的建议将有助于为未来铺平道路 采用基于机制的治疗优化策略对慢性阻塞性肺疾病患者进行调查 疼痛。

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.