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Helena MRC Freire

Laboratory of Neuroscience, Brazil

Title: Percutaneous auricular vagus nerve stimulation prevents the oxaliplatin-induced neuropathic pain in rats by modulating the spinal neuronal and glial hyperactivation

Biography

Biography: Helena MRC Freire

Abstract

Oxaliplatin-Induced Neuropathic Pain (OINP) negatively impacts the patients' quality of life. OINP preventive or symptomatic treatments are generally ineffective, so the investigation of new therapeutic approaches is required. In this sense, we aimed to investigate the preemptive effect of percutaneous auricular Vagus Nerve Stimulation (paVNS) on OINP in rats.

Male Wistar rats were injected with Oxaliplatin (OXA) or saline (i.p) for two weeks, three times per week. paVNS was applied for 30 min, in a non-sequential random low frequency previously to each OXA session. maVNS had the needles inserted, but without stimulation. Animals were evaluated for hyperalgesia and allodynia, mechanical and thermal, before, immediately and after the end of treatments. Depressive-like behavior was evaluated six days after the end of treatment. The neuronal (Egr-1), microglial (Iba-1) and astrocytic (GFAP) immunoreactivity was investigated in the Spinal Dorsal Horn (SDH). Study approved by the Ethics Committee on the Use of Animals at Hospital Sírio-Libanês (CEUA 2021-03).

The OXA sessions induced thermal (p˂0.0092) and mechanical (p˂0.0005) hyperalgesia; thermal (p˂0.0113) and mechanical (p˂0.0049) allodynia and depressive-like behavior (p˂0.0001) in the rats immediately 3,5 and 7 days after the OXA treatment when compared with saline rats. paVNS treatment prevented all OPIN phenomena and the depressive-like behavior. maVNS therapy attenuated the painful behaviors, which was not maintained over time. Also, paVNS treatment reduced the OXA-induced hyperactivation of neurons (p˂0.0001) microglia (p=0.0043) and astrocyte (p˂0.0001) in the SDH, comparing with OXA and saline groups.

The preemptive use of paVNS inhibited the OXA-induced painful and depressive behaviors, which was accompanied by reversion of spinal glial and neuronal hyper activation. Our findings contribute to a better understanding of the functional mechanisms of vagal stimulation, elucidating its potential therapeutic value in OINP management.