Figure 3.

Hyperalgesic priming can be detected at the spinal cord when it is induced at the hindpaw. Rats received intradermal injection of the PKCε activator ψεRACK (1 μg, black bars) into the dorsum of the right hindpaw. Vehicle (white bars) was injected into the left paw. Four days later, PGE₂ (20 ng/μl, 20 μl) was injected into the spinal cord, and the mechanical nociceptive paw withdrawal thresholds evaluated, 30 min and 4 h after PGE₂ injection. Average paw withdrawal thresholds before the injection of ψεRACK or vehicle and immediately before the intrathecal injection of PGE₂ (4 d later) were as follows: 119.1 ± 1.2 and 117.5 ± 1.2 g, respectively, for the vehicle group (t₍₁₁₎ = 1.101; p = 0.2945, NS); 119.6 ± 1.8 and 119.5 ± 1.3 g, respectively, for the ψεRACK group (t₍₁₁₎ = 0.1121; p = 0.9127, NS); paired Student's t test showed no significant difference between these two values. We observed a statistically significant increase in the magnitude of the hyperalgesia induced by the injection of PGE₂ in the paws previously treated with ψεRACK when compared with the vehicle-treated paws [30 min after PGE₂: **p < 0.01; 4 h after PGE₂: ***p < 0.001; two-way repeated-measures ANOVA followed by Bonferroni post-test, N = 6 rats (12 paws) per group], showing the presence of hyperalgesic priming (F_(1,22) = 35.20, p < 0.0001, when comparing both groups). The schematic on the left shows the signal triggered by the injection of ψεRACK (1, red syringe) at the peripheral terminal of the nociceptor in the skin, directed to the cell body (red arrow), and the signal from the cell body to the central terminal (blue arrow), where the presence of hyperalgesic priming can be detected by evaluating the hyperalgesia evoked by intrathecal injection of PGE₂ (2, blue syringe).