Figure 1.
Chemogenetic inhibition of TRPV1+ afferent terminals attenuates mechanical hyperalgesia and ongoing pain in mice with ION-CCI. A, Effects of CNO on mechanical hyperalgesia following ION-CCI in mice expressing inhibitory DREADD in TRPV1-LN neurons (TRPV1Cre;R26LSL-hM4Di; hM4Di) or TRPV1Cre mice (Cre). CNO was repeatedly injected intraperitoneally (40 µg/20 µl), to ipsilateral (ipsi; 20 µg/10 µl) or contralateral (contra; 20 µg/10 µl) V2 skin or intra-Vc (Vc; 0.1 µg/1 µl) at indicated time points. Mechanical sensitivity is presented as EF50 (the mechanical force that produced a 50% response frequency) in the ipsilateral V2 skin; *p < 0.05, **p < 0.01, ***p < 0.001 in Bonferroni post hoc test following two-way ANOVA. Throughout the figures, numbers in parenthesis represent the number of mice in each group. B, Preconditioning habituation started at four to five weeks after CCI or sham surgery. Following the habituation period, the mice received intra-Vc microinjection of vehicle (0.5-µl saline) in the ipsilateral side and paired with a chamber for 30 min. Four hours later, the same mouse received 0.5-µl CNO paired with the other conditioning chamber for 30 min. On the following test day, the mice were placed in the CPP chambers with free access to all chambers to measure time spent in both chambers. Mice were recorded for 15 min, and difference scores were calculated by subtracting time spent in CNO-paired chambers before conditioning from the time after conditioning; *p < 0.05, **p < 0.01 in Bonferroni post hoc test following two-way ANOVA. C, The effects of AMG9810 (100 nmol/10 µl), a TRPV1 antagonist, or vehicle injected into the ipsilateral V2 skin on mechanical sensitivity in the ipsilateral V2 skin of mice with ION-CCI.