Effects of Age on Thermal Sensitivity

描述（由申请人提供）：年龄增长如何影响负责疼痛体验的生物系统是疼痛研究领域的一个重大挑战。承认老年人的慢性疼痛在临床上、生物学上和治疗上都比年轻人群的疼痛复杂得多，这一事实强调了需要进行综合研究，包括行为变化和负责随着年龄增长疼痛感知改变的生物学机制。在过去的20年里，与疼痛的外周和中枢基质相关的知识已经取得了显着进展。不幸的是，几乎没有证据表明我们所学到的任何东西适用于老年人（动物或人类）的疼痛系统。对慢性疼痛发展的细胞和分子机制的研究揭示了与衰老机制的不可否认的重叠，从而为评估衰老生物学过程与慢性疼痛病理状态之间相互作用的研究提供了理论基础。三个具体目标有关的影响，年龄增长的热敏感性将得到解决，包括努力界定的时间特性的年龄相关的变化，热和冷的敏感性。热敏感性将采用一种新的基于操作员的行为评估方法进行评估。将对动物进行纵向评价，以研究年龄对8-27月龄雄性和雌性Fisher Hybrid（F344 BN）大鼠热敏感性的累积效应沿着感觉变化对体能的影响。由于慢性炎症是导致肌肉骨骼疼痛的常见疾病，是老年人残疾的主要原因，因此将努力研究年龄，慢性炎症和炎症损伤后自主神经功能变化之间的相互关系。还将评估生命早期慢性损伤对生命后期超敏反应发展的诱发影响。将通过检查脊髓小胶质细胞的年龄依赖性变化和背根神经节中的热受体表达，评价感觉功能年龄依赖性变化的潜在中枢与外周机制。拟议的研究代表：（a）迈向与年龄相关的疼痛分子和生理机制有关的机制研究的重要一步;及（B）将基本疼痛研究转化为与老年人疼痛障碍有关的临床策略的关键环节。为了实现这些目标，将使用由疼痛和行为，小胶质细胞，身体表现和统计分析专家组成的多学科团队来执行拟议的研究计划。拟议的研究代表了一种创新的方法，首次将纵向设计与临床相关的操作性行为评估策略相结合，以研究年龄对热敏感性的影响。公共卫生相关性：老年人的慢性疼痛在临床上、生物学上和治疗上比年轻人群的疼痛复杂得多，因此为旨在了解年龄对慢性疼痛发展和维持的影响的研究提供了理论基础和动机。拟议的研究代表：（a）迈向与年龄有关的疼痛行为、分子及生理机制的机制研究的重要一步;及（B）将基本疼痛研究转化为与老年人疼痛病症有关的临床试验策略的关键环节。

DESCRIPTION (provided by applicant): How advancing age impacts biological systems responsible for the experience of pain represents a major challenge in the field of pain research. Acknowledging the fact that chronic pain in the elderly is a far more complex condition clinically, biologically, and therapeutically than pain in younger segments of the population underscores the need for integrative studies encompassing behavioral changes and biological mechanisms responsible for alterations in pain perception with advancing age. Over the past 20 years knowledge related to peripheral and central substrates of pain has seen significant advances. Unfortunately, there is little evidence that anything we have learned applies to the pain system in the elderly (animals or humans). An examination of cellular and molecular mechanisms responsible for the development of chronic pain reveals an undeniable overlap with mechanisms responsible for aging, thus providing the rationale for studies evaluating the interaction between the biological process of aging and the pathological condition of chronic pain. Three specific aims related to the impact of advancing age on thermal sensitivity will be addressed, including efforts to define the temporal characteristics of age-related changes in heat and cold sensitivity. Thermal sensitivity will be evaluated with a novel operant-based method of behavioral assessment. Animals will be evaluated longitudinally to study the cumulative effects of age on thermal sensitivity along with the impact of sensory changes on physical performance in male and female Fisher Hybrid (F344BN) rats ranging in age from 8-27 months. Since chronic inflammation is a common condition contributing to musculoskeletal pain, a primary cause of disability in the elderly, efforts will be made to examine the interrelationships among age, chronic inflammation, and changes in autonomic function following inflammatory injury. The predisposing influence of chronic injury early in life to the development of hypersensitivity later in life will also be evaluated. Potential central versus peripheral mechanism(s) for age-dependent changes in sensory function will be evaluated by examining age-dependent changes in spinal microglia and thermal receptor expression in dorsal root ganglia. The proposed research represents: (a) an essential step towards mechanistic studies related to age- dependent molecular and physiological mechanisms of pain; and (b) a pivotal link for translating basic pain research into clinical strategies related to pain disorders in the elderly. To accomplish these objectives a multidisciplinary team consisting of experts in pain and behavior, microglia, physical performance, and statistical analysis will be used to carry out the proposed Research Plan. The proposed studies represent an innovative approach that for the first time combines a longitudinal design with a clinically relevant strategy of operant behavioral assessment to study the effects of age on thermal sensitivity. PUBLIC HEALTH RELEVANCE: Chronic pain in the elderly is a far more complex condition clinically, biologically, and therapeutically than pain in younger segments of the population thus providing the rationale and motivation for studies directed towards understanding the impact of age on the development and maintenance of chronic pain. The proposed research represents: (a) an essential step towards mechanistic studies related to age-dependent behavioral, molecular and physiological mechanisms of pain; and (b) a pivotal link for translating basic pain research into clinical trial strategies related to pain disorders in the elderly.