Effects of aging on spinal opioid-induced antinociception.
5)-; Aging/*physiology; Ala(2)-MePhe(4)-Gly(5)-; Analgesics; Animals; D-Penicillamine (2; delta/agonists; Dose-Response Relationship; Drug; Enkephalin; Enkephalins/administration & dosage/pharmacology; Hot Temperature; Inbred F344; Injections; Male; mu/agonists; Nociceptors/*drug effects; Opioid; Opioid/administration & dosage/*pharmacology; Pain Measurement/drug effects; Rats; Receptors; Spinal; Spinal Cord/*physiology
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.
Crisp T; Stafinsky J L; Hoskins D L; Dayal B; Chinrock K M; Uram M
Neurobiology of aging
1994
1994-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0197-4580(94)90108-2" target="_blank" rel="noreferrer noopener">10.1016/0197-4580(94)90108-2</a>
A lack of supersensitivity to opioid receptor agonists following chronic spinal opioid receptor antagonist administration in the rat.
5)-; Ala(2)-MePhe(4)-Gly(5)-; Animals; D-Penicillamine (2; Dose-Response Relationship; Drug; Enkephalin; Enkephalins/*pharmacology; Male; Naltrexone/analogs & derivatives/pharmacology; Narcotic Antagonists/*pharmacology; Opioid/*drug effects; Rats; Receptors; Somatostatin/analogs & derivatives/pharmacology; Species Specificity; Spinal Cord/*drug effects; Sprague-Dawley
1. Male Sprague-Dawley rats were chronically tested with intrathecal (i.t.) receptor selective opioid antagonists to determine if antinociceptive supersensitivity developed to selective i.t. opioid receptor agonists. 2. A subcutaneously implanted osmotic minipump was used to deliver the mu-opioid receptor antagonist CTOP (0.3 nmol) or the delta-opioid receptor antagonist naltrindole (5.5 nmol) for 7 days. 3. Following a 24 hr washout period, rats received a single i.t. dose (ED50) of either DAMPGO (for CTOP-treated animals) or DPDPE (for naltrindole-treated animals) and the antinociceptive effects of the agents were tested on the tail-flick test. 4. Our findings revealed that chronic spinal treatment with selective opioid receptor antagonists did not induce an antinociceptive supersensitivity to selective opioid receptor agonists. 5. Perhaps this lack of supersensitivity is reflective of difficulties inherent to opioid receptor antagonists that do not possess negative intrinsic activity.
Keck B J; Stafinsky J L; Uram M; Crisp T
General pharmacology
1995
1995-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0306-3623(94)00154-f" target="_blank" rel="noreferrer noopener">10.1016/0306-3623(94)00154-f</a>
Age-related changes in the spinal antinociceptive effects of DAGO, DPDPE and beta-endorphin in the rat.
Male; Animals; Rats; Analysis of Variance; Aging/*physiology; Injections; Analgesics/*pharmacology; Pain/*physiopathology; beta-Endorphin/administration & dosage/*pharmacology; Enkephalins/administration & dosage/*pharmacology; Spine/drug effects/growth & development/*physiology; Dose-Response Relationship; Drug; Enkephalin; Inbred F344; Ala(2)-MePhe(4)-Gly(5)-; Spinal; 5)-; D-Penicillamine (2
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; Stafinsky J L; Hoskins D L; Perni V C; Uram M; Gordon T L
Brain research
1994
1994-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
A comparative analysis of monoaminergic involvement in the spinal antinociceptive action of DAMPGO and DPDPE.
Male; Animals; Rats; Injections; Enkephalins/*pharmacology; Naloxone/pharmacology; Anesthetics/*pharmacology; Biogenic Monoamines/*physiology; Pain/*metabolism; Spinal Cord/drug effects/metabolism/*physiopathology; Dose-Response Relationship; Drug; Inbred Strains; Receptors; Enkephalin; Ala(2)-MePhe(4)-Gly(5)-; Spinal; 5)-; D-Penicillamine (2; Opioid/drug effects/*physiology; Enkephalins; Intraspinal; Amines – Physiology; Anesthetics – Pharmacodynamics; Cell Surface – Drug Effects; Cell Surface – Physiology; Enkephalins – Pharmacodynamics; Naloxone – Pharmacodynamics; Pain – Metabolism; Spinal Cord – Drug Effects; Spinal Cord – Metabolism; Spinal Cord – Physiopathology
The antinociceptive properties of intrathecally (i.t.) administered [D-Ala2,
Spanos L J; Stafinsky J L; Crisp T
Pain
1989
1989-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0304-3959(89)90046-8" target="_blank" rel="noreferrer noopener">10.1016/0304-3959(89)90046-8</a>