Fig. 5.

RAGE agonism and antagonism modulate capsaicin-evoked intracellular Ca²⁺ changes in DRG neurons. (A) FPSZM1 had no effect on capsaicin-evoked TRPV1 activity at any concentration in 10 mM glucose conditions (n=4 per treatment). (B) FPSZM1 significantly reduced the capsaicin-evoked TRPV1 activity in 50 mM glucose conditions in a concentration-dependent manner (n=4 per treatment). (C) The high-glucose-induced increase in TRPV1 activity was completely prevented when neurons were co-treated with 10 nM FPSZM1 [n=4, 10 mM glucose and 50 mM glucose+FPSZM1; n=5, 50 mM glucose; one way ANOVA F(2,10)=8.398, P=0.0072. *P<0.05, **P<0.01 post-hoc Sidak's test]. (D) HMGB1 increased the capsaicin-evoked TRPV1 activity in a concentration-dependent manner [one-way ANOVA F(95,30)=2.688, P=0.04. *P<0.05 post-hoc Bonferroni tests compared with control, n=6 per treatment]. (E) The HMGB1-mediated (10 nM) increase in capsaicin-evoked TRPV1 activity was blocked by 10 nM FPSZM1 [n=4 per treatment, one-way ANOVA F(2,9)=42.63, P<0.0001]. Data are mean±s.e.m. and individual data points as shown. *P<0.05, **P<0.01 post-hoc Sidak's tests.