title: Pharmacological evidence for a role of lipoxygenase products in platelet-activating factor (PAF)-induced hyperalgesia.
abstract: Platelet-activating factor (PAF), a potent inflammatory mediator, decreases the nociceptive threshold in the rat hindpaw. Pain sensitivity, measured by the applied pressure necessary to induce vocalization, was increased maximally at 3 and 4 hr after injection of synthetic PAF. The hyperalgesic response to PAF was specifically inhibited by agents that interfere with the lipoxygenase pathway of arachidonic acid metabolism and was not affected by cyclooxygenase inhibitors. BW-755C (3-30 mg/kg, p.o.) and L-615,919 (0.01-0.3 mg/kg, p.o.) significantly reduced PAF-induced hyperalgesia, whereas indomethacin had no effect. The finding that L-615,919, a specific 5-lipoxygenase inhibitor, was a potent inhibitor of this model of hyperalgesia leads to speculation that leukotrienes are important mediators of inflammatory pain.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
authors.forename: A
authors.initials: A
authors.lastname: Dallob
authors.forename: Y
authors.initials: Y
authors.lastname: Guindon
authors.forename: M M
authors.initials: MM
authors.lastname: Goldenberg
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced*; D006941:Hyperesthesia / Q000139:chemically induced*; D007975:Leukotriene B4 / Q000494:pharmacology; D008084:Lipoxygenase / Q000502:physiology*; D010972:Platelet Activating Factor; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010972:Platelet Activating Factor; D007975:Leukotriene B4; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases