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 occurring algetic and a potent NO liberator, evoke pain from hand veins. The afferent innervation of these veins consists solely of polymodal nociceptors which are located close to the endothelium, a well-known source of NO, thus suggesting NO as a chemical link in nociception. Consistent 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-synthase (NOS) inhibitor NG-mono-methyl-L-arginine. An intact NOS pathway is therefore a prerequisite for pain to be evoked by bradykinin and hyperosmolar solutions from veins, indicating for the first time in humans that vascular pain is mediated by NO. Thus, new directions for research on analgesics may be opened.