discovery of prostamide f2α and its role in inflammatory pain and dorsal horn nociceptive neuron hyperexcitability发现prostamide f2α及其作用,炎症性疼痛和疼痛的背角神经元兴奋过度.pdfVIP

Discovery of Prostamide F2a and Its Role in Inflammatory Pain and Dorsal Horn Nociceptive Neuron Hyperexcitability 1. 2. 1 1 3 Luisa Gatta , Fabiana Piscitelli , Catia Giordano , Serena Boccella , Aron Lichtman , 1 2 Sabatino Maione *, Vincenzo Di Marzo * 1 Endocannabinoid Research Group, Department of Experimental Medicine–Division of Pharmacology ‘‘L. Donatelli’’, Second University of Naples, Naples, Italy, 2 Endocannabinoid Research Group, Institute of Biomolecular Chemistry, C.N.R., Pozzuoli, Italy, 3 Department of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, United States of America Abstract It was suggested that endocannabinoids are metabolized by cyclooxygenase (COX)-2 in the spinal cord of rats with kaolin/l- carrageenan-induced knee inflammation, and that this mechanism contributes to the analgesic effects of COX-2 inhibitors in this experimental model. We report the development of a specific method for the identification of endocannabinoid COX-2 metabolites, its application to measure the levels of these compounds in tissues, and the finding of prostamide F2a (PMF2a) in mice with knee inflammation. Whereas the levels of spinal endocannabinoids were not significantly altered by kaolin/l- carrageenan-induced knee inflammation, those of the COX-2 metabolite of AEA, PMF2a, were strongly elevated. The formation of PMF2a was reduced by indomethacin (a non-selective COX inhibitor), NS-398 (a selective COX-2 inhibitor) and SC-560 (a selective COX-1 inhibitor). In healthy mice, spinal application of PMF2a increased the firing of nociceptive (NS) neurons, and correspondingly reduced the thres