Histaminergic mechanisms in clonidine induced analgesia in rat tail-flick test.
The role of neural histamine in clonidine-analgesia and in clonidine-induced potentiation of stress analgesia was studied. Pretreatment of rats with alpha-fluoromethylhistidine (FMH) (200 ug icv/rat; daily for five days) increased the analgesic effect of the alpha 2-agonist clonidine on the spinal reflex of the tail-flick test. Rats subjected to cold-restraint stress (30 min at 4 degrees C) showed increased latency compared to the unstressed rats. The analgesic efficacy of clonidine was significantly greater in rats subjected to cold-restraint with respect to unstressed rats. However, the inhibition of histamine biosynthesis by FMH significantly reduced cold-restraint analgesia in saline-controls, and consistently increased the analgesic efficacy of the alpha 2-agonist, showing a maximum latency. Yohimbine exhibited high affinity as an antagonist for alpha 2-receptors, inducing hyperalgesic effects and antagonizing clonidine analgesia and clonidine-induced potentiation of cold stress analgesia. In FMH-pretreated rats, yohimbine failed to reverse clonidine analgesia and did not block the increased analgesic efficacy of clonidine in cold-restrained FMH-pretreated rats. Results of this study suggest that inhibition of histamine release through alpha 2-adrenoceptors on histaminergic axons may contribute to the analgesic efficacy of systemically injected clonidine, also confirming that neural histaminergic pathways are implicated in the mediation of pain response in particular conditions of stress.
Arrigo-Reina
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R
Institute of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Catania, Italy.
Chiechio
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S
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003080:Cold Temperature; D006632:Histamine / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology; D015016:Yohimbine / Q000494:pharmacology
D000700:Analgesics; D008762:Methylhistidines; D015016:Yohimbine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase; D003000:Clonidine