The purpose of the present study was to examine the effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) on nociceptive thresholds in man. On two different study days twelve healthy subjects received a stair case infusion of GTN (0.015, 0.25, 1.0, 2.0 micrograms/kg/min 20 min each dose) or placebo in a randomized double-blind cross-over design. Before the infusion and after 15 min of infusion on each dose, pressure pain detection- and tolerance thresholds were determined by pressure algometry in three different anatomic regions (finger, a temporal region with interposed myofascial tissue and a temporal region without interposed myofascial tissue). Relative to placebo the three higher GTN doses induced a decrease in both detection- and tolerance-thresholds in the temporal region with interposed myofascial tissue. No such changes were observed in the two other stimulated regions. These results could reflect central facilitation of nociception by NO. However, convergence of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO may provide a more likely explanation.