Nicotine-Induced Analgesia In the tail immersion test, baseline measures revealed an effect of Sex (F(1, 110) = 17.0, p < .001), with females having lower nociceptive thresholds than males, independent of genotype (Figure 4A). Deletion of the ��4 subunit, however, did not affect basal thermal pain sensitivity, with no main effect sellckchem of Genotype and no interaction between Sex and Genotype. Nicotine had a dose-dependent antinociceptive effect in both males (Figure 4B) and females (Figure 4C). A three-way repeated-measures ANOVA revealed a significant effect of Sex (F(1, 110) = 40.9, p < .001), consistent with the sex difference in basal nociception. None of the two- or three-way interactions between Sex and the other factors were significant. Data from each sex were analyzed separately using two-way repeated-measures ANOVAs.

There was a significant main effect of Nicotine in both sexes (males: F(1, 43) = 17.3, p < .001, Figure 4B; females: F(1, 67) = 13.5, p < .001, Figure 4C). A main effect of Genotype (males: F(4, 172) = 48.9, p < .001; females: F(4, 268) = 86.0, p < .001) and a significant interaction between Nicotine and Genotype (males: F(4, 172) = 11.8, p < .001; females: F(4, 268) =10.0, p < .001) were also detected in males and females, indicating that nicotine-induced analgesia was reduced in ��4?/? mice (Figure 4B�CC). Figure 4. (A) Basal nociceptive thresholds in the tail immersion test. Tail withdrawal latencies (mean �� S E M) were measured in na?ve male and female ��4+/+ (black bars) and ��4?/? (white bars) mice. The numbers of ...

A similar pattern of results emerged in the hot plate test (Figure 5). Nicotine increased the latencies to display the first nocifensive response to noxious heat (males, Figure 5A; females, Figure 5D), hindpaw licking or flinching (males, Figure 5B; females, Figure 5E), and jumping (males, Figure 5C; females, Figure 5F). Three-way ANOVAs revealed a significant effect of Sex for all responses (first sign: F(1, 102) = 16.5, p < .001; hindpaw sign: F(1, 102) = 5.2, p < .05; jumping: F(1, 102) = 4.7, p < .05), with females having longer latencies than males. None of the two- or three-way interactions between Sex and the other factors were significant, with the exception of the Sex �� Nicotine interaction for jumping (F(2, 102) = 5.7, p < .05), which reflected the higher sensitivity of females to the antinociceptive effect of nicotine for that sign.

Data from each sex were then analyzed separately using two-way ANOVAs. There was a significant effect of Nicotine on the latency to display first sign (males: F(2, 39) = 15.3, p < .001, Figure 5A; females: F(2, 63) = 52.9, p < .001, Figure 5D), hindpaw sign (males: F(2, 39) = 10.7, p < .001, Figure 5B; females: F(2, 63) = 13.8, GSK-3 p < .001, Figure 5E), and jumping (males: F(2, 39) = 3.9, p = .056, Figure 5C; females: F(2, 63) = 48.0, p < .001, Figure 5F).