NITRIC-OXIDE AS A CHEMICAL LINK IN THE GENERATION OF PAIN FROM VEINS IN HUMANS

In humans, both nitric oxide (NO) and bradykinin, a naturally occurrin g algetic and a potent NO liberator, evoke pain from hand veins. The a fferent innervation of these veins consists solely of polymodal nocice ptors which are located close to the endothelium, a well-known source of NO, thus suggesting NO as a chemical link in nociception. Consisten t with this hypothesis, our observations show that neither bradykinin, nor hyperosmolar solutions (a noxious physicochemical stimulus) evoke pain from hand vein segments that have been exposed to the NO-synthas e (NOS) inhibitor N-G-mono-methyl-L-arginine. An intact NOS pathway is therefore a prerequisite for pain to be evoked by bradykinin and hype rosmolar solutions from veins, indicating for the first time in humans that vascular pain is mediated by NO. Thus, new directions for resear ch on analgesics may be opened.