Age-related changes in the spinal antinociceptive effects of DAGO, DPDPE and beta-endorphin in the rat.
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.
Crisp
T
T
Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272-0095.
Stafinsky
J L
JL
Hoskins
D L
DL
Perni
V C
VC
Uram
M
M
Gordon
T L
TL
D000375:Aging / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D013131:Spine / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001615:beta-Endorphin; D020881:Enkephalin, D-Penicillamine (2,5)-