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Stimulation of nuclear receptor REV-ERBs suppresses inflammatory responses in spinal microglia

Norimitsu Morioka1, Keitaro Kodama1, Maho Tsuruta1

  • 1Department of Pharmacology, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.

Neurochemistry International
|October 28, 2021
PubMed

Insights

REV-ERB nuclear receptors regulate spinal microglia activity, offering a potential pathway for chronic pain relief. Targeting these receptors may reduce pain by dampening neuroinflammation.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Spinal microglia play a key role in chronic pain development.
  • REV-ERB nuclear receptors stimulation in the spinal dorsal horn shows antinociceptive effects in pain models.
  • The specific role of spinal microglia in REV-ERB-mediated antinociception is not fully understood.

Purpose of the Study:

  • To investigate the involvement of spinal microglia in the antinociceptive effects of REV-ERB activation.
  • To determine if REV-ERBs regulate spinal microglial activity.

Main Methods:

  • Intrathecal administration of the REV-ERB agonist SR9009 in mouse models of inflammatory and neuropathic pain.
  • Assessment of ionized calcium-binding adaptor molecule immunoreactivity in the spinal dorsal horn.
  • Analysis of Rev-erbα and Rev-erbβ mRNA expression in cultured rat spinal microglia.
  • Evaluation of SR9009's effect on lipopolysaccharide-induced interleukin (IL)-1β and IL-6 mRNA expression in microglia.

Main Results:

  • SR9009 treatment significantly blocked the increase in ionized calcium-binding adaptor molecule immunoreactivity in the spinal dorsal horn.
  • Both Rev-erbα and Rev-erbβ mRNAs were detected in cultured rat spinal microglia.
  • SR9009 inhibited the lipopolysaccharide-induced upregulation of IL-1β and IL-6 mRNA in microglia.

Conclusions:

  • REV-ERBs negatively regulate spinal microglial activity.
  • REV-ERBs may contribute to antinociception in the spinal dorsal horn by modulating microglial function.
Keywords:
Chronic painInterleukin-1βInterleukin-6MicrogliaREV-ERBsSpinal dorsal horn

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