The Journal of Neurophysiology Vol. 81 No. 3 March 1999, pp. 963-966
Copyright ©1999 by the American Physiological Society

NOS Inhibitor Antagonism of PGE₂-Induced Mechanical Sensitization of Cutaneous C-Fiber Nociceptors in the Rat

National Institutes of Health Pain Center and Departments of Anatomy, Medicine, and Oral and Maxillofacial Surgery, Division of Neuroscience, University of California, San Francisco, California 94143-0440

Chen, Xiaojie and Jon D. Levine. NOS inhibitor antagonism of PGE₂-induced mechanical sensitization of cutaneous C-fiber nociceptors in the rat. Prostaglandins, metabolites of arachidonic acid, released during tissue injury and inflammation sensitize primary afferent nociceptors. While it has been suggested that this effect on nociceptors is mediated mainly via the cAMP second messenger system, recent evidence suggests that nitric oxide (NO) is also involved in peripheral pain mechanisms. To test the hypothesis that NO contributes to the sensitization of nociceptors to mechanical stimuli induced by hyperalgesic prostaglandins, we compared von Frey hair mechanical threshold as well as the response evoked by 10-s sustained threshold mechanical stimulation before and after injection of prostaglandin E₂ (PGE₂) alone, and NOS inhibitor N^G-methyl-L-arginine (L-NMA) or its inactive stereoisomer N^G-methyl-D-arginine (D-NMA) plus PGE₂, adjacent to the receptive field of C-fiber nociceptors. The reduction of mechanical threshold and increase in number of action potentials to sustained mechanical stimulation induced by intradermal application of PGE₂ was blocked by L-NMA, but not D-NMA. It is suggested that NO contributes to nociceptor sensitization induced by hyperalgesic prostaglandins.