ArticlePain2014
MrgC agonism at central terminals of primary sensory neurons inhibits neuropathic pain.
Article in Pain, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- An orally bioavailable MrgprX1-positive allosteric modulator alleviates certain neuropathic pain-related behaviors in humanized mice.Science translational medicine · 2025Article
- BAM8-22 targets spinal MrgC receptors to modulate UPRFrontiers in pharmacology · 2025Article
- Berbamine Reduces Chloroquine-Induced Itch in Mice through Inhibition of MrgprX1.International journal of molecular sciences · 2022Article
- Potential Molecular Targets for Treating Neuropathic Orofacial Pain Based on Current Findings in Animal Models.International journal of molecular sciences · 2021Review
- The signaling pathway and polymorphisms of Mrgprs.Neuroscience letters · 2021Review
- Activation of µ-δ opioid receptor heteromers inhibits neuropathic pain behavior in rodents.Pain · 2020Article
- The Ubiquitination of Spinal MrgC Alleviates Bone Cancer Pain and Reduces Intracellular Calcium Concentration in Spinal Neurons in Mice.Neurochemical research · 2019Article
- Discovery of Benzamidine- and 1-Aminoisoquinoline-Based Human MAS-Related G-Protein-Coupled Receptor X1 (MRGPRX1) Agonists.Journal of medicinal chemistry · 2019Article
- Oligomerization of MrgC11 and μ-opioid receptors in sensory neurons enhances morphine analgesia.Science signaling · 2018Article
- Peripherally Acting μ-Opioid Receptor Agonists Attenuate Ongoing Pain-associated Behavior and Spontaneous Neuronal Activity after Nerve Injury in Rats.Anesthesiology · 2018Article
- Involvement of MrgprC in Electroacupuncture Analgesia for Attenuating CFA-Induced Thermal Hyperalgesia by Suppressing the TRPV1 Pathway.Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Activation of Peripheral μ-opioid Receptors by Dermorphin [D-Arg2, Lys4] (1-4) Amide Leads to Modality-preferred Inhibition of Neuropathic Pain.Anesthesiology · 2016Article
- Activation of spinal MrgC-Gi-NR2B-nNOS signaling pathway by Mas oncogene-related gene C receptor agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice.American journal of translational research · 2016Article
- The inhibition of high-voltage-activated calcium current by activation of MrgC11 involves phospholipase C-dependent mechanisms.Neuroscience · 2015Article
- Article
- Discovery and characterization of 2-(cyclopropanesulfonamido)-N-(2-ethoxyphenyl)benzamide, ML382: a potent and selective positive allosteric modulator of MrgX1.ChemMedChem · 2015Article
- Mas-related G-protein-coupled receptor c agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice.International journal of clinical and experimental medicine · 2015Article
- Peptidomimetics of Arg-Phe-NH2 as small molecule agonists of Mas-related gene C (MrgC) receptors.Bioorganic & medicinal chemistry · 2014Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic neuropathic pain is often refractory to current pharmacotherapies. The rodent Mas-related G-protein-coupled receptor subtype C (MrgC) shares substantial homogeneity with its human homologue, MrgX1, and is located specifically in small-diameter dorsal root ganglion neurons. However, evidence regarding the role of MrgC in chronic pain conditions has been disparate and inconsistent. Accordingly, the therapeutic value of MrgX1 as a target for pain treatment in humans remains uncertain. Here, we found that intrathecal injection of BAM8-22 (a 15-amino acid peptide MrgC agonist) and JHU58 (a novel dipeptide MrgC agonist) inhibited both mechanical and heat hypersensitivity in rats after an L5 spinal nerve ligation (SNL). Intrathecal JHU58-induced pain inhibition was dose dependent in SNL rats. Importantly, drug efficacy was lost in Mrg-cluster gene knockout (Mrg KO) mice and was blocked by gene silencing with intrathecal MrgC siRNA and by a selective MrgC receptor antagonist in SNL rats, suggesting that the drug action is MrgC dependent. Further, in a mouse model of trigeminal neuropathic pain, microinjection of JHU58 into ipsilateral subnucleus caudalis inhibited mechanical hypersensitivity in wild-type but not Mrg KO mice. Finally, JHU58 attenuated the miniature excitatory postsynaptic currents frequency both in medullary dorsal horn neurons of mice after trigeminal nerve injury and in lumbar spinal dorsal horn neurons of mice after SNL. We provide multiple lines of evidence that MrgC agonism at spinal but not peripheral sites may constitute a novel pain inhibitory mechanism that involves inhibition of peripheral excitatory inputs onto postsynaptic dorsal horn neurons in different rodent models of neuropathic pain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.