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. 2011 Apr 5;286(21):19076–19088. doi: 10.1074/jbc.M110.185264

FIGURE 8.

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.