A spinal microglia population involved in remitting and relapsing neuropathic pain

Science. 2022 Apr;376(6588):86-90. doi: 10.1126/science.abf6805. Epub 2022 Mar 31.

Abstract

Neuropathic pain is often caused by injury and diseases that affect the somatosensory system. Although pain development has been well studied, pain recovery mechanisms remain largely unknown. Here, we found that CD11c-expressing spinal microglia appear after the development of behavioral pain hypersensitivity following nerve injury. Nerve-injured mice with spinal CD11c+ microglial depletion failed to recover spontaneously from this hypersensitivity. CD11c+ microglia expressed insulin-like growth factor-1 (IGF1), and interference with IGF1 signaling recapitulated the impairment in pain recovery. In pain-recovered mice, the depletion of CD11c+ microglia or the interruption of IGF1 signaling resulted in a relapse in pain hypersensitivity. Our findings reveal a mechanism for the remission and recurrence of neuropathic pain, providing potential targets for therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • CD11 Antigens / genetics
  • CD11 Antigens / metabolism
  • Chronic Pain / physiopathology*
  • Female
  • Hyperalgesia / physiopathology*
  • Luminescent Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / physiology*
  • Neuralgia / physiopathology*
  • Peripheral Nerve Injuries / physiopathology*
  • Recurrence
  • Spinal Cord / physiopathology*

Substances

  • Bacterial Proteins
  • CD11 Antigens
  • Itgax protein, mouse
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria