Repetitive transcranial magnetic stimulation (rTMS) alters biomarkers in prefrontal cortex of rats submitted to a neuropathic pain model

Roberta Ströher Toledo 1,2; Dirson João Stein 2,3; Paulo Roberto Stefani Sanches 4; Lisiane Santos da Silva 2,3; Helouise Richardt Medeiros 2,3; Wolnei Caumo 3, Iraci LS Torres 1,2,3

  1. Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica – Instituto de Ciências Básicas da Saúde - Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
  2. Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-clínicas – Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  3. Programa de Pós-Graduação em Medicina: Ciências Médicas - Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
  4. Serviço de Pesquisa e Desenvolvimento em Engenharia Biomédica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

OBJECTIVE: To evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) over biomarkers in prefrontal cortex (PFC) of rats submitted to a neuropathic pain (NP) model.

METHODS: 63 male Wistar rats (± 60 days) were initially divided into 3 groups to induce the pain model: Control (without manipulation), Sham NP (surgery without nerve constriction) and NP (sciatic nerve constriction surgery). Later, animals were subdivided into: without treatment, Sham rTMS and rTMS, totalizing 9 groups. For the treatment with rTMS, 5min daily sessions were applied for 8 consecutive days. For Sham rTMS treatment, the magnetic generator remained off. 48h after the end of treatment, animals were euthanized by decapitation, and the PFC was collected for brain-derived neutrophic factor (BDNF), tumor necrosis factor alpha (TNF-?) and interleukin 10 (IL-10) analysis, measured by ELISA. Data analyzed by one-way ANOVA/SNK, P <0.05. CEUA/HCPA approval #2017-0438.

RESULTS: Animals with NP treated with rTMS showed an increase in BDNF, TNF-? and IL-10 levels in PFC compared to others groups (F8,70 = 3.96; F8,66 = 8.81; F8,70 = 4.28, respectively, P <0.05).

CONCLUSIONS: rTMS altered cortical levels of BDNF, TNF-? and IL-10 only in animals with NP. This neuromodulatory effect of rTMS at the cortical level may have contributed to the analgesia previously found in these animals, modulating areas adjacent to the stimulation and related to the nociceptive process.

KEYWORDS: Neuromodulation, chronic pain, cytokine, neurotrophin.