FIGURE 8.
Peptidomimetic PAR2 agonists induce thermal hyperalgesia in vivo. Thermal hyperalgesia was assessed in male ICR mice using the method of Hargreaves et al. (21). After establishing a baseline thermal latency, the latency to paw withdrawal was measured for 180 min following injection of vehicle or 3, 10, or 30 μg of 2-f-LIGRLO-NH2 (A) or 2-at-LIGRL-NH2 (C). Both 2-f-LIGRLO-NH2 and 2-at-LIGRL-NH2 induced thermal hyperalgesia for up to 90 min postinjection with the peak response occurring at a dose of 30 μg. The area under the curve for each dose of 2-f-LIGRLO-NH2 (B) and 2-at-LIGRL-NH2 (D) is plotted, and significance was determined using a one-way analysis of variance analysis (n = 6 for all conditions). Both PAR2 agonists were potent activators of hyperalgesia. To examine the specificity of each agonist in vivo, the latency to paw withdrawal was measured in PAR2−/− and wild-type control mice (PAR2+/+) for 90 min following injection of 30 μg of 2-f-LIGRLO-NH2 (E) or 2-at-LIGRL-NH2 (F). PAR2 expression was required for thermal hyperalgesia response with either PAR2 agonist. BL, base line. Significant differences from baseline are indicated: *, p < 0.05; **, p < 0.01; ***, p < 0.001.
