Dependence of histamine-evoked nociception on prostaglandin release.
Intraarterial injection of histamine into the isolated perfused rabbit ear causes a reflex fall in mean arterial blood pressure by stimulation of perivascular pain receptors. This effect is reduced by a low concentration of indomethacin (1 microgram/ml). The histamine H1-receptor antagonist mepyramine (10 micrograms/ml) reduced the effect of histamine. However, it also reduced the effect of acetylcholine. The histamine H2-receptor antagonist cimetidine (3-10 micrograms/ml) did not reduce the effect of histamine. Exogenously applied phospholipase A2 did not stimulate pain receptors on its own but enhanced the algesic effect of histamine, acetylcholine or bradykinin. This enhancement was abolished by indomethacin. Prostacyclin also enhanced the effect of histamine. The results suggest that histamine releases prostaglandins (E-type and prostacyclin) which in turn render the 'pain receptors' more sensitive to histamine. This effect may be of importance in inflammatory pain in that the effect of algogens (including histamine) is enhanced by an increased phospholipase A2-mediated synthesis of prostaglandins. Not only endogenously activated phospholipase A2 is able to split off prostaglandin precursors followed by subsequent generation of prostaglandins but also exogenously administered phospholipase A2 is able to induce the release of pain-enhancing prostaglandins.
D000818:Animals; D004347:Drug Interactions; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D054467:Phospholipases A2; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits; D012018:Reflex / Q000187:drug effects
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011453:Prostaglandins; D006632:Histamine; D010741:Phospholipases A; D054467:Phospholipases A2; D007213:Indomethacin