Fig. 4

Activation of TRPV1 under inflammation-related conditions. a Effects of acid on the 1,4-dioxane-induced response in TRPV1-expressing HEK293 cells. Representative current traces evoked by varied concentrations of 1,4-dioxane in combination with the neutral pH (7.4) and then switched to pH 6.0. Acid strongly potentiated 1,4-dioxane responses at 0.3%, 0.5%, and 1% concentration. b The average plot compares the 1,4-dioxane response in pH 7.4 and 6.0 conditions. Currents were normalized to the responses evoked by 1 μM capsaicin. c A representative whole-cell recording of the TRPV1 E600Q mutant. The cell was exposed to different concentrations of 1,4-dioxane in neutral condition (pH 7.4). d Average plot of peak currents. The constitutively acidified TRPV1 E600Q mutant potentiated 1,4-dioxane-evoked current responses. e Potentiation of 1,4-dioxane (2%) responses by PDBu treatment in primary cultured DRG neurons. The phosphorylation of the channel induced by PDBu (2 μM) was verified with two capsaicin concentrations, 0.2 and 1 μM, applied before and after treatment. After phosphorylation, 1,4-dioxane (2%) or capsaicin (0.2 μM) elicited larger responses. The pipette solution also contained 2 mM MgATP. f Relative changes of the 1,4-dioxane- and capsaicin-evoked responses before and after phosphorylation. All recordings were made at a membrane potential of −60 mV. g The PWL of hind paws to radiant heat were measured for Trpv1^+/+ and Trpv1^-/- mice under carrageenan-induced inflammation conditions (left). Von Frey filament assay evaluating the effect of 1,4-dioxane on mechanical pain sensing under carrageenan-induced inflammation conditions (right)