, 2012). In this context, this study, to the best of our knowledge, was the first to show that tDCS can reverse the effects of maladaptive plasticity as expressed by behavioral changes and measured by TNFα levels. On the other hand, one limitation of the study was the lack of difference between one of the analysis for von Frey test – S vs. SN – probably because of less sensitivity of this measurement as compared to hot plate test and also because of differences what these measurements index such as hot plate related to hyperalgesia and von Frey related to allodynia. In summary, we showed that

tDCS was able to reverse completely the detrimental effects of chronic stress LDK378 on the pain system, as expressed by hyperalgesia and allodynia, and that this effect continued for 24 h. Serum levels of corticosterone and interleukin-1β were not changed by tDCS sessions or chronic restraint stress, but hippocampal TNFα levels decreased. Given that, in this study, animals were exposed to the same level of stress under the same

BTK inhibitor conditions, our findings support further exploration of tDCS as a therapeutic tool early in the exposure to stressful situations that may lead to chronic pain, such as post-traumatic stress disorder, and demonstrate one possible pathway of anodal tDCS treatment. Future studies should also consider assessing other outcomes of stress response, including other behavioral outcomes, as well as measurement of other biochemical variables, such as PCPA (inhibitor of serotonin synthesis), AMPT (inhibitor of tyrosine hydroxylase) and naloxone, to provide a better understanding of the effects of chronic restraint stress on mood and anxiety and further elucidate and

optimize this intervention into a potential clinical tool for stress-related conditions. Sixty-day-old male Wistar rats weighing 180–230 g were used. Experimentally naive animals were housed in groups of five in 49×34×16 cm polypropylene home cages. All animals were kept on a standard 12-hour light/dark cycle (lights Galeterone on at 07:00 a.m. and lights off at 07:00 p.m.) in a temperature-controlled environment (22±2 °C). Animals had access to water and chow ad libitum. All experiments and procedures were approved by the Institutional Committee for Animal Care and Use (GPPG-HCPA protocol No. 100.381) and performed in accordance with the Guide for the Care and Use of Laboratory Animals 8th edition (2011). Animal handling and all experiments were performed in accordance with International Guidelines for Animal Welfare and Measures were taken to minimize animal pain and discomfort. The experiment used the minimum number of animals required to produce reliable scientific data. To control the possible effect of outliers, we excluded rats which did not present any response on behavioral testing. All the experimenters were blinded to condition (active or sham tDCS) during post-treatment behavioral testing.