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  • Title: Platelet-activating factor antagonists decrease the inflammatory nociceptive response in rats.
    Author: Teather LA, Magnusson JE, Wurtman RJ.
    Journal: Psychopharmacology (Berl); 2002 Oct; 163(3-4):430-3. PubMed ID: 12373444.
    Abstract:
    RATIONALE: Platelet-activating factor (PAF) is a membrane-derived phospholipid mediator that has biological effects on a variety of cells and tissues. A variety of stimuli, including those producing inflammation, promote the synthesis and release of PAF from various cell types. Evidence suggests that PAF exerts cellular actions through a plasma membrane receptor as well as via intracellular (microsomal) PAF binding sites. OBJECTIVE: The present study was designed to: 1) investigate the role of PAF in a model of inflammatory nociception in rats (i.e. the formalin test), and 2) localize PAF's site(s) of action in nociception. To do this, we assessed the effect of administering two PAF antagonists (BN 52021 and BN 50730, which are selective for cell surface and intracellular PAF binding sites, respectively) on formalin-induced nociceptive responses. METHODS: Forty minutes prior to formalin injection into the rat hindpaw, male Sprague-Dawley rats received systemic injections of BN 52021 (10, 1, or 0.1 mg/kg), BN 50730 (10, 1, or 0.1 mg/kg), or vehicle (45% 2-hydroxypropyl-beta-cyclodextrin in distilled water, HBC) and the effects of the drugs on nociceptive behavioral responses were measured. RESULTS: Rats receiving systemic BN 52021 or BN 50730 displayed a significant reduction of nociceptive responses in the late, but not early, phase of formalin-induced nociception. CONCLUSIONS: These findings suggest a role for endogenous PAF in nociceptive transmission, especially for persistent pain such as that which occurs in the late phase of the formalin test. The findings also indicate that both intracellular and cell surface PAF binding sites are involved in nociceptive modulation in rats, and that PAF antagonists might be useful for treating some patients with acute or chronic pain.
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