Related Experiment Video
Updated: Sep 22, 2025

Rapid Isolation of Dorsal Root Ganglion Macrophages
Published on: September 7, 2019
Microglia-mediated degradation of perineuronal nets promotes pain
Shannon Tansley1,2, Ning Gu1, Alba Ureña Guzmán1
1Department of Anesthesia, McGill University, Montreal, QC, Canada.
Abstract:
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.
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.
Related Concept Videos
Nociception
Neurogenesis and Regeneration of Nervous Tissue

