Microglia-mediated degradation of perineuronal nets promotes pain-Reference-Cited by-同舟云学术

Microglia-mediated degradation of perineuronal nets promotes pain

Published:2022-07 Issue:6601 Volume:377 Page:80-86
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Tansley Shannon¹²^ORCID,Gu Ning¹^ORCID,Guzmán Alba Ureña¹,Cai Weihua¹,Wong Calvin¹^ORCID,Lister Kevin C.¹^ORCID,Muñoz-Pino Einer³^ORCID,Yousefpour Noosha⁴^ORCID,Roome R. Brian⁵,Heal Jordyn¹^ORCID,Wu Neil¹^ORCID,Castonguay Annie³^ORCID,Lean Graham⁶^ORCID,Muir Elizabeth M.⁷,Kania Artur⁵⁸,Prager-Khoutorsky Masha⁶^ORCID,Zhang Ji⁹¹⁰¹¹^ORCID,Gkogkas Christos G.¹²^ORCID,Fawcett James W.¹³¹⁴^ORCID,Diatchenko Luda¹¹⁰¹¹^ORCID,Ribeiro-da-Silva Alfredo⁴⁸¹¹^ORCID,De Koninck Yves³⁴¹¹^ORCID,Mogil Jeffrey S.¹²¹¹^ORCID,Khoutorsky Arkady¹¹⁰¹¹^ORCID

Affiliation:

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

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

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

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

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

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

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

8. Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada.

9. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

10. Faculty of Dental Medicine and Oral Health Sciences, Montreal, QC, Canada.

11. Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada.

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

13. John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

14. Centre for Reconstructive Neuroscience, Institute for Experimental Medicine CAS, Prague, Czech Republic.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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