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Age-related changes in the spinal antinociceptive effects of DAGO, DPDPE and beta-endorphin in the rat
T Crisp1, J L Stafinsky, D L Hoskins
1Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272-0095.
Abstract:
These studies were designed to investigate how the aging process alters the spinal antinociceptive efficacy of mu (mu), delta (delta) and epsilon (epsilon) opioid receptor agonists administered intrathecally (i.t.) in rats. Various doses of the mu agonist DAGO, the delta agonist DPDPE or the putative epsilon beta-endorphin were injected i.t. in young (5-6-month-old), mature (15-16-month-old) and aged (25-26-month-old) Fischer 344 rats. Antinociception was measured using the rat tail-flick analgesiometric assay. The data demonstrated a decline in spinal opioid-induced antinociception as a function of age. For instance, the i.t. dose of DPDPE or beta-endorphin needed to produce antinociception in the 25-26-month-old rats was higher than that needed to elevate tail-flick latency in the young and mature animals. We also noted that the i.t. doses of the opioid agonists needed to produce 'antinociception' in the aged cohort were within a range of spinal doses that produced motor impairment. Apparently, the aging process alters the ability of opioid receptors to mediate antinociception. Perhaps an age-related decrease in the number and/or affinity of opioid receptor sites in the rat spinal cord accounts for these observations.
Insights
Aging reduces the effectiveness of spinal opioid agonists for pain relief in rats. Higher doses are needed in older rats, potentially impacting motor function due to altered opioid receptor efficacy.
Area of Science:
- Neuroscience
- Pharmacology
- Gerontology
Background:
- Opioid receptors are crucial for pain modulation.
- The impact of aging on spinal opioid efficacy is not fully understood.
Purpose of the Study:
- To investigate age-related changes in spinal antinociception mediated by mu, delta, and epsilon opioid receptors.
- To determine if aging affects the efficacy of intrathecal opioid administration.
Main Methods:
- Intrathecal administration of mu (DAGO), delta (DPDPE), and epsilon (beta-endorphin) agonists in young, mature, and aged Fischer 344 rats.
- Assessment of antinociception using the rat tail-flick assay.
- Observation of motor function at tested doses.
Main Results:
- A significant decline in spinal opioid-induced antinociception was observed with advancing age.
- Older rats required higher intrathecal doses of DPDPE and beta-endorphin for antinociception compared to younger rats.
- Effective antinociceptive doses in aged rats overlapped with doses causing motor impairment.
Conclusions:
- The aging process impairs the spinal antinociceptive efficacy of mu, delta, and epsilon opioid receptor agonists.
- Age-related decreases in opioid receptor number and/or affinity in the spinal cord may underlie these findings.
- These results suggest altered pain management strategies may be needed for elderly individuals.