Studies in the primate on the analgetic effects associated with intrathecal actions of opiates, alpha-adrenergic agonists and baclofen

Anesthesiology. 1981 Jun;54(6):451-67. doi: 10.1097/00000542-198106000-00004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Analgesia*
  • Animals
  • Avoidance Learning / drug effects
  • Baclofen / pharmacology*
  • Behavior, Animal / drug effects
  • Cats
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Drug Interactions
  • Electroshock
  • Female
  • Injections, Spinal
  • Macaca
  • Macaca mulatta
  • Male
  • Meperidine / pharmacology
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Narcotics / pharmacology*
  • Pain / physiopathology
  • Phentolamine / pharmacology
  • Sensory Thresholds
  • Spinal Cord / drug effects
  • Spinal Cord / ultrastructure

Substances

  • Adrenergic alpha-Agonists
  • Narcotics
  • Naloxone
  • ST 91
  • Morphine
  • Meperidine
  • Baclofen
  • Clonidine
  • Phentolamine