Microglia-mediated degradation of perineuronal nets promotes pain.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Tansley, S; Gu, N; Guzmán, AU; Cai, W; Wong, C; Lister, KC; Muñoz-Pino, E; Yousefpour, N; Roome, RB; Heal, J; Wu, N; Castonguay, A; Lean, G; Muir, EM; Kania, A; Prager-Khoutorsky, M; Zhang, J; Gkogkas, CG; Fawcett, JW; Diatchenko, L; Ribeiro-da-Silva, A; De Koninck, Y; Mogil, JS; Khoutorsky, A

Published Date

  • July 2022

Published In

Volume / Issue

  • 377 / 6601

Start / End Page

  • 80 - 86

PubMed ID

  • 35617374

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.abl6773

Language

  • eng

Conference Location

  • United States