Temporal changes in MrgC expression after spinal nerve injury

Abstract

Mas-related G-protein-coupled receptor subtype C (MrgC) may play an important role in pain sensation. However, the distribution of MrgC receptors in different subpopulations of rodent dorsal root ganglion (DRG) neurons has not been clearly demonstrated owing to a lack of MrgC-selectively antibody. It is also unclear whether peripheral nerve injury induces different time-dependent changes in MrgC expression in injured and uninjured DRG neurons. Here we showed that MrgC immunoreactivity is distributed in both IB4-positive (non-peptidergic) and calcitonin gene-related peptide-positive (peptidergic) DRG neurons in mice and rats. Importantly, the MrgC mRNA level and MrgC immunoreactivity were both decreased in the injured L5 DRG compared to corresponding levels in the contralateral (uninjured) DRG in rats on days 14 and 30 after an L5 spinal nerve ligation. In contrast, mRNA and protein levels of MrgC were increased in the adjacent uninjured L4 DRG. Thus, nerve injury may induce temporal changes in MrgC expression that differ between injured and uninjured DRG neurons. In animal behavior tests, chronic constriction injury of the sciatic nerve induced mechanical pain hypersensitivity in wild-type mice and Mrg-clusterΔ−/− mice (Mrg KO). However, the duration of mechanical hypersensitivity was longer in the Mrg KO mice than in their wild-type littermates, indicating that activation of Mrgs may constitute an endogenous mechanism that inhibits the maintenance of neuropathic pain. These findings extend our knowledge about the distribution of MrgC in rodent DRG neurons and the regulation of its expression by nerve injury.

Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain

“…The level of BAM22 is upregulated in the spinal cord of MrgprX1 mice after tissue inflammation and nerve injury. Up-regulation of BAM22 and MRGPRC receptor has also been reported in rodent models of inflammatory and neuropathic pain (14,51,52). Accordingly, enhanced endogenous pain inhibition mediated by MRGPRC and MRGPRX1 in rodents and humans may parallel endogenous pain inhibition of opioid receptors and converge on BAM peptide to suppress chronic pain (53,54).…”

“…application attenuates inflammatory and neuropathic pain-related behavior in rodent models (6,21). In contrast, Mrgpr-clusterΔ −/− (Mrgpr −/− ) mice, which have a deletion of 12 Mrgprs, including MrgprA3 and MrgprC11, display enhanced inflammatory (21) and prolonged neuropathic pain (14). These data suggest that MRGPRC at central terminals of primary sensory neurons may function as an endogenous pain inhibitor mechanism in rodents.…”

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

“…These receptors are selectively expressed on small diameter neurons and contribute to processing of pain and itch responses (Dong et al, 2001;Han et al, 2013). Several lines of evidence from wild-type or Mrg knockout mice indicate that these receptors are upregulated in response to sciatic nerve injury and provide an endogenous mechanism for the inhibition of mechanical, thermal, and inflammatory pain hypersensitivity (Guan et al, 2010;He et al, 2014). MrgC receptor-dependent mechanisms of analgesia are not entirely clear but may enhance m-opioid receptor Ga i/o signaling (Wang et al, 2013).…”

Activation of Mas Oncogene-Related G Protein–Coupled Receptors Inhibits Neurochemical Alterations in the Spinal Dorsal Horn and Dorsal Root Ganglia Associated with Inflammatory Pain in Rats

“…These results can be interpreted as a modulation of the inflammation-associated increase in the expression and/or release of CGRP, nNOS, and excitatory amino acids by MrgC receptors. This suggestion was supported by the findings showing the colocalization of MrgC receptors with CGRP (He et al, 2014a) and nNOS (Jiang et al, 2013) in DRG neurons and the attenuation of a miniature excitatory postsynaptic current in spinal dorsal horn neurons by MrgC receptors (He et al, 2014b) The MrgC receptors are upregulated in the conditions of inflammatory (Jiang et al, 2013) and neuropathic (He et al, 2014a) pain. Previous studies have shown that activation of MrgC receptors modulates inflammatory pain (Chen et al, 2006;Jiang et al, 2013) and does not influence physiologic pain (Cai et al, 2007;Guan et al, 2010).…”

“…Mrg receptors, also known as sensory neuron-specific receptors (Lembo et al, 2002), are synthesized in DRG and trigeminal ganglia (Dong et al, 2001) and also found in the central terminals of primary afferents (He et al, 2014a;Huang et al, 2014). Mrg receptors are divided into eight subtypes (MrgA-MrgH) in rodents (Dong et al, 2001) and seven subtypes (MrgX1-MrgX7) in humans (Dong et al, 2001;Choi and Lahn, 2003).…”