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. 2019 May 31;9(15):4287–4307. doi: 10.7150/thno.36077

Figure 2.

Figure 2

The roles of Nav1.7, mast cells, and histamine in MGO-induced itch in mice. (A) MGO (3 μmol)-induced scratching was significantly decreased in RTX-treated mice (n = 5 for each group, ***P < 0.001 compared with VEH group, Student's t test). (B) Co-administration of pan sodium channels blocker TTX (100 ng) significantly reduced MGO (3 μmol)-induced scratching in mice. (n = 6-8 for each group, **P < 0.01 compared with VEH group, Student's t test). (C) Nav1.7 selective inhibitor PF-05089771 (10 μg) significantly reduced MGO (3 μmol)-induced scratching in mice (n = 6-7 for each group, *P < 0.05 compared with VEH group, Student's t test). (D) Nav1.8 selective inhibitor A803467 (3 μg) did not affect MGO (3 μmol)-induced scratching in mice (n = 6 for each group, P > 0.05 compared with VEH group, Student's t test). (E) Pan T-type calcium channel inhibitor Mib (10 nmol) did not affect MGO (3 μmol)-induced scratching in mice (n = 5 for each group, P > 0.05 compared with VEH group, Student's t test). (F) MGO (3 μmol)-induced scratching behavior was significantly decreased in compound 48/80-pretreated mice (n = 5 for each group, ***P < 0.001 compared with NS group, Student's t test). (G-H) I.p. injection of a histamine H1 antagonist chlorpheniramine (1 and 10 mg/kg) dose-dependently suppressed MGO (3 μmol)-induced scratching behavior (G; n = 5 for each group, **P < 0.01; ***P < 0.001 compared with NS group, one-way AVOVA followed by post-hoc Dunnett's test), but did not affect CQ (200 μg)-induced scratching behavior in mice (H; n = 6-7 for each group, P > 0.05 compared with NS group, Student's t test). (I-J) I.p. injection of MGO (I; 50 mg/kg) and i.t. injection of MGO (J; 1 nmol) significantly increased MGO (3 μmol)-induced scratching in mice (n = 5 for each group, ***P < 0.001, *P < 0.05 compared with NS group, Student's t test). All data are expressed by means ± SEM. 48/80, compound 48/80; CQ, chloroquine; Mib, mibefradil; MGO, methylglyoxal; NS, normal saline; RTX, resiniferatoxin; TTX, tetrodotoxin; VEH, Vehicle.