Effects of aging on spinal opioid-induced antinociception.

Initial experiments were conducted to determine whether or not the aging process alters the ability of young, mature, or aged male Fischer 344 rats (5- to 6-, 15- to 16-, and 25- to 26-months-old, respectively) to respond to thermal nociceptive stimuli. Using the tail-flick analgesiometric assay, 25- to 26-month-old rats responded significantly faster to the heat source than 15- to 16-month-old animals, but no significant differences were noted between the 5- to 6-month-old and aged rats. Another series of investigations compared the effects of aging on the spinal antinociceptive properties of the mu opioid agonist [D-Ala2,N-methyl-Phe4,Gly5-ol] enkephalin (DAMPGO) and the delta agonist [D-Pen2,D-Pen5] enkephalin (DPDPE). In these studies, young, mature, and aged rats were injected intrathecally (IT) with different doses of DAMPGO or DPDPE, and opioid-induced antinociception was tested on the tail-flick test. All three age groups responded to IT DAMPGO in a dose-dependent manner but, for the most part, higher spinal doses were required to produce significant elevations in tail-flick latency in the aged cohort of rats. The spinal analgesic effects of DPDPE also declined with advanced age. The aging process apparently alters the pain-inhibitory function of mu and delta opioid receptors in the rat spinal cord.