Figure 4: Intragastric exemestane (EXE) induces TRPA1-dependent prolonged mechanical allodynia and reduction in forelimb grip strength in mice.
In C57BL/6 mice intragastric (i.g.) administration of EXE (10 mg kg−1) induces (a) mechanical allodynia and (c) a reduction in forelimb grip strength that last 3–6 h after administration. EXE does not produce any acute nocifensor behaviour as measured by the indicated test (a, inset). (b,d) Three hours after EXE administration, HC-030031 (HC; 100 mg kg−1 i.p.) reverts both mechanical allodynia and the reduction in forelimb grip strength. HC inhibition is no longer visible 3 h after its administration. Veh is the vehicle of EXE. #P<0.05 versus Veh; Student’s t-test (a,c) and §P<0.05 versus Veh and *P<0.05 versus Veh HC-EXE; ANOVA followed by Bonferroni post hoc test (b,d). (e,f) EXE (once a day for 15 consecutive days, 10 mg kg−1 i.g.) induces reproducible mechanical allodynia and decrease in forelimb grip strength at day 1, 5, 10 and 15 in Trpa1+/+mice. Arrows indicate Veh or EXE administration. Both these effects are markedly reduced in Trpa1−/− mice. §P<0.05 versus Veh-Trpa1+/+, *P<0.05 versus EXE-Trpa1+/+; ANOVA followed by Bonferroni post hoc test. Results are mean±s.e.m. of at least five mice for each group. In all conditions, baseline (BL) levels were recorded 30 min before EXE administration.
