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Papers of the Week

Papers: 1 May 2021 - 7 May 2021

Animal Studies

2021 Apr 30


β2 adrenergic receptor mediates noradrenergic action to induce CREB phosphorylation in satellite glial cells of dorsal root ganglia to regulate visceral hypersensitivity.


Sympathoneuronal outflow into dorsal root ganglia (DRG) is suggested to be involved in sympathetically maintained chronic pain, which is mediated by norepinephrine (NE) action on DRG cells. The present study combined in vitro and in vivo approaches to identify the cell types of DRG that received NE action and examined cell-type specific expression of adrenergic receptors (ARs) in DRG. Using DRG explants, we identified that NE acted on satellite glial cells (SGCs) to induce the phosphorylation of cAMP response element-binding (CREB). Using primarily cultured SGCs, we identified that beta (β)2AR but not alpha (α)AR nor other βAR isoforms mediated NE-induced CREB phosphorylation and CRE-promoted luciferase transcriptional activity. Using fluorescence in situ hybridization and affinity purification of mRNA from specific cell types, we identified that β2AR was expressed by SGCs but not DRG neurons. We further examined β2AR expression and CREB phosphorylation in vivo in a model of colitis in which sympathetic nerve sprouting in DRG was observed. We found that β2AR expression and CREB phosphorylation were increased in SGCs of thoracolumbar DRG on day 7 following colitis induction. Inhibition but not augmentation of β2AR reduced colitis- induced calcitonin gene-related peptide (CGRP) release into the spinal cord dorsal horn and colonic pain responses to colorectal distention. Prolonged activation of β2AR in naïve DRG increased CGRP expression in DRG neurons. These findings provide molecular basis of sympathetic modulation of sensory activity and chronic pain that involves β2AR-mediated signaling in SGCs of DRG.