The Effects of Age on Pain Sensitivity: Preclinical Studies

Abstract

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.