Fig. 3: Inhibition of CAP-induced TRPV1 currents and calcium responses in small- to medium-sized mouse DRG neurons following pretreatment with exendin 9–39, an antagonist of GLP-1, and its analgesic effects on CAP-induced nociceptive behaviors in mice. | Experimental & Molecular Medicine

Fig. 3: Inhibition of CAP-induced TRPV1 currents and calcium responses in small- to medium-sized mouse DRG neurons following pretreatment with exendin 9–39, an antagonist of GLP-1, and its analgesic effects on CAP-induced nociceptive behaviors in mice.

From: GLP-1 and its derived peptides mediate pain relief through direct TRPV1 inhibition without affecting thermoregulation

Fig. 3

a Effects of intraplantar administration of exendin 9–39 (Exe 9–39) (10 μg) on heat sensitivity via the Hargreaves test. Two-way ANOVA followed by the Bonferroni multiple comparison test (*p < 0.05, compared with the saline group). b Representative inward currents induced by 100 nM CAP in the presence of 100 nM exendin 9–39 (Exe 9–39; left). Mean normalized currents of sequential CAP-induced currents (mean ± S.E.M.; right). Two-tailed unpaired t test (****p < 0.0001, compared with each control CAP). c Representative traces of calcium influx elicited by 100 nM control CAP and pretreatment with 100 nM Exe 9–39. The calcium response to high potassium (KCl, 50 mM) was used to identify neurons (left). Mean normalized 340/380 ratios of sequential CAP-induced calcium increases (mean ± S.E.M.; right). Two-tailed unpaired t test (****p < 0.0001, compared with each control CAP). d Effects of intraplantar administration of exendin 9–39 (5 and 10 μg) and BCTC (0.5 μg) on CAP (1.6 μg)-induced acute licking time (mean ± S.E.M., n = 5). One-way ANOVA followed by Dunnett’s multiple comparison test (#p < 0.05, ####p < 0.0001, compared with the vehicle + CAP group). e Effects of the intraperitoneal administration of exendin 9–39 (50 mg/kg) or BCTC (5 mg/kg) on body temperature (mean ± S.E.M., n = 5). Two-way ANOVA followed by the Bonferroni multiple comparison test (*p < 0.05, ****p < 0.0001, vehicle group compared with the BCTC group; †††p < 0.001, ††††p < 0.0001, exendin 9–39 compared with the BCTC group). f Effects of intraplantar administration of exendin 9–39 (5 and 10 μg) on CAP-induced acute thermal hyperalgesia (left) and mechanical allodynia (right) in mice (mean ± S.E.M., n = 5 each). Two-way ANOVA followed by the Bonferroni multiple comparison test (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, compared with the vehicle group; #p < 0.05, ##p < 0.01, ###p < 0.001, ####p < 0.0001, compared with the vehicle + CAP group). ANOVA analysis of variance, CAP capsaicin, DRG dorsal root ganglia, GLP-1 glucagon-like peptide-1, S.E.M. standard error of the mean, TRPV1 transient receptor potential vanilloid 1.

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