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Publication : Single-cell analysis of dorsal root ganglia reveals metalloproteinase signaling in satellite glial cells and pain.

First Author  Tonello R Year  2023
Journal  Brain Behav Immun Volume  113
Pages  401-414 PubMed ID  37557960
Mgi Jnum  J:352501 Mgi Id  MGI:7538655
Doi  10.1016/j.bbi.2023.08.005 Citation  Tonello R, et al. (2023) Single-cell analysis of dorsal root ganglia reveals metalloproteinase signaling in satellite glial cells and pain. Brain Behav Immun 113:401-414
abstractText  Satellite glial cells (SGCs) are among the most abundant non-neuronal cells in dorsal root ganglia (DRGs) and closely envelop sensory neurons that detect painful stimuli. However, little is still known about their homeostatic activities and their contribution to pain. Using single-cell RNA sequencing (scRNA-seq), we were able to obtain a unique transcriptional profile for SGCs. We found enriched expression of the tissue inhibitor metalloproteinase 3 (TIMP3) and other metalloproteinases in SGCs. Small interfering RNA and neutralizing antibody experiments revealed that TIMP3 modulates somatosensory stimuli. TIMP3 expression decreased after paclitaxel treatment, and its rescue by delivery of a recombinant TIMP3 protein reversed and prevented paclitaxel-induced pain. We also established that paclitaxel directly impacts metalloproteinase signaling in cultured SGCs, which may be used to identify potential new treatments for pain. Therefore, our results reveal a metalloproteinase signaling pathway in SGCs for proper processing of somatosensory stimuli and potential discovery of novel pain treatments.
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