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Molecular Pain

, 9:47

First Online: 10 September 2013Received: 27 June 2013Accepted: 07 September 2013

Abstract

BackgroundThe sigma-1 receptor σ1R, an endoplasmic reticulum chaperone protein, is widely distributed and regulates numerous intracellular processes in neurons. Nerve injury alters the structure and function of axotomized dorsal root ganglion DRG neurons, contributing to the development of pain. The σ1R is enriched in the spinal cord and modulates pain after peripheral nerve injury. However, σ1R expression in the DRG has not been studied. We therefore characterized σ1R expression in DRGs at baseline and following spinal nerve ligation SNL in rats.

ResultsImmunohistochemical IHC studies in DRG sections show σ1R in both neuronal somata and satellite glial cells. The punctate distribution of σ1R in the neuronal cytoplasm suggests expression in the endoplasmic reticulum. When classified by neuronal size, large neurons >1300 μm showed higher levels of σ1R staining than other groups 700-1300 μm, <700 μm. Comparing σ1R expression in neuronal groups characterized by expression of calcitonin gene-related peptide CGRP, isolectin-B4 IB4 and neurofilament-200 NF-200, we found σ1R expression in all three neuronal subpopulations, with highest levels of σ1R expression in the NF-200 group. After SNL, lysates from L5 DRGs that contains axotomized neurons showed decreased σ1R protein but unaffected transcript level, compared with Control DRGs. IHC images also showed decreased σ1R protein expression, in SNL L5 DRGs, and to a lesser extent in the neighboring SNL L4 DRGs. Neurons labeled by CGRP and NF-200 showed decreased σ1R expression in L5 and, to a lesser extent, L4 DRGs. In IB4-labeled neurons, σ1R expression decreased only in axotomized L5 DRGs. Satellite cells also showed decreased σ1R expression in L5 DRGs after SNL.

ConclusionsOur data show that σ1R is present in both sensory neurons and satellite cells in rat DRGs. Expression of σ1R is down-regulated in axotomized neurons as well as in their accompanying satellite glial cells, while neighboring uninjured neurons show a lesser down-regulation. Therefore, elevated σ1R expression in neuropathic pain is not an explanation for pain relief after σ1R blockade. This implies that increased levels of endogenous σ1R agonists may play a role, and diminished neuroprotection from loss of glial σ1R may be a contributing factor.

KeywordsSigma-1 receptor Neuropathic pain Peripheral nerve injury Endoplasmic reticulum Sensory neuron Dorsal root ganglion AbbreviationsSNLSpinal nerve ligation

CNSCentral nervous system

DRGDorsal root ganglion

SGCSatellite glial cells

σ1RSigma-1 receptor

IB4Isolectin-4

CGRPCalcitonin gene-related protein

NeuNNeuron-specific nuclear protein

NF-200Neurofilament 200

IHCImmunohistochemical.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-9-47 contains supplementary material, which is available to authorized users.

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Autor: Madhavi L Bangaru - Dorothee Weihrauch - Qing-Bo Tang - Vasiliki Zoga - Quinn Hogan - Hsiang-en Wu

Fuente: https://link.springer.com/



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