3 years ago

IKK/NF-κB-dependent satellite glia activation induces spinal cord microglia activation and neuropathic pain after nerve injury

Noh, Kyungchul, Lee, Hyunkyoung, Lim, Hyoungsub, Lee, Sung Joong
imageAbstract: Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre+/−/Ikkβf/f; cIkkβ−/−) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury–induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice. In addition, nerve injury–induced proinflammatory gene expression and macrophage infiltration into the dorsal root ganglion (DRG) were severely compromised. However, macrophages recruited into the DRG had minimal effects on spinal cord microglia activation, suggesting a causal effect for SGC activation on spinal cord microglia activation. In an effort to elucidate the molecular mechanisms, we measured Csf1 expression in the DRG, which is implicated in spinal cord microglia activation after nerve injury. In cIkkβ−/− mice, nerve injury–induced Csf1 upregulation was ameliorated indicating that IKK/NF-κΒ-dependent SGC activation induced Csf1 expression in sensory neurons. Taken together, our data suggest that nerve injury–induced SGC activation triggers Csf1 induction in sensory neurons, spinal cord microglia activation, and subsequent central pain sensitization.
You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.