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. 2018 Feb 19;37(8):e97349. doi: 10.15252/embj.201797349

Figure 2. Pharmacological decrease in cholesterol enhances excitability of DRG neurons and causes hyperalgesia.

Figure 2

  • A
    Quantification of cholesterol content from skin paw biopsies of mice injected with MβCD (n = 6) or cholesterol oxidase (ChOxi; n = 8).
  • B
    Intraplantar injection of MβCD (n = 8), but not MβCD‐chol (n = 9), αCD (n = 7), or saline solution (n = 7), caused mechanical hypersensitivity. Effects of MβCD were not prevented by ibuprofen (75 mg/kg) injected intraperitoneally 1 h prior to intraplantar injection of MβCD (MβCD + ibu; n = 9).
  • C
    Intraplantar injection of MβCD (n = 8), but not αCD (n = 8) or saline solution (n = 8), caused heat hypersensitivity (Hargreaves radiant heat test).
  • D
    Development of mechanical hypersensitivity induced by intraplantar injection of ChOxi (n = 6).
  • E
    Cholesterol quantification in DRG cultures treated for 15 min with the saline (control, n = 7; MβCD, n = 9; or ChOxi, n = 7).
  • F
    Current threshold ratio for each DRG neuron was calculated by dividing the current threshold measured 12 min after drug treatment by that measured at t = 0 min (control, n = 7; MβCD, n = 7; ChOxi, n = 6; MβCD‐chol n = 5).
  • G
    Representative illustrations of current threshold in DRG neurons before (t = 0) and 12 min after bath application of MβCD and MβCD‐chol. Current steps were applied with 25‐pA increments. For clarity's sake, not all traces were illustrated. The red traces represent the voltage response induced by the injected current necessary to induce an action potential at t = 12 min. The dashed lines indicate 0 mV.
  • H, I
    Representative firing behavior of small DRG neurons before and after 12‐min treatment with MβCD (H) and ChOxi (I).
Data information: All values are shown as mean ± standard error of the mean (SEM). Cholesterol quantification (E) and current threshold (F) were analyzed with a non‐parametric Mann–Whitney U‐test. Behavioral data were analyzed with two‐way ANOVA and Bonferroni post‐tests. ***< 0.001, **< 0.01, and *< 0.05 (versus saline curve for B and C).