Sigma-1 receptor expression in sensory neurons and the effect of painful peripheral nerve injury.

ABSTRACT: The sigma-1 receptor (?1R), 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 ?1R is enriched in the spinal cord and modulates pain after peripheral nerve injury. However, ?1R expression in the DRG has not been studied. We therefore characterized ?1R expression in DRGs at baseline and following spinal nerve ligation (SNL) in rats.Immunohistochemical (IHC) studies in DRG sections show ?1R in both neuronal somata and satellite glial cells. The punctate distribution of ?1R in the neuronal cytoplasm suggests expression in the endoplasmic reticulum. When classified by neuronal size, large neurons (>1300 ?m) showed higher levels of ?1R staining than other groups (700-1300 ?m, <700 ?m). Comparing ?1R expression in neuronal groups characterized by expression of calcitonin gene-related peptide (CGRP), isolectin-B4 (IB4) and neurofilament-200 (NF-200), we found ?1R expression in all three neuronal subpopulations, with highest levels of ?1R expression in the NF-200 group. After SNL, lysates from L5 DRGs that contains axotomized neurons showed decreased ?1R protein but unaffected transcript level, compared with Control DRGs. IHC images also showed decreased ?1R 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 ?1R expression in L5 and, to a lesser extent, L4 DRGs. In IB4-labeled neurons, ?1R expression decreased only in axotomized L5 DRGs. Satellite cells also showed decreased ?1R expression in L5 DRGs after SNL.Our data show that ?1R is present in both sensory neurons and satellite cells in rat DRGs. Expression of ?1R 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 ?1R expression in neuropathic pain is not an explanation for pain relief after ?1R blockade. This implies that increased levels of endogenous ?1R agonists may play a role, and diminished neuroprotection from loss of glial ?1R may be a contributing factor.

SUBMITTER: Bangaru ML 

PROVIDER: S-EPMC3847629 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature