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. Author manuscript; available in PMC: 2020 Jan 1.
Published in final edited form as: Pain. 2019 Jan;160(1):160–171. doi: 10.1097/j.pain.0000000000001387

Figure 1.

Figure 1.

Intraplantar administration of methylglyoxal produces nociceptive responses: involvement of TRPA1 channels and nascent protein synthesis. (A) Intraplantar (i.p.) administration of MGO produces dose-dependent acute flinching behavior. One-way ANOVA: F(3, 20) = 10.22, P = 0.003; post-hoc Dunnett: ***P < 0.001, vehicle vs MGO (7.2 ng). Unpaired t test: t = 3.012; *P = 0.0131, vehicle vs MGO (720 ng). n = 6. (B) A low dose of MGO (0.2-7.2 ng/25 μL i.p.) induces a short-term mechanical hypersensitivity. Two-way ANOVA: F(12, 80) = 5.62, P < 0.001. Post-hoc Tukey; vehicle vs MGO (2 ng) at 1 hour: **P = 0.018, at 3 hours: ***P = 0.003, at 1 day: *P = 0.0398. vehicle vs MGO (7.2 ng) at 1 hour, 3 hours, 1 day: ****P = 0.0001. n = 6. (C) A high dose of MGO (720 ng/25 μL i.p.) produces long-lasting mechanical hypersensitivity. Two-way ANOVA: F(6, 60) = 8.163, P < 0.0001. Post-hoc Bonferroni; vehicle vs MGO (720 ng)at 1 hour, 3 hours, 1 day, and 6 days: ****P < 0.0001, at 15 days: ***P = 0.002. n = 6. (D) Methylglyoxal-induced short-term mechanical hypersensitivity is not blocked by A967079 (30 μg, i.p.), a TRPA1 channel antagonist. (E) A967079 (30 μg, i.p.) produced a minor antinociceptive effect after a high dose of MGO (720 ng/25 μL, i.p.). (F) Anisomycin (25 μg, i.p.), a nascent protein synthesis inhibitor, attenuates mechanical hypersensitivity produced by a low dose of MGO. Two-way ANOVA: F(5,132) = 3.343, P = 0.0071. Post-hoc Bonferroni; MGO + vehicle vs MGO + anisomycin at 1 hour: ****P = 0.0003, at 3 hours: **P = 0.0035. n = 12. (G) Mechanical hypersensitivity produced the high dose of MGO is prevented by anisomycin (25 μg, i.p.). Two-way ANOVA: F(6, 79) = 2.513, P = 0.0281. Post-hoc Bonferroni; MGO + vehicle vs MGO + anisomycin at 3 days: **P = 0.0035. (H) Coadministration of A967079 (30 μg, i.p.) and anisomycin (25 μg, i.p.) completely blocks the mechanical hypersensitivity produced by the high dose of MGO. Two-way ANOVA: F(7,70) = 3.866, P = 0.0013. Post-hoc Bonferroni; MGO + vehicle vs MGO + A967079 + Anisomycin at 1 hour: ****P = 0.0001, at 3 hours: *** P = 0.0004, at 6 hours: ***P = 0.0003, at 1 days: **P = 0.0038, at 3 days: ***P = 0.002, at 6 days: ****P < 0.0001, and at 12 days: *0.0254. n 5 6. ANOVA, analysis of variance.