Effects of L-menthol on acute acrolein-induced pain and CFA-induced mechanical hyperalgesia in wild-type, Trpm8−/−, or TRPM8 antagonist-treated mice
(A) Nocifensive behavior in wild-type (black) or Trpm8−/− (blue) mice quantified over 10 min following hindpaw injection of vehicle (Veh, PBS), acrolein alone (Acrol, 25 nmol in 50 μl PBS) or acrolein plus L-menthol (50 nmol, co-injected). n=9–10 mice per group. **p < 0.01, NS: not significant (p > 0.05).
(B) Effects of L-menthol on CFA-induced mechanical hyperalgesia in wild-type mice, measured by von Frey hair analysis. Baseline thresholds were measured before CFA injection (day 0). On days 1–3, mice were injected into the plantar surface of the paw with L-menthol (Ment, 60 nmol in 20 μl, green) or vehicle (PBS, red) 30 min prior to testing. Non CFA-treated mice are shown for comparison (black). n=7–8 mice per group. *p < 0.05 vs. CFA+Veh, ##p < 0.01 vs. Control, NS: not significant from CFA+Veh.
(C) Effect of TRPM8 antagonists, AMG2850, on L-menthol inhibition of CFA-induced mechanical hyperalgesia in wild-type mice. Experiment performed as in (B). AMG2850 was administered (30 mg/kg, i.p.) 45 min before von Frey test. L-menthol was injected into hindpaw 15 min later. n=7–8 mice per group.
(D) Effects of L-menthol on CFA-induced mechanical hyperalgesia in Trpm8−/− mice. Experiment performed as in (B) except that Trpm8−/− mice were used. n=7–8 mice per group.