Fig. 1
From: The industrial solvent 1,4-dioxane causes hyperalgesia by targeting capsaicin receptor TRPV1
1,4-Dioxane causes mice hyperalgesia via TRPV1 activation. a The radiant heat test shows 1,4-dioxane-caused thermal hyperalgesia in WT mice but not in Trpv1-/- mice. b Von Frey filament assay evaluating the effect of 1,4-dioxane on mechanical pain sensing. c Intraplantar injections of 10 μl of 5% 1,4-dioxane significantly increased paw volume compared with that injected with saline controls. The paw edema ratio is the percentage increase of paw volume induced by 1,4-dioxane in Trpv1+/+ mice. The effects of 1,4-dioxane were abolished in Trpv1-/- mice. The representative images of the dioxane-injected paw edema are shown on the left. d Responses of dorsal root ganglia (DRG) neurons acutely isolated from Trpv1+/+ or Trpv1-/- mice were consecutively challenged with 1 μM capsaicin (Cap), 5% 1,4-dioxane, and 60 mM KCl, as indicated. Channel activation was assessed by calcium imaging in cells loaded with the fluorescent Ca2+ indicator Fluo-4, AM. The colored bar indicates relative calcium levels. e Averaged responses of DRG neurons dissociated from Trpv1+/+ (gray, n = 61) or Trpv1-/- (red, n = 45) mice to capsaicin, 1,4-dioxane, and KCl. Fluo-4 epifluorescence changes were computed as (Fi–F0)/F0, where Fi represented fluorescence intensity at any frame and F0 was the baseline fluorescence calculated from the averaged fluorescence of the first 10 frames. f Percentage of DRG neurons responding to capsaicin (1 μM), 1,4-dioxane (5%), or high KCl (60 mM) in neurons isolated from Trpv1+/+ or Trpv1-/- mice. g Trigeminal ganglia (TG) neurons from Trpv1+/+ or Trpv1-/- mice were challenged with 1,4-dioxane (5%) followed by capsaicin (1 μM), then high KCl (60 mM). Quantification of responses were assessed by calcium imaging (n ≥ 30 cells per trace). h Percentage of TG neurons responding to capsaicin, 1,4-dioxane, or high KCl in neurons isolated from Trpv1+/+ or Trpv1-/- mice. i Typical response of DRG neurons cultured from wild-type (i1) and Trpv1-deficient (i2) mice to 1,4-dioxane and capsaicin. j Quantification of peak currents for recordings in (i1). k–l Similar recordings and statistical results in TG neurons. m Quantification of responses to 1,4-dioxane (5%) and capsaicin (5 μM) in both DRG and TG neurons cultured from wild-type or Trpv1-/- mice (n ≥ 8). Responses to 1,4-dioxane were observed only in the capsaicin sensitive neurons