rTMS induces analgesia and modulates neuroinflammation and neuroplasticity in neuropathic pain model rats

Brain Res. 2021 Jul 1:1762:147427. doi: 10.1016/j.brainres.2021.147427. Epub 2021 Mar 15.

Abstract

Neuropathic pain (NP) is related to the presence of hyperalgesia, allodynia, and spontaneous pain, affecting 7%-10% of the general population. Repetitive transcranial magnetic stimulation (rTMS) is applied for NP relief, especially in patients with refractory pain. As NP response to existing treatments is often insufficient, we aimed to evaluate rTMS treatment on the nociceptive response of rats submitted to an NP model and its effect on pro-and anti-neuroinflammatory cytokine and neurotrophin levels. A total of 106 adult male Wistar rats (60 days old) were divided into nine experimental groups: control, control + sham rTMS, control + rTMS, sham NP, sham neuropathic pain + sham rTMS, sham neuropathic pain + rTMS, NP, neuropathic pain + sham rTMS, and neuropathic pain + rTMS. NP establishment was achieved 14 days after the surgery to establish chronic constriction injury (CCI) of the sciatic nerve. Rats were treated with 5 min daily sessions of rTMS for eight consecutive days. Nociceptive behavior was assessed using von Frey and hot plate tests at baseline, after NP establishment, and post-treatment. Biochemical assays to assess the levels of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-10, were performed in the prefrontal cortex (PFC) and spinal cord tissue homogenates. rTMS treatment promoted a partial reversal of mechanical allodynia and total reversal of thermal hyperalgesia induced by CCI. Moreover, rTMS increased the levels of BDNF, TNF-α, and IL-10 in the PFC. rTMS may be a promising tool for the treatment of NP. The alterations induced by rTMS on neurochemical parameters may have contributed to the analgesic effect presented.

Keywords: BDNF; Brain stimulation; Chronic pain; IL-10; Neuromodulation; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia / methods*
  • Animals
  • Disease Models, Animal*
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Male
  • Neuralgia / metabolism
  • Neuralgia / therapy*
  • Neuronal Plasticity / physiology*
  • Pain Measurement / methods
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Wistar
  • Spinal Cord / metabolism
  • Transcranial Magnetic Stimulation / methods*

Substances

  • Inflammation Mediators