Studies in the primate on the analgetic effects associated with intrathecal actions of opiates, alpha-adrenergic agonists and baclofen.
The effects of intrathecally administered opiates (morphine sulfate and meperidine), alpha-adrenergic agonists (clonidine and ST-91) and baclofen were examined on the shock titration threshold of macaque monkeys chronically prepared with intrathecal (I) or epidural (E) catheters. Spinal opiates produced a long-lasting analgesia which was antagonized by naloxone. The order of potency was I morphine greater than I meperidine greater than E meperidine greater than E morphine. Clonidine and ST-91, also produced a dose-dependent, long-lasting elevation in the shock titration threshold, antagonized by phentolamine, but not naloxone. L-baclofen, but not D-baclofen, resulted in a dose-dependent elevation of shock titration threshold, which was not antagonized by naloxone. Repeated administration at 24-h intervals over a 7-day period of morphine, clonidine or baclofen, resulted in a significant reduction in the analgetic effects of each drug. Cross tolerance between the three classes of agents was not observed. Intrathecal co-administration of inactive doses of ST-91 and morphine resulted in a near maximal increase in the shock titration threshold, which failed to show any significant tolerance over 21 days. Intrathecal ST-91 and morphine produced no change in either muscle strength, tendon reflexes, respiratory rate, urine formation, or the ability to locomote. Baclofen, in contrast, produced a dose-dependent decrease in muscle strength. That the intrathecal drugs did not produce anesthesia was demonstrated by their failure to block the avoidance response to ensuing ear shock cued by a light tactile stimulus applied to the hind paw. These results clearly indicate that a powerful analgesia can be produced by selectively activating adrenergic, opiate, and baclofenergic receptor systems in the spinal cord.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001418:Baclofen / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004597:Electroshock; D005260:Female; D007278:Injections, Spinal; D008251:Macaca; D008253:Macaca mulatta; D008297:Male; D008614:Meperidine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology; D010646:Phentolamine / Q000494:pharmacology; D012684:Sensory Thresholds; D013116:Spinal Cord / Q000187:drug effects / Q000648:ultrastructure
D000316:Adrenergic alpha-Agonists; D009294:Narcotics; D009270:Naloxone; C011266:ST 91; D009020:Morphine; D008614:Meperidine; D001418:Baclofen; D003000:Clonidine; D010646:Phentolamine