This year In the United States, """"""""baby boomers"""""""" are beginning to turn 60 years old at the rate of nearly 8000 people per day. The proportion of the US population aged >65 years is projected to increase from 12.4% in 2000 to 19.6% in 2030; this represents an increase from 35 million to an estimated 71 million persons. Chronic pain is 1) common among community-dwelling older persons with prevalence estimates that range from 15 to 50%, 2) is associated with declining physical performance and functional dependence, and 3) when treated, attenuates declining performance and slows the progression toward disability. Given that growing numbers of older persons are seeking treatment for chronic pain from primary care physicians, and that chronic use of opioids (i.e. """"""""narcotic"""""""" pain relievers such as morphine and fentanyl) is becoming better accepted for the treatment of many chronic pain conditions, it is inevitable that the chronic use of opioids in older persons is going to increase. Unfortunately, little is known about the long-term consequences of chronic administration of opioids, especially in older persons. The present studies are an attempt to examine the effects of chronic fentanyl administration on behavioral, pharmacological, and physiological outcomes using a well-defined rodent model of aging. Experiments in this application assess the short and long-term consequences of fentanyl administration to rats of different ages (the range is equivalent to 30 to 80 years of age in humans). The effects of this treatment will be examined on a number of physical performance measures (swim speed, agility, balance), cognitive tasks (learning and memory), and operant behavior (goal-directed responding). In addition, physiological outcomes that are directly related to the pharmacological actions of fentanyl including changes to body temperature regulation, analgesia (pain relief), and the potential development of hyperalgesia (increase in pain sensitivity) will be compared across ages. Finally, a more exploratory aim will assess fentanyl's effects on a known contributor to declining physical performance, changes in body composition (i.e. redistribution of lean versus fat mass assessed using magnetic resonance imaging). These assessments will be made over four weeks of chronic drug administration and a subsequent month-long withdrawal period. These experiments will identify potential risks and consequences of chronic opioid administration that vary as a function of age, and have implications for the increasing use of chronic opioid treatment in older persons for the management of pain. This application is directly responsive to the objectives of the current PA and the strategic aims of NIDA (as well as the National Institute on Aging) in that it establishes a preclinical model that will have direct translational implications for the evaluation of the long-term consequences of opioid administration to declining physical and cognitive performance, allowing an assessment of the potential abuse- related problems associated with this treatment regimen in the context of age-related pain. Opioids (narcotic pain relievers) are being used more for the treatment of pain although little is known about the consequences of chronic administration of these drugs, especially in older persons. Using rodents is necessary because study of the long-term effects of pharmacological treatment in humans would require several years of follow up, whereas initial testing in rats requires only months due to their compressed life spans. These experiments will identify potential health effects and long-term medical and behavioral consequences of chronic opioid administration that vary as a function of age, and have implications for the increasing use of chronic opioid treatment in older persons for the management of pain. ? ? ?
| Mitzelfelt, Jeremiah D; Carter, Christy S; Morgan, Drake (2014) Thermal sensitivity across ages and during chronic fentanyl administration in rats. Psychopharmacology (Berl) 231:75-84 |
| Morgan, Drake; Mitzelfelt, Jeremiah D; Koerper, Lorraine M et al. (2012) Effects of morphine on thermal sensitivity in adult and aged rats. J Gerontol A Biol Sci Med Sci 67:705-13 |
| Mitzelfelt, Jeremiah D; Dupree, Jameson P; Seo, Dong-oh et al. (2011) Effects of chronic fentanyl administration on physical performance of aged rats. Exp Gerontol 46:65-72 |
| Yezierski, R P; King, C D; Morgan, D et al. (2010) Effects of age on thermal sensitivity in the rat. J Gerontol A Biol Sci Med Sci 65:353-62 |
| Morgan, Drake; Carter, Christy S; DuPree, Jameson P et al. (2008) Evaluation of prescription opioids using operant-based pain measures in rats. Exp Clin Psychopharmacol 16:367-75 |
