Endogenous serotonin (5-HT) and norepinephrine (NE) comprise the descending pain-inhibitory system, which modulates spinal nociceptive input. Monoamine oxidase (MAO) metabolizes endogenous 5-HT and NE, and recent studies have demonstrated that MAO activity in the brain increases with age. The present experiments are designed to investigate age-related differences in the perception of pain and spinal opiate- induced antinociception in young,mature and aged rats. Initial studies will investigate the effects of aging on the perception of thermally- mediated nociceptive stimuli in 6, 16 and 26 month old male Fischer 344 rats. Nociceptive will be measured using the tail-flick and hot plate analgesiometric assays.
In Specific Aim#2, a neurochemical analysis will be made of the spinal levels of 5-HT, NE, dopamine and their respective metabolites in cervical, thoracic, and lumber and sacral spinal cord segments of 6, 16 and 26 month old rats. The neurochemical studies will be conducted using HPLC coupled with electrochemical detection. The studies comprising Specific Aim #3 will investigate age-related changes in the spinal antinociceptive efficacy of DAMPGO (a m agonist), DPDPE (a delta agonist) and Beta-endorphin (an epsilon opioid receptor agonist) in young, mature and aged rats. The tail-flick and hot plate analgesiometric tests will be used to measure opiate-induced spinal analgesia. Lastly, Specific Aim #4 will assess age-related differences in the role of spinal mu, delta and epsilon opioid receptor subtypes in the spinal antinociceptive effects of DAMPGO, DPDPE and Beta-endorphin. In these studies, 6, 16 and 26 month old rats will receive i.t. pretreatments with a receptor-selective mu, delta or epsilon opiate antagonist (CTP-NH2, naltrindole or Beta-endorphin 1-27, respectively) prior to a fixed antinociceptive dose of i.t. DAMPGO, DPDPE or Beta- endorphin. The inhibitory efficacy of each receptor antagonist against each opiate agonist will be determined in young, mature and aged rats, and ID50 values will be generated. These studies will further identify the relevant opioid receptor subtype(s) in the spinal cord responsible for mediating opiate-induced antinociceptive as a function of age.
| Hoskins, D L; Gordon, T L; Crisp, T (1998) The effects of aging on mu and delta opioid receptors in the spinal cord of Fischer-344 rats. Brain Res 791:299-302 |
| Sunanda; Rao, B S; Raju, T R (1998) Corticosterone attenuates zinc-induced neurotoxicity in primary hippocampal cultures. Brain Res 791:295-8 |
| Crisp, T; Stafinsky, J L; Hoskins, D L et al. (1994) Effects of aging on spinal opioid-induced antinociception. Neurobiol Aging 15:169-74 |
| Crisp, T; Stafinsky, J L; Hoskins, D L et al. (1994) Age-related changes in the spinal antinociceptive effects of DAGO, DPDPE and beta-endorphin in the rat. Brain Res 643:282-6 |
