Reversal of spinal cord non-opiate analgesia by conditioned anti-analgesia in the rat.
The spinal cord contains endogenous substances (such as cholecystokinin, FMRFamide, etc.) that can block the analgesic effects of opiates. Anti-opiate actions have been most commonly studied by exogenous administration of receptor agonists and receptor antagonists of these substances. However, we have recently demonstrated that anti-analgesia can be brought under environmental control through Pavlovian conditioning. Whereas analgesia can be conditioned to signals for danger, anti-analgesia can be conditioned to signals for safety. Using this paradigm, we have previously demonstrated that conditioned anti-analgesia can reverse a variety of opiate analgesic states, including those produced by conditioned danger signals, systemic morphine, and intrathecal mu- and delta-opiate receptor agonists. These data raise the question of the generality of anti-analgesia actions. The present series of experiments examined the ability of conditioned anti-analgesia to affect non-opiate analgesic states induced by spinal delivery of GABA(A), GABA(B), 5HT2 + 5HT1, and 5HT3 receptor agonists. While conditioned anti-analgesia had no effect on GABA(A) or 5HT2 + 5HT1 non-opiate analgesias, conditioned anti-analgesia completely blocked GABA(B) and 5HT3 non-opiate analgesias. These findings clearly demonstrate that conditioned anti-analgesia can powerfully modulate non-opiate as well as opiate analgesias and bring into question whether putative anti-opiate neuroactive substances may have broader actions than previously suggested.
Watkins
L R
LR
Department of Psychology, University of Colorado at Boulder, 80309, USA. lwatkins@clipr.colorado.edu
McGorry
M
M
Schwartz
B
B
Sisk
D
D
Wiertelak
E P
EP
Maier
S F
SF
D015360:Analgesia, Epidural; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D003214:Conditioning, Classical; D004353:Drug Evaluation, Preclinical; D018755:GABA Agonists / Q000494:pharmacology; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects*
D018712:Analgesics, Non-Narcotic; D001645:Biguanides; D018755:GABA Agonists; D007539:Isonicotinic Acids; D009292:Narcotic Antagonists; D017366:Serotonin Receptor Agonists; D009271:Naltrexone; D001418:Baclofen; C008846:phenyl biguanide; C015300:isoguvacine