G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal cord neurons is involved in neuropathic pain

Abstract

BackgroundG protein-coupled receptor, family C, group 5 (GPRC5B), a retinoic acid-inducible orphan G-protein-coupled receptor (GPCR), is a member of the group C metabotropic glutamate receptor family proteins presumably related in non-canonical Wnt signaling. In this study, we investigated altered GPRC5B expression in the dorsal horn of the spinal cord after spinal nerve injury and its involvement in the development of neuropathic pain.MethodsAfter induction of anesthesia by intraperitoneal injection of pentobarbital (35 mg /kg), the left L5 spinal nerve at the level of 2 mm distal to the L5 DRG was tightly ligated with silk and cut just distal to the ligature. Seven days after nerve injury, animals were perfused with 4% paraformaldehyde, and the spinal cords were extracted and post-fixed at 4℃ overnight. To identify the expression of GPRC5B and analyze the involvement of GPRC5B in neuropathic pain, immunofluorescence was performed using several markers for neurons and glial cells in spinal cord tissue.ResultsAfter L5 spinal nerve ligation (SNL), the expression of GPRC5B was decreased in the ipsilateral part, as compared to the contralateral part, of the spinal dorsal horn. SNL induced the downregulation of GPRC5B in NeuN-positive neurons in the spinal dorsal horn. However, CNPase-positive oligodendrocytes, OX42-positive microglia, and GFAP-positive astrocytes were not immunolabeled with GPRC5B antibody in the spinal dorsal horn.ConclusionsThese results imply that L5 SNL-induced GPRC5B downregulation may affect microglial activation in the spinal dorsal horn and be involved in neuropathic pain.

The involvement of <i>GPRC5B</i> in cadmium toxicity in HK-2 cells

“…These results suggest that Cd may strengthen its toxicity via the suppression of GPRC5B gene expression in HK-2 cells. Several studies demonstrated that GPRC5B might be involved in neuropathic pain and insulin secretion (Soni et al, 2013;Chung et al, 2014). However, the role of GPRC5B in kidney function or Cd-induced renal toxicity has not been elucidated.…”

Implication of Hypothalamus in Alleviating Spinal Cord Injury-Induced Neuropathic Pain

“…G protein-coupled receptor, family C, group 5 (GPRC5B) have been shown to be related in non-canonical WNT signaling. Down-regulation of GPRC5B in the dorsal horn of the spinal cord neurons is correlated with an increased NP following a SCI [30] . Not only have GPCRs, such as GPRC5B, been shown as an evidence of NP in the SCI, but GCPRs have also been detected in the paraventricular nucleus and supraoptic nucleus of the hypothalamus [31] .…”

“…Some chronic pain conditions such as rheumatoid arthritis and fibromyalgia have been directly linked to abnormalities in the hypothalamo-pituitaryadrenal axis (HPA); however, the role of HPA axis on NP is currently unknown [29] . Gene-protein coupled receptors (GPCRs) are the major targets for hormones, neurotransmitters, neuropeptides in the nervous system, and are important for drug development targeting NP [30] . G protein-coupled receptor, family C, group 5 (GPRC5B) have been shown to be related in non-canonical WNT signaling.…”

Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson’s Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra

“…GPR5B codes for a G protein-coupled receptor, which is a member of the group C metabotropic glutamate receptor family. This protein is required for neuronal fate determination in the brain [ 45 ] and GPR5B downregulation affects microglial activation [ 75 ]. Directly linked to GPR5B ( Figure 3 ) appears PCOLCE2 , a gene coding for a procollagen C-proteinase enhancer [ 54 ] and involved in the regulation of proapolipoprotein (apo) AI (apoAI) posttranslational processing [ 55 ]: apoAI binds β -amyloid peptide, a major protein in the brain associated with Alzheimer's and Parkinson's diseases, thus preventing Abeta-induced neurotoxicity [ 76 ].…”