Effect of preemptive treatment with percutaneous auricular vagus nerve stimulation in oxaliplatin-induced neuropathic pain: a preclinical study

• Grant number: 21/05654-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2021
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosana de Lima Pagano
• Grantee: Helena Martins Ribeiro da Cunha Freire
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

Chemotherapy-induced neuropathic pain (CINP) pain, such as oxaliplatin, has a very high prevalence (between 50 and 80% of cases) negatively impacting the quality of life of patients and may lead to treatment discontinuation. CINP preventive or symptomatic treatments are generally ineffective, making it necessary to investigate new therapeutic approaches to prevent or improve these symptoms. In this sense, percutaneous auricular vagus nerve stimulation (paVNS), a non-pharmacological treatment and non-invasive, appears to be effective in modulating CINP; however, its protective value against the emergence of this phenomenon has not yet been demonstrated. Therefore, this project aims to evaluate the efficacy of paVNS in preventing CINP, as well as its analgesic mechanisms, in a preclinical model of neuropathic pain induced by oxaliplatin. Rats will receive paVNS therapy prior to each cycle of oxaliplatin. Untreated animals, treated with the sham paVNS or without CINP will also be investigated. The nociceptive response will be investigated; peripheral sensitization in the sciatic nerve (expression of algesic factors, cytokines and acetylcholinergic receptor); activation of satellite cells in the dorsal root ganglion; central sensitization in the spinal cord (expression of algesic and analgesic factors and glial activation pattern) and expression of ²-endorphin and substance P in peripheral blood. We believe that this work will contribute to a better understanding the functional mechanisms of this technique, in addition to elucidating its potential therapeutic value, guiding the management of cancer patients for the prevention of persistent pain.