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.

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

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

Centre for Reconstructive Neuroscience Institute for Experimental Medicine CAS Prague Czech Republic

Department of Anatomy and Cell Biology McGill University Montreal QC Canada

Department of Anesthesia McGill University Montreal QC Canada

Department of Neurology and Neurosurgery McGill University Montreal QC Canada

Department of Pharmacology and Therapeutics McGill University Montreal QC Canada

Department of Physiology Development and Neuroscience University of Cambridge Cambridge UK

Department of Physiology McGill University Montreal QC Canada

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

Department of Psychology Faculty of Science McGill University Montreal QC Canada

Faculty of Dental Medicine and Oral Health Sciences Montreal QC Canada

Institut de Recherches Cliniques de Montreal Montreal QC Canada

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

Signal Transduct Target Ther. 2022 Sep 22;7(1):333. doi: 10.1038/s41392-022-01162-0. PubMed

References provided by Crossref.org

High-Intensity Interval Training Increases Osteoarthritis-Associated Pain-Sensitive Threshold Through Reduction of Perineuronal Nets of the Medial Prefrontal Cortex in Rats