Noradrenergic and purinergic involvement in spinal antinociception by 5-hydroxytryptamine and 2-methyl-5-hydroxytryptamine.
The adrenergic involvement in spinal antinociception by 5-hydroxytryptamine (5-HT) and 2-methyl-5-hydroxytryptamine (2-Me-5-HT) was examined using the alpha-adrenoceptor antagonists phentolamine, yohimbine and prazosin, and the neurotoxin 6-hydroxydopamine. Intrathecal pretreatment with phentolamine and yohimbine (7.5-30 micrograms), but not prazosin (30 micrograms), reduced the action of 5-HT and 2-Me-5-HT in both the tail flick and hot plate tests. Pretreatment with 6-hydroxydopamine (100 micrograms) reduced (5-HT) or increased (2-Me-5-HT) antinociception in the hot plate test, while tail flick responses were largely unaffected. In other experiments, 8-phenyltheophylline, an adenosine receptor antagonist, reduced the action of 5-HT, but not 2-Me-5-HT, in both tests. These results indicate that (a) antinociception by both 5-HT and 2-Me-5-HT involves some form of interaction with spinal alpha 2-adrenoceptors, but the nature of the interaction for these two agents is different because only 5-HT is dependent on endogenous noradrenaline, (b) release of adenosine from the spinal cord contributes to spinal antinociception by 5-HT but not by 2-Me-5-HT.
Sawynok
J
J
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Reid
A
A
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D058914:Purinergic Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000700:Analgesics; D058914:Purinergic Antagonists; D011942:Receptors, Adrenergic, alpha; D011983:Receptors, Purinergic; D015016:Yohimbine; D012701:Serotonin; C045918:2-methyl-5-HT; D016627:Oxidopamine; D013806:Theophylline; C028322:8-phenyltheophylline; D011224:Prazosin; D010646:Phentolamine