Presidents Corner

Does Getting Older Really Hurt?
Effects of Age on Pain Sensitivity
Robert P. Yezierski, Ph.D
Comprehensive Center for Pain Research
 University of Florida, Gainesville, Florida

It is well documented that sensory capacities decline as a function of advancing age. Sensitivity decreases for hearing, taste, smell, touch and vision, due in part to a diminished number of specialized peripheral receptors and deterioration of supporting tissues. Consistent with other sensory modalities, numerous age-related anatomical, chemical and functional changes have been documented in the somatosensory system. In addition to peripheral changes, altered expression of neurotransmitters and specialized pain receptors are observed in the spinal cords of old animals and human post mortem material. Furthermore the aging dorsal horn, especially lamina I, exhibits changes suggesting degeneration of descending modulatory circuits, including decreased levels of serotonin and norepinephrine. Such changes could decrease inhibitory influences and enhance activation of spinal neurons by peripheral input. Thus, numerous age-related changes within peripheral and central somatosensory pathways could create a predisposition to increased or decreased pain sensitivity (Gagliese and Farrell, 2005).

The above description of age-related changes in neural substrates of somatosensation underscores how advancing age impacts biological systems responsible for the sensory experience of pain. In recent years significant progress has been made in addressing the effects of age on pain perception but there remains a growing need for improved understanding of the biopsychosocial changes responsible for the complexity of pain in the elderly. At the outset it is important to acknowledge that chronic pain in the elderly is a far more complex condition clinically, biologically, and therapeutically than pain in younger segments of the population (Gibson and Weiner, 2005). How the biological changes associated with aging integrate with a lifelong history of physical and psychosocial events represents a large part of the challenge associated with achieving an understanding of the relationship between advancing age and the pain experience.

Over the past 20 years there have been significant advances in our understanding of the molecular biology, anatomy, physiology, pharmacology, and genetics of pain. Coupled with an increased understanding of the psychosocial contribution to the pain experience, there now exists a wealth of new information that provides a foundation for the development of novel strategies for the treatment of chronic pain. Unfortunately, little evidence exists regarding the relevance of anything we have learned to the aging somatosensory system. When one considers the effects of age on neuronal survival and the changing functional state of neurons, it is important to understand that these age related biological processes may have a significant impact on the overall pain experience.

Understanding the biological process of aging and the impact on the perception of nociceptive information requires development of animal models and behavioral strategies to monitor changing sensibilities across the life span of experimental animals. In recent years animal studies examining the effects of age on pain sensitivity have resulted in conflicting observations, including increases, decreases or no change in cutaneous sensibilities with advancing age (Gagliese and Farrell, 2005; Gagliese and Melzack, 2000). The behavioral approach used in the majority of these studies employ reflex-based behavioral measures of nociceptive sensitivity which unfortunately do not appropriately reveal the effects of experimental treatments known to affect pain sensitivity of humans. In a recent study a novel strategy of operant escape along with reflex tests were used to evaluate the impact of age on thermal sensitivity under normal conditions and during chronic inflammation following formalin injections in the dorsal hindpaws (Yezierski et al., 2010). Operant measures of pain assessment revealed an increased thermal sensitivity across the life span of the rat, but reflex responding was not similarly affected by age. Furthermore, inflammation induced by formalin injections increased thermal sensitivity significantly more in older animals than their younger counterparts. These results may offer some insight into why our neighbors to the north migrate to Florida in the winter months and why we have such a large retirement population in the state.

 
Although significant progress has been made in understanding the neurobiology of pain and aging, as we move forward there remains many important questions related to the effects of age on the pain experience including effects on: (a) intrinsic modulatory systems; (b) efficacy of therapeutic agents; (c) predictors of chronic pain; (d) hormonal influences on pain sensitivity; (e) pain sensitivity between males and females; and (f) pain sensitivity as a function of exercise, stress, diet, and immune function. Development of pre-clinical models and translational research strategies to address these questions represent a significant challenge to the future success of developing novel strategies to managing chronic pain in the elderly.

References

1. Gagliese, L, Farrell, MJ (2005). The neurobiology of aging, nociception and pain: an integration of animal and human experimental evidence. In: Pain in Older Persons, IASP Press, Seattle, pp. 25-44.
2. Gagliese L and Melzack R (2000) Age differences in nociception and pain behavioral in the rat. Neuroscience and Biobehav. Rev. 24:843-854.
3. Gibson, SJ and Weiner, DK (2005) Pain in Older Persons, Progress in Pain Res. and Management, Vol. 35, IASP Press, Seattle.
4. Yezierski, R.P., Carter, C.S., King, C.D., Morgan, D., Vierck, C.J, (2010) The effects of age on pain sensitivity. Journal of Gerontology: Biological Sciences (in press).