Department of Orthodontics, Comprehensive Center for Pain Research, University of Florida, Gainesville, Florida 32610, USA.
Pain Med. 2012 Apr;13 Suppl 2(Suppl 2):S27-36. doi: 10.1111/j.1526-4637.2011.01311.x.
Preclinical studies of pain and aging represent an area of research where considerations of age, strain, gender, and method of behavioral assessment are but some of the challenges that must be addressed. The results of studies related to the impact of age on pain sensitivity have ranged from increased to decreased sensitivity to no change. Examining the design of these studies one discovers that cross-sectional designs using animals of different ages have been used to evaluate age-related effects in normal animals as well as animals with inflammatory and neuropathic pain conditions. In the present review a summary of these studies is presented along with a discussion of potential mechanisms responsible for changes that have been described.
The dominant method of behavioral assessment in the majority of studies involving rodents has been reflex-based strategies that unfortunately do not reveal the same effects of experimental manipulations known to affect pain sensitivity in humans. A comparison of results obtained with reflex-based methods versus those obtained with cortically dependent operant methods reveals significant differences.
Increases in pain sensitivity under different experimental conditions have been suggested to result from age-related anatomical, physiological, and biochemical changes as well as compensatory changes in homeostatic mechanisms and intrinsic plasticity of somatosensory pathways involved in the processing and perception of pain. Other factors that may contribute to the impact of age on pain sensitivity include dysregulation of the hypothalamic-pituitary-adrenal axis and changes in autonomic function that occur with advancing age. In the future translational research in the field of pain and aging will need to focus on establishing clinically relevant animal models and assessment strategies to evaluate the causal relationships between the biological changes associated with advancing age and the varied behavioral changes in pain sensitivity.
疼痛和衰老的临床前研究是一个研究领域，其中必须考虑年龄、品系、性别和行为评估方法等因素。与年龄对疼痛敏感性的影响相关的研究结果从敏感性增加到敏感性降低到没有变化不等。研究这些研究的设计，就会发现使用不同年龄的动物进行横断面设计，已被用于评估正常动物以及患有炎症性和神经性疼痛疾病的动物的年龄相关影响。在本综述中，总结了这些研究，并讨论了描述的变化的潜在机制。
在涉及啮齿动物的大多数研究中，行为评估的主要方法是基于反射的策略，但不幸的是，这些方法并未揭示出与已知影响人类疼痛敏感性的实验操作相同的效果。基于反射的方法与基于皮质的操作性方法获得的结果进行比较，显示出明显的差异。
在不同的实验条件下，疼痛敏感性增加被认为是由于与年龄相关的解剖、生理和生化变化以及涉及疼痛处理和感知的躯体感觉通路的内稳态机制和固有可塑性的代偿性变化所致。可能导致年龄对疼痛敏感性的影响的其他因素包括下丘脑-垂体-肾上腺轴的失调以及随着年龄的增长而发生的自主功能变化。在未来的疼痛和衰老领域的转化研究中，需要重点建立临床相关的动物模型和评估策略，以评估与年龄相关的生物学变化与疼痛敏感性的各种行为变化之间的因果关系。
