Microglia-mediated degradation of perineuronal nets promotes pain

Shannon Tansley1,2, Ning Gu1, Alba Ureña Guzmán1

  • 1Department of Anesthesia, McGill University, Montreal, QC, Canada.

Science (New York, N.Y.)
|May 26, 2022
PubMed

Insights

Peripheral nerve injury activates microglia, causing them to degrade perineuronal nets (PNNs) in the spinal cord. This PNN degradation enhances pain signaling, leading to hypersensitivity.

Area of Science:

  • Neuroscience
  • Pain Research
  • Cell Biology

Background:

  • Microglia activation in the spinal cord dorsal horn is linked to pain hypersensitivity after nerve injury.
  • The precise mechanisms by which microglia enhance spinal nociceptive circuit activity remain unclear.

Purpose of the Study:

  • To investigate how activated microglia selectively amplify spinal nociceptive circuits following peripheral nerve injury.
  • To elucidate the role of microglia-mediated extracellular matrix remodeling in pain hypersensitivity.

Main Methods:

  • Investigated microglia activation and extracellular matrix changes in the spinal cord dorsal horn after peripheral nerve injury.
  • Focused on the role of perineuronal nets (PNNs) and their degradation by microglia.
  • Examined the impact on spinoparabrachial projection neurons and pain-related behaviors.

Main Results:

  • Peripheral nerve injury triggers microglia to degrade perineuronal nets (PNNs) in lamina I of the spinal cord dorsal horn.
  • PNNs in lamina I selectively ensheath spinoparabrachial projection neurons, crucial for transmitting pain signals.
  • Microglial degradation of PNNs enhances spinoparabrachial neuron activity, promoting pain hypersensitivity and related behaviors.

Conclusions:

  • Microglia-induced degradation of PNNs is a key mechanism underlying enhanced spinal nociceptive circuit output after nerve injury.
  • This process selectively augments pain signaling, contributing significantly to the development of pain hypersensitivity.