Nitric oxide evokes pain in humans on intracutaneous injection

To test the hypothesis that nitric oxide (NO) acts algetically in humans, we determined pain intensity/dose relations for intracutaneously applied NO solutions. NO, dissolved in isoosmolar phosphate buffer, was injected in the forearm of six volunteers and the subjects rated NO-evoked pain continuously with the help of an electronically controlled visual analogue scale. Pain always occurred at a NO dose of 12 nmol, increased with dose and reached the tolerance maximum at 50 nmol. This shows for the first time the genuine pain evoking properties of NO.