PMC

Low doses of cinnabarinic acid significantly reduced formalin-induced nocifensive response in wild-type (WT) mice. (A) Effect of lowest doses of cinnabarinic acid (0.125 and 0.25 mg/Kg) on formalin-induced pain behaviours, including lifting, flinching, and licking, observed for 60 min at 5 min intervals. (B) Total pain scores were classified as phase I (0–10 min) and phase II (30–60 min) in formalin-injected mice treated with vehicle or with cinnabarinic acid (0.125 and 0.25 mg/Kg). (C) Effect of highest doses of cinnabarinic acid (0.5 and 3 mg/Kg) on formalin-induced pain behaviours, including lifting, flinching, and licking, observed for 60 min at 5 min intervals. (D) Total pain scores were classified as phase I (0–10 min) and phase II (30–60 min) in formalin-injected mice treated with vehicle or with cinnabarinic acid (0.5 and 3 mg/Kg). Data are expressed as the means ± SEMs (two-way ANOVA for repeated measures with Tukey’s post-hoc test, *p < 0.05, **p < 0.01, and ****p < 0.0001 vs. vehicle, n = 6–8).

Cinnabarinic acid-induced analgesia was mediated by the activation of mGlu4 receptor in WT and mGlu4^–/– mice. (A) Effect of cinnabarinic acid (0.25 mg/Kg) alone or in combination with CH223191 (1 mg/Kg) on formalin-induced pain behaviours, including lifting, flinching, and licking, observed for 60 min at 5 min intervals. (B) Total pain scores were classified as phase I (0–10 min) and phase II (30–60 min) in formalin-injected mice treated with vehicle or with cinnabarinic acid (0.25 mg/Kg) alone or in combination with CH223191 (1 mg/Kg). (C) Effect of cinnabarinic acid (0.25 mg/Kg) on formalin-induced pain behaviours, in WT and in mGlu4^–/– mice, observed for 60 min at 5 min intervals. (D) Total pain scores were classified as phase I (0–10 min) and phase II (30–60 min) in WT and in mGlu4^–/– mice formalin-injected mice treated with vehicle or with cinnabarinic acid (0.25 mg/Kg). Data are expressed as the means ± SEMs (two-way ANOVA for repeated measures with Tukey’s post-hoc test, *p < 0.05 vs. vehicle, ^$$p < 0.01 vs. CH223191, and ^####p < 0.0001 vs. CA, n = 8–10).

Low doses of cinnabarinic acid (CA) correct MK-801-induced biochemical alterations in prefrontal cortex. (A) MK-801-evoked glutamate release in prefrontal cortex. Values are means ± S.E.M. (n = 7–8). *P < .05 (1-Way ANOVA for repeated measures + Fisher’s test) [F_(1,69) = 14.491]. (B) Immunoblot analysis of KCC2 in prefrontal cortex. Values are means ± S.E.M. (n = 4–6). P < .05 (1-way ANOVA + Fisher’s test vs saline + saline [*] or saline + MK-801 [#]) [F_(2,11) = 16.586].

Structure of cinnabarinic acid and xanthurenic acid.