Fig. 1. GTN-induced delayed onset mechanical hyperalgesia.
(A). Nitroglycerin (GTN) was administered intradermally (0.1 ng, i.d.) on the dorsum of the hind paw. Mechanical nociceptive threshold was measured using the Randall-Selitto analgesymeter every 5 min for 120 min post GTN administration. GTN produced a decrease in nociceptive threshold, beginning ~30 min post-injection in males and ~45 min in females that remained undiminished for the duration of the testing period. During the plateau phase (30–120 min post administration), GTN-induced hyperalgesia was significantly greater in females (unpaired Student’s t-test, P<0.039)
(B). GTN was administered intravenously (4 µg/kg/min for 20 min) and mechanical nociceptive threshold evaluated at multiple time points between 30 and 440 min after starting GTN infusion. GTN produced a decrease in nociceptive threshold, beginning ~65 min after starting infusion in males but not until ~320 min in females. There is a significant difference in the effect of GTN in males and females (two-way repeated ANOVA, P<0.0001).