Opioid-monoamine interactions in spinal antinociception: evidence for serotonin but not norepinephrine reciprocity.
Anatomical and electrophysiological studies have demonstrated that enkephalinergic, noradrenergic, and serotonergic pathways projecting from the brain-stem to the dorsal horn inhibit nociceptive transmission at the spinal level. Previous attempts to delineate interactions between opioids, norepinephrine (NE), and serotonin (5-HT) in the production of spinal analgesia have produced conflicting results. The present study determined the effect of intrathecal (i.t.) pretreatment with opioid, NE, and 5-HT antagonists upon i.t. monoamine- and morphine-induced antinociception as assessed with the rat tail-flick model. Naloxone, at a dose which antagonized i.t. morphine analgesia, had no effect upon i.t. NE but inhibited i.t. 5-HT antinociception. Corynanthine or yohimbine (NE antagonists) reduced analgesia elicited by i.t. NE but not morphine, while pretreatment with methysergide or ketanserin (5-HT antagonists) attenuated both i.t. 5-HT- and morphine-induced antinociception. These results suggest that (1) an opioid link mediates spinal 5-HT but not NE antinociception, and (2) 5-HT but not NE participates in spinal morphine analgesia.
Kellstein
David E
DE
Department of Pharmacology and Toxicology, Philadelphia College of Pharmacy and Science, Woodland Avenue at 43rd Street, Philadelphia, PA 19104 U.S.A.
Malseed
Roger T
RT
Goldstein
Frederick J
FJ
D000698:Analgesia; D000818:Animals; D004723:Endorphins / Q000502:physiology*; D008297:Male; D009020:Morphine; D009638:Norepinephrine / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D009435:Synaptic Transmission
D004723:Endorphins; D012701:Serotonin; D009020:Morphine; D009638:Norepinephrine