Fig. 3. AMP-, but not CPA-, induced mechanical hyperalgesia in female primed rats is dependent on estrogen receptor alpha (EsRα).

A: Male (left panel) and female (right panel) rats received an intradermal injection of ryanodine (100 ng in males and 1 pg in females) on the dorsum of both hind paws. One week later, intrathecal treatment with ODN antisense or mismatch against EsRα mRNA was performed for 3 consecutive days. On the 4^th day, AMP (1 μg) was injected at the same site as ryanodine, and mechanical nociceptive threshold evaluated 10, 20 and 30 min later. While AMP induced significant hyperalgesia in both male and female rats treated with mismatch and in the male antisense group, in the group of females that had been treated with EsRα antisense, AMP-induced hyperalgesia was prevented [males: F_1,10 = 1.179, p = 0.3030 (non-significant); females: F_1,10 = 52.35, ****p < 0.0001, when the antisense and mismatch groups are compared, two-way repeated measures ANOVA followed by the Bonferroni post-hoc test] indicating a dependence on EsRα for the hyperalgesic effect of AMP in female, but not in male, primed rats; B: Female rats that had been primed with an intradermal injection of ryanodine (1 pg) on the dorsum of both hind paws, were treated, one week later, with intrathecal injections of ODN antisense or mismatch against EsRα mRNA for 3 consecutive days. On the 4^th day, CPA (1 μg) was injected at the same site as ryanodine, and mechanical nociceptive thresholds were then evaluated 10, 20 and 30 min later. No difference in the hyperalgesia induced by CPA was observed between the antisense and mismatch groups [F_1,10 = 1.700, p = 0.2215 (non-significant), when the antisense and mismatch groups are compared, two-way repeated measures ANOVA followed by the Bonferroni post-hoc test]. (N = 6 paws per group)