Plp1-expresssing perineuronal DRG cells facilitate colonic and somatic chronic mechanical pain involving Piezo2 upregulation in DRG neurons.

Autor: Tiwari N; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0551, USA., Smith C; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0551, USA., Sharma D; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0551, USA., Shen S; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0551, USA., Mehta P; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0551, USA., Qiao LY; Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0551, USA. Electronic address: liya.qiao@vcuhealth.org.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2024 May 28; Vol. 43 (5), pp. 114230. Date of Electronic Publication: 2024 May 13.
DOI: 10.1016/j.celrep.2024.114230
Abstrakt: Satellite glial cells (SGCs) of dorsal root ganglia (DRGs) are activated in a variety of chronic pain conditions; however, their mediation roles in pain remain elusive. Here, we take advantage of proteolipid protein (PLP)/creER T -driven recombination in the periphery mainly occurring in SGCs of DRGs to assess the role of SGCs in the regulation of chronic mechanical hypersensitivity and pain-like responses in two organs, the distal colon and hindpaw, to test generality. We show that PLP/creER T -driven hM3Dq activation increases, and PLP/creER T -driven TrkB.T1 deletion attenuates, colon and hindpaw chronic mechanical hypersensitivity, positively associating with calcitonin gene-related peptide (CGRP) expression in DRGs and phospho-cAMP response element-binding protein (CREB) expression in the dorsal horn of the spinal cord. Activation of Plp1 + DRG cells also increases the number of small DRG neurons expressing Piezo2 and acquiring mechanosensitivity and leads to peripheral organ neurogenic inflammation. These findings unravel a role and mechanism of Plp1 + cells, mainly SGCs, in the facilitation of chronic mechanical pain and suggest therapeutic targets for pain mitigation.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE