Age-related decrements in morphine analgesia: a parametric analysis.

Although age-related reductions in levels of opiate receptors and endogenous opioid peptides have been observed in rats, effects of aging upon basal pain thresholds and morphine analgesia have not indicated clear results. The present study evaluated the dose-dependent (1,2.5, 5 and 10 mg/kg, SC) and time-dependent (30, 60, 90, 180 min) properties of morphine analgesia on two nociceptive measures (tail-flick latencies and jump thresholds) across five age cohorts of rats (4, 9, 14, 19 and 24-months of age). To ascertain whether any changes were the result of specific alterations in pain inhibition or an overall shift in opiate responses, effects upon morphine-induced hyperthermia were also evaluated. Age-related effects upon morphine analgesia on the tail-flick test exhibited a biphasic pattern with the three older age groups displaying significant decreases in morphine analgesia 30 min after injection and significant increases in morphine analgesia 180 min after injection. Age-related effects upon morphine analgesia on the jump test revealed equivilent reductions in analgesic magnitude across doses for the three older cohorts. In contrast, morphine hyperthermia displayed small inconsistent changes across cohorts. The reductions in morphine analgesia in older animals could not be attributed to changes in either baseline pain thresholds or delayed peripheral absorption and/or clearance of the drug. Rather, the reductions in morphine analgesia in older animals complement the recent findings of similar age-related reductions in the analgesic responses induced by exposure to several environmental stressors.