Microglia-mediated degradation of perineuronal nets promotes pain
Activation of microglia in the spinal cord dorsal horn following 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 following peripheral ne...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2022-07, Vol.377 (6601), p.eabl6773-86 |
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| creator | Tansley, Shannon Gu, Ning Guzmán, Alba Ureña Cai, Weihua Wong, Calvin Lister, Kevin Muñoz-Pino, Einer Yousefpour, Noosha Roome, R Brian Heal, Jordyn Wu, Neil Castonguay, Annie Lean, Graham Muir, Elizabeth M Kania, Artur Prager-Khoutorsky, Masha Zhang, Ji Gkogkas, Christos G Fawcett, James W Diatchenko, Luda Ribeiro-da-Silva, Alfredo De Koninck, Yves Mogil, Jeffrey S Khoutorsky, Arkady |
| description | Activation of microglia in the spinal cord dorsal horn following 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 following 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. |
| doi_str_mv | 10.1126/science.abl6773 |
| format | Article |
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How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that following 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. 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How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that following 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.</description><subject>Chronic pain</subject><subject>Dorsal horn</subject><subject>Extracellular matrix</subject><subject>Horns</subject><subject>Hypersensitivity</subject><subject>Injuries</subject><subject>Microglia</subject><subject>Nets</subject><subject>Neurons</subject><subject>Pain</subject><subject>Perineuronal nets</subject><subject>Peripheral nerves</subject><subject>Projection</subject><subject>Spinal cord 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How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that following 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. 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| subjects | Chronic pain Dorsal horn Extracellular matrix Horns Hypersensitivity Injuries Microglia Nets Neurons Pain Perineuronal nets Peripheral nerves Projection Spinal cord injuries |
| title | Microglia-mediated degradation of perineuronal nets promotes pain |
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