Microglia-mediated degradation of perineuronal nets promotes pain

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.

Topics

No keywords indexed for this article. Browse by subject →

References

45

[1]

10.1038/nm.4397

[2]

10.1016/j.neuron.2018.11.009

[3]

10.1038/s41583-019-0196-3

[4]

10.1073/pnas.1815273115

[5]

10.1016/j.neuron.2017.06.028

[6]

10.1126/science.1072699

[7]

10.1523/jneurosci.2504-16.2016

[8]

10.1523/jneurosci.1122-18.2018

[9]

10.1002/cne.20822

[10]

10.1016/j.cophys.2019.10.002

[11]

10.1007/s00702-020-02159-1

[12]

10.1016/s0304-3959(00)00276-1

[13]

10.1067/s1526-5900(03)00781-8

[14]

10.1038/nmeth762

[15]

10.1523/eneuro.0448-18.2019

[16]

10.1128/mcb.20.11.4106-4114.2000

[17]

10.2353/ajpath.2010.100265

[18]

10.1002/glia.23016

[19]

10.1016/j.bbi.2015.07.024

[20]

A. A. Staniland, A. K. Clark, R. Wodarski, O. Sasso, F. Maione, F. D’Acquisto, M. Malcangio, Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice. J. Neurochem. 114, 1143–1157 (2010). 20524966 10.1111/j.1471-4159.2010.06837.x

[21]

10.1016/j.neuron.2016.09.021

[22]

10.1371/journal.pone.0264938

[23]

10.1016/j.jneumeth.2014.02.010

[24]

10.1038/416636a

[25]

10.1038/nrn2898

[26]

10.1002/cne.22437

[27]

10.1016/j.jneumeth.2008.10.024

[28]

10.1126/science.aaf8933

[29]

10.1038/nature01868

[30]

10.1016/j.celrep.2019.06.059

[31]

10.7554/elife.49753

[32]

10.1038/nn.4053

[33]

10.1016/j.bbi.2015.10.006

[34]

10.1038/ncomms12029

[35]

10.1523/jneurosci.0434-21.2021

[36]

10.1016/j.cell.2018.06.035

[37]

10.1016/j.celrep.2020.108425

[38]

10.1016/s0304-3959(00)00276-1

[39]

10.1038/nmeth.1455

[40]

10.1016/0165-0270(94)90144-9

[41]

10.1038/srep14306

[42]

10.1016/j.jbiotec.2009.11.002

[43]

10.1016/j.jneumeth.2011.08.003

[44]

10.1371/journal.pone.0186759

[45]

10.1177/1744806918764979

Cited By

176

Translational control in the spinal cord regulates gene expression and pain hypersensitivity in the chronic phase of neuropathic pain

Kevin C Lister, Calvin Wong · 2026

eLife

Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain

Jie Wu, Haijun Hu · 2025

Frontiers in Immunology

The gut microbiota promotes pain in fibromyalgia

Weihua Cai, May Haddad · 2025

Neuron

The deficient CLEC5A ameliorates the behavioral and pathological deficits via the microglial Aβ clearance in Alzheimer’s disease mouse model

Yu-Yi Lin, Wen-Han Chang · 2024

Journal of Neuroinflammation

Extracellular Matrix Regulation in Physiology and in Brain Disease

Alyssa Soles, Adem Selimovic · 2023

International Journal of Molecular...

Pain-resolving immune mechanisms in neuropathic pain

Nathan T. Fiore, Sophie R. Debs · 2023

Nature Reviews Neurology

Metrics

176

Citations

45

References

Details

Published: Jul 01, 2022
Vol/Issue: 377(6601)
Pages: 80-86

Authors

S

Shannon Tansley

Department of Anesthesia, McGill University, Montreal, QC, Canada.; Department of Psychology, Faculty of Science, McGill University, Montreal, QC, Canada.

N

Ning Gu

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

A

Alba Ureña Guzmán

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

W

Weihua Cai

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

C

Calvin Wong

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

K

Kevin C. Lister

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

E

Einer Muñoz-Pino

Department of Psychiatry and Neuroscience, CERVO Brain Research Centre, Université Laval, Québec, QC, Canada.

N

Noosha Yousefpour

Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.

R

R. Brian Roome

Institut de Recherches Cliniques de Montreal (IRCM), Montreal, QC, Canada.

J

Jordyn Heal

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

N

Neil Wu

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

A

Annie Castonguay

Department of Psychiatry and Neuroscience, CERVO Brain Research Centre, Université Laval, Québec, QC, Canada.

G

Graham Lean

Department of Physiology, McGill University, Montreal, QC, Canada.

E

Elizabeth M. Muir

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.

A

Artur Kania

Institut de Recherches Cliniques de Montreal (IRCM), Montreal, QC, Canada.; Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.

M

Masha Prager-Khoutorsky

Department of Physiology, McGill University, Montreal, QC, Canada.

J

Ji Zhang

Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.; Faculty of Dental Medicine and Oral Health Sciences, Montreal, QC, Canada.; Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

C

Christos G. Gkogkas

Biomedical Research Institute, Foundation for Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece.

J

James W. Fawcett

John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.; Centre for Reconstructive Neuroscience, Institute for Experimental Medicine CAS, Prague, Czech Republic.

L

Luda Diatchenko

Department of Anesthesia, McGill University, Montreal, QC, Canada.; Faculty of Dental Medicine and Oral Health Sciences, Montreal, QC, Canada.; Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

A

Alfredo Ribeiro-da-Silva

Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.; Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.; Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

Y

Yves De Koninck

Department of Psychiatry and Neuroscience, CERVO Brain Research Centre, Université Laval, Québec, QC, Canada.; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.; Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

J

Jeffrey S. Mogil

Department of Anesthesia, McGill University, Montreal, QC, Canada.; Department of Psychology, Faculty of Science, McGill University, Montreal, QC, Canada.; Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

A

Arkady Khoutorsky

Department of Anesthesia, McGill University, Montreal, QC, Canada.; Faculty of Dental Medicine and Oral Health Sciences, Montreal, QC, Canada.; Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

Cite This Article

Shannon Tansley, Ning Gu, Alba Ureña Guzmán, et al. (2022). Microglia-mediated degradation of perineuronal nets promotes pain. Science, 377(6601), 80-86. https://doi.org/10.1126/science.abl6773

Microglia-mediated degradation of perineuronal nets promotes pain

You May Also Like