Figure 1.

Ryanodine-induced priming is IP₃ receptor dependent. The IP₃ receptor antagonist xestospongin C (0.2 μg, black bars) was injected intradermally on the dorsum of the hindpaw of male (left) and female (right) rats; control groups (white bars) received vehicle. After 10 min, the doses of ryanodine previously shown to induce priming (100 ng in males and 1 pg in females) were injected at the same site. One week later, evaluation for the presence of priming was performed by intradermal injection of PGE₂ (100 ng) at the same site as ryanodine. Two-way repeated-measures ANOVA, followed by Bonferroni post hoc test, showed a significant attenuation of the hyperalgesia induced by PGE₂ at the fourth hour, in groups that had been pretreated with xestospongin C, compared with the control groups, pretreated with vehicle (males: F_(1,5) = 130.6; ***p < 0.0001; females: F_(1,5) = 89.10; ****p = 0.0002, when the hyperalgesia in the vehicle- and xestospongin C-treated groups is compared at the fourth hour), demonstrating that the induction of priming by ryanodine is dependent on the activation of IP₃ receptors (N = 6 paws per group).