Transcranial direct current stimulation alters anxious-like behavior and neural parameters in rats with chronic pain exposed to alcohol

The aim of this study was to evaluate the effects of transcranial direct current stimulation (tDCS) on anxiety-like behavior and neural parameters in rats with chronic pain exposed to alcohol. Thirty-six adult male Wistar rats were randomly assigned to control (CT), neuropathic pain (NP), NPtDCS, NP + alcohol (NPAL), or NPALtDCS groups, subjected to sciatic nerve chronic constriction injury (CCI) and exposed to alcohol (20% v/v solution, 4 g/kg) or vehicle by gavage for 15 days. Afterward, rats were treated using bimodal tDCS (0.5 mA/20 min/8 days) and tested in the open field. Rats were killed 24 h after the last behavioral assessment, and brain and spinal cord tissue samples were collected and processed for NPY immunohistochemistry, expression of Il1a and Il1b in the spinal cord, cerebellum, and hippocampus, and levels of IL-1α and IL-1β in the same brain structures and the striatum. tDCS reverted the anxiety-like behavior induced by CCI and alcohol, and the increased expression of Il1a in the spinal cord induced by alcohol, which increased the expression of Il1b in the cerebellum. In addition, tDCS modulated the hypothalamic NPY-immunoreactivity, increased the levels of IL-1α in the hippocampus (like NP and AL), and increased the expression of Il1b in the spinal cord (like AL). Thus, this study shows that tDCS changes NP and alcohol-induced anxiety-like behavior, possibly through its central modulatory effect of NPY and spinal cord expression of Il1a and Il1b, being considered a treatment option for alcohol and NP-induced anxiety symptoms. Rats were subjected to sciatic nerve chronic constriction injury (CCI). 2: After CCI surgery, rats received alcohol (20% v/v solution, 4 g/kg) or vehicle by gavage for fifteen days. 3: Then, rats were treated using bimodal Transcranial Direct Current Stimulation (tDCS - 0.5mA/20 min/8 days). 4: all rats were tested twice in the Open Field (right before and after ending tDCS treatment). 5: at the end of the behavioral assessment, rats were killed and brain and spinal cord tissue samples were collected to analyze the immunoreactivity (Immunohistochemistry) of NPY in the hippocampus, the expression (RT-PCR) of Il1a and Il1b in the spinal cord, cerebellum, and hippocampus, and levels (ELISA) of IL-1α and IL-1β in the spinal cord, cerebellum, hippocampus, and striatum. Created with BioRender. [Display omitted] •Chronic pain and ethanol exposure induce anxiety activating specific brain circuits.•Both conditions induce centr