Fig. 3: TRPM8 allows recovery of normal sensitivity in male mice exposed to nitroglycerin or formalin. | Nature Communications

Fig. 3: TRPM8 allows recovery of normal sensitivity in male mice exposed to nitroglycerin or formalin.

From: TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

Fig. 3

a Wild-type and TRPM8 knockout males display similar acute mechanical hypersensitivity after nitroglycerin (left panel). Deletion of this receptor prevents recovery of baseline mechanical sensitivity after chronic nitroglycerin treatment in males (right). Acute and long-lasting hypersensitivity is similar in wild-type and knockout females. b Trigeminal TRPM8 mRNA expression is similar regardless of sex or nitroglycerin/vehicle treatment. c Calcium responses of trigeminal cultures from males and females chronically exposed to nitroglycerin or vehicle after exposure to TRPM8 agonist WS12 (500 nM). d Average size of calcium transients after WS12 is similar in neurons from males and females. Response sizes vs. respective KCl responses. e Female mice chronically exposed to nitroglycerin show increased mechanical sensitivity when compared to vehicle-treated mice. This sensitivity remained unchanged after 10 mg/kg WS12 i.p. f Nocifensive behavior in the acute phase of the formalin test (5 min) is significantly alleviated in females receiving 6 nmol WS12 i.pl. g TRPM8 antagonist AMTB (i.p.) unmasks latent mechanical pain sensitization in mice chronically exposed to nitroglycerin that already recovered their basal sensitivity. h 10 mg/kg AMTB administered 1 h after formalin injections induces significant reinstatement of licking behavior in males. Mean mechanical thresholds (a, e, g), expression (b), response size (d), nocifensive behavior (f, h) ± S.E.M. Datapoints without error bars represent values of individual animals. a ##p < 0.01 vs. baseline. ^^p < 0.01 vs. vehicle two-way RM ANOVA n = 5 mice per condition. b Two-way ANOVA n = 6 samples from six different mice per condition, obtained after one behavioral experiment. d Two-way ANOVA n = 5 samples from five different mice per condition, obtained after three independent experiments. e ***p < 0.001 nitroglycerin vs. vehicle, three-way ANOVA n = 6(Veh + Veh), n = 5(NTG + Veh), n = 6(Veh + WS12), n = 7(NTG + Veh WS12) mice. f *p < 0.05 vs. vehicle. Multiple two-sided t-test n = 4(WS12) or 7(Vehicle) mice. g +p < 0.05 vs. vehicle. Two-sided Friedman test n = 6 mice. h *p < 0.05 vs. vehicle. Multiple two-sided t-test n = 6 mice per condition. ORX orchidectomy, NTG nitroglycerin, Veh vehicle. Source data are provided in Source Data file, statistical results in Supplementary Table 3.

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