Inhibition of platelet-activating factor receptors in hippocampal plasma membranes attenuates the inflammatory nociceptive response in rats.
Evidence suggests that platelet-activating factor (PAF) is a mediator in inflammatory-based pain. Using the biphasic formalin model in rats, we recently demonstrated that PAF antagonists which were selective for either intracellular or plasma membrane PAF receptors decreased the late-phase of the nociceptive response. Inasmuch as both of the PAF antagonists previously used were administered systemically, and reportedly are able to cross the blood-brain barrier, the anatomic locations at which PAF affects pain processing remained to be elucidated. Since PAF is required for hippocampal-dependent memory consolidation, and since the hippocampus has been shown to mediate the late-phase of formalin-induced nociception, the present study investigated the effects on nociception of administration of PAF antagonists within the hippocampus, and of using agents specific for either plasma membrane (BN 52021) or intracellular (BN 50730) PAF binding sites. Intrahippocampal injections of BN 52021 decreased the late-phase of the nociceptive response in a concentration-dependent manner. In contrast, intrahippocampal administration of BN 50730 had no effect on inflammatory nociception. These findings suggest that hippocampal plasma membrane PAF receptors, but not intracellular PAF binding sites, mediate tonic inflammatory pain processing in rats.
Teather
Lisa A
LA
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. lteather@mit.edu
Afonso
Veronica M
VM
Wurtman
Richard J
RJ
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D004224:Diterpenes / Q000494:pharmacology; D046934:Ginkgolides; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010147:Pain Measurement / Q000379:methods*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000502:physiology
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C045856:ginkgolide B