NITRIC-OXIDE EVOKES PAIN AT NOCICEPTORS OF THE PARAVASCULAR TISSUE AND VEINS IN HUMANS

1. Nitric oxide (NO) evokes pain on intracutaneous application, appare ntly by exciting cutaneous nociceptors. To look for similarities in th e responsiveness and sensitivity of other nociceptive systems to NO we determined pain intensity-concentration relations for NO applied to p aravascular tissue and veins in humans. 2. NO solutions (0.4-200 mM) w ere either injected paravascularly or perfused through a vascularly is olated hand vein segment. The subjects rated pain continuously with th e help of an electronically controlled visual analog scale, which made it possible to determine both the time course (latency, duration) and the intensity of NO-evoked pain. 3. Regardless of where it was applie d, at concentrations above 0.7 mM NO always evoked pain of similar tim e course and concentration dependence. Pain increased proportionally t o the concentration of applied NO, reaching subjects' tolerance maximu m at four to five times the threshold concentration. 4. Pain intensity -NO concentration relations were congruent, indicating that the respec tive nociceptive systems are equally sensitive to NO. 5. Our observati ons are consistent with the hypothesis that NO is a chemical link in p eripheral nociception.