Effects of neonatal spinal cord serotonin depletion on opiate-induced analgesia in tests of thermal and mechanical pain.
There is considerable evidence that serotonin (5-HT) is involved in the analgesic actions of various opiates. However, it is less clear which opioid receptor types interact with these descending systems and whether the various monoaminergic pathways are specific for different types of nociceptive signals. In the present study we lesioned the spinal cord serotonin pathways by neonatal spinal injections of 5,7-dihydroxytryptamine (5,7-DHT) and tested the analgesic effects of morphine and ketocyclazocine one and two weeks later using both mechanical and thermal noxious stimuli. The treatment depleted spinal cord serotonin by more than 90% while not affecting norepinephrine levels. The effects of morphine were greatly attenuated in the depleted animals when the thermal noxious stimulus was applied. The analgesic actions of morphine were only slightly affected when the mechanical stimulus was applied. The effects of ketocyclazocine were not reduced by the treatment. The results further buttress the conclusion that at least part of morphine's analgesic effects are mediated by descending serotonin systems and that these systems are primarily effective against a thermal stimulus. The data suggest that non-5-HT brainstem system(s) are involved in morphine-induced analgesia to a mechanical noxious stimulus.
Giordano
J
J
Department of Neurotoxicology, Johns Hopkins School of Hygiene, Baltimore, MD.
Barr
G A
GA
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D000831:Animals, Newborn; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D016314:Ethylketocyclazocine / Q000031:analogs & derivatives*; D006358:Hot Temperature; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D004102:Dihydroxytryptamines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D016314:Ethylketocyclazocine; C012395:ketazocine; D009020:Morphine; D003496:Cyclazocine; D003891:Desipramine