r-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids氟比洛芬酯减少在啮齿动物通过恢复内源性大麻类神经性疼痛.pdfVIP

R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids 1. 1. 1 ¨ 1 1 Philipp Bishay , Helmut Schmidt , Claudiu Marian , Annett Haussler , Nina Wijnvoord , Simone Ziebell1, Julia Metzner 1, Marco Koch3¤, Thekla Myrczek 1, Ingo Bechmann2¤, Rohini Kuner4, Michael Costigan5, Faramarz Dehghani3¤, Gerd Geisslinger1, Irmgard Tegeder 1* 1 pharmazentrum frankfurt/ZAFES, Clinical Pharmacology, Goethe-University, Frankfurt, Germany, 2 Department of Clinical Neuroanatomy, Institute of Anatomy, Goethe- University, Frankfurt, Germany, 3 Department of Experimental Neurobiology, Institute of Anatomy, Goethe-University, Frankfurt, Germany, 4 Department of Pharmacology, University of Heidelberg, Heidelberg, Germany, 5 Neuroplasticity Research Group, Department of Anaesthesia, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America Abstract Background: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. Methodology/Principal Findings: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcri