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

• Grant number: 22/10532-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosana de Lima Pagano
• Grantee: Rosana de Lima Pagano
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
• Associated researchers: Cibele Masotti ; Paula Fontes Asprino

Abstract

Chemotherapy-induced neuropathic pain (CINP) 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. Preventive or symptomatic treatments for CINP are generally ineffective, making it necessary to investigate new therapeutic approaches that prevent or improve these symptoms. In this sense, percutaneous auricular vagal nerve stimulation (paVNS), a non-pharmacological and non-invasive treatment, seems to be effective in modulating CINP; however, its protective value against the onset of this phenomenon has not been demonstrated yet. Previous results obtained by our group demonstrated that paVNS treatment is able to prevent oxaliplatin-induced CINP in rats, this response being accompanied by inhibition of hyperactivation of spinal neurons, microglia and astrocytes. In order to further investigate the mechanisms involved in this response, we will investigate the peripheral sensitization in the sciatic nerve (expression of algesic factors, cytokines and acetylcholinergic receptor); the activation of satellite cells in the dorsal root ganglion (DRG); the central sensitization in the spinal cord (expression of algesic and analgesic factors); the systemic expression of ²-endorphin and substance P and the modulation of the descending serotoninergic pathway. In addition, the identification of differentially expressed transcripts in DRG will be performed in order to find new therapeutic targets for CINP and elucidate the mechanisms of action of paVNS. This project aims to contribute to a better understanding of the preemptive mechanisms of vagal auricular stimulation in CINP and to elucidate its potential therapeutic value, guiding the management of cancer patients for the prevention of persistent pain. (AU)