Microglia-mediated degradation of perineuronal nets promotes pain

Science. 2022 Jul;377(6601):80-86. doi: 10.1126/science.abl6773. Epub 2022 May 26.


Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to the development of pain hypersensitivity. How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that after peripheral nerve injury, microglia degrade extracellular matrix structures, perineuronal nets (PNNs), in lamina I of the spinal cord dorsal horn. Lamina I PNNs selectively enwrap spinoparabrachial projection neurons, which integrate nociceptive information in the spinal cord and convey it to supraspinal brain regions to induce pain sensation. Degradation of PNNs by microglia enhances the activity of projection neurons and induces pain-related behaviors. Thus, nerve injury-induced degradation of PNNs is a mechanism by which microglia selectively augment the output of spinal nociceptive circuits and cause pain hypersensitivity.

MeSH terms

  • Animals
  • Extracellular Matrix / pathology
  • Hyperalgesia* / etiology
  • Hyperalgesia* / pathology
  • Hyperalgesia* / physiopathology
  • Microglia* / pathology
  • Pain* / pathology
  • Pain* / physiopathology
  • Peripheral Nerve Injuries* / complications
  • Peripheral Nerve Injuries* / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Dorsal Horn* / pathology
  • Spinal Cord Dorsal Horn* / physiopathology

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