INVOLVEMENT OF THE NO CYCLIC GMP PATHWAY IN BRADYKININ-EVOKED PAIN FROM VEINS IN HUMANS/

Cyclic GMP is probably a second messenger in vascular nociceptors that are excited by nitric oxide (NO), because NO is known to activate the guanylate cyclase. If so, inhibition of this enzyme should render noc iceptors insensitive to algesics that act via NO. To test this hypothe sis, the effect of the specific guanylate cyclase inhibitor methylene blue was studied on bradykinin-evoked, i.e. NO-mediated pain and, for control, on mechanically-evoked pain, which is probably not mediated b y NO. In eight subjects, pain was evoked from isolated hand vein segme nts by either injection of bradykinin (1 x 10(-6) M) or noxious balloo n distention. Pretreatment of the vein segments with methylene blue in hibited bradykinin-evoked pain in a concentration-dependent manner and abolished pain at a concentration of 1 x 10(-3) M. Methylene blue had no effect on mechanically evoked pain. Tachyphylaxis to intravenously applied bradykinin was not observed. These results are consistent wit h the hypothesis that cyclic GMP plays a role in the transduction of N O-mediated noxious stimuli in vascular nociceptors in humans.