Fig. 1.

Experimental design of the study and effect of cortical stimulation on mechanical nociceptive threshold. Rats were habituated to the nociceptive test the day preceding the electrode implantation (day 1). The paw pressure test was conducted prior to the electrode implantation (initial measurement, IM; day 2) and 7 days later (day 9), as well as before (final measurement 1, FM1) and during MCS (final measurement 2, FM2). Naive and sham rats were also evaluated. Animals were divided into three groups: rats with no surgical procedure (Naive), rats with transdural electrodes and false stimulation (Sham), and stimulated rats (MCS). The transdural electrodes were implanted over the motor cortex of the left hemisphere, and the nociceptive threshold of the right hind paw was determined. Values represent the mean ± SEM of 10 animals from each group. Statistically significant differences from the naive group (***p < 0.0001, after Bonferroni’s post hoc test) are indicated. Half of the animals in each group were perfused immediately after the last nociceptive test and evaluated for 5HT-, TH-, SP- and ENK-IR; the other half was perfused 1 h after the last nociceptive test for evaluation of Egr-1-IR. 5HT serotonin, ENK enkephalin, IR immunoreactivity, MCS motor cortex stimulation, SP substance P, TH tyrosine hydroxylase