Participation of descending serotonergic analgesia pathway and changes in inflammatory and neurodegenerative response in the treatment of neuropathic pain by transcranial direct-current stimulation

Abstract

Neuropathic pain (NP), resulting from injury or dysfunction of the nervous system somatosensory, generates a complex disease which treatment is difficult, resulting in a serious public health problem. New therapeutic approaches are needed as an alternative for patients refractory to pharmacological and surgical interventions. Accordingly, the transcranial direct-current stimulation (tDCS) has shown promising results in the treatment of NP and attracted great interest because it is a non-invasive technique of low cost, minimal side effects and restricted contraindications to very specific cases. Despite its applications in the clinic, its therapeutic mechanisms are poorly understood. In this project, we will evaluate in an experimental model of NP, the pattern of neuronal and glial activation, inflammatory mediators, neurotrophic factors and spinal and peripheral degeneration and participation of descending serotonergic analgesia pathway in animals submitted or not to treatment with repetitive tDCS on the motor cortex. Therefore, male Wistar rats will be submitted to peripheral neuropathy, evaluated at hyperalgesia and allodynia testing and undergo 10 sessions of tDCS (250 µA/15 min). Samples of nerve, dorsal ganglia, spinal cord and serum will be evaluated for cell activation, regeneration and expression of cytokines and neurotrophic factors. Samples of magnus (NRM) and dorsal (DRN) raphe nuclei will be evaluated for c-Fos and serotonin labeling. It will also investigate by pharmacological block, the involvement of descending serotonergic analgesia pathway using a specific antagonist of 5HT1A serotonergic receptor. Also, it will be determined the duration of the therapeutic effect of tDCS. The data obtained from this project may help the understanding of the mechanisms of action involved in analgesia induced by tDCS, elucidating its potential therapeutic value and enabling better targeting in the treatment of DN. (AU)