Figure 5.

Hyperalgesic agents that also induce priming when injected into the paw produce hyperalgesia, but not priming, when injected in the DRG. A–C, Groups of rats received intraganglion (i.gl.) injection of the hyperalgesic mediators ψεRACK (10 μg; A), NGF (1 μg; B), or TNF-α (10 μg; C). The mechanical threshold was evaluated 60 min and 24 h later. A–C, The paws ipsilateral to the DRGs that received injection of these mediators showed significant mechanical hyperalgesia when compared with the control paws (ipsilateral to the DRGs treated with vehicles; A, **p < 0.01; B, ***p < 0.001, **p < 0.01; C, p < 0.001, when the change in mechanical threshold induced by the i.gl. priming inducers or control is compared over 24 h; two-way repeated-measures ANOVA followed by Bonferroni post-test). One week later, when the mechanical thresholds were not significantly (NS) different from the baseline nociceptive thresholds evaluated before the injection of the mediators (A: ψεRACK group, t₍₅₎ = 0.8402, p = 0.4391; control group, t₍₅₎ = 1.164, p = 0.2968; B: NGF group, t₍₅₎ = 0.9543, p = 0.3837; control group, t₍₅₎ = 0.4740, p = 0.6554; C: TNF-α group, t₍₅₎ = 0.7559, p = 0.4838; control group, t₍₅₎ = 0.9764, p = 0.3737; paired Student's t test), PGE₂ (100 ng) was injected intradermally into the dorsum of the hindpaw, and mechanical hyperalgesia was evaluated 30 min and 4 h later. Average paw-withdrawal thresholds before the injection of the mediators and before the injection of PGE₂ (1 week later) were as follows: 123.0 ± 2.3 and 119.0 ± 2.7 g, respectively, for the ψεRACK-treated group, and 117.6 ± 1.8 and 115.0 ± 1.0 g, for the control-treated group; 118.6 ± 1.8 and 116.3 ± 1.7 g, respectively, for the NGF-treated group, and 117.6 ± 2.9 and 119.0 ± 1.9 g, for the control-treated group; and 118.3 ± 1.8 and 121.0 ± 2.5 g, respectively, for the TNF-α-treated group; and 117.3 ± 2.1 and 119.6 ± 2.0 g, for the control-treated group. Evaluation of the mechanical hyperalgesia induced by PGE₂ showed significant hyperalgesia at 30 min after injection, which was no longer present at the fourth hour time point, in all groups. Two-way repeated-measures ANOVA followed by Bonferroni post-test showed no difference between the controls and the groups treated with the mediators (NS), indicating that i.gl. injection of ψεRACK, NGF, or TNF-α did not produce hyperalgesic priming (N = 6 paws per group).