ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Facilitation of MrgprD by TRP-A1 promotes neuropathic pain.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Identification and validation of MicroRNA-mRNA Networks in Dorsal Root Ganglia after Peripheral Nerve Injury.International journal of medical sciences · 2022Pooled it
- Pirt promotes substance P release in cancer-induced bone pain.Pain reports · 2026Article
- Tetrahydropalmatine alleviates cancer induced bone pain by inhibiting TRPV1-SP-mediated macrophage recruitment and promoting M2 polarization.Chinese medicine · 2026Article
- From neuroimmune circuits to targeted therapy of chronic pruritus.Pharmacological reviews · 2026Review
- Mas-Related G-Protein-Coupled Receptors: Emerging Roles in Neuropathic Pain.Biomolecules · 2026Review
- Dual function of MrgprB2 receptor-dependent neural immune axis in chronic pain.Journal of advanced research · 2025Article
- Unraveling the neuroimmune mechanisms in cancer-induced bone pain: New horizons for therapeutic intervention of the two-phase paradigm.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The μ-opioid receptor differentiates two distinct human nociceptive populations relevant to clinical pain.Cell reports. Medicine · 2024Article
- Atopic dermatitis in early life and pain at 10 years of age: An exploratory study.European journal of pediatrics · 2024Article
- Transient Receptor Potential Channels: Multiple Modulators of Peripheral Neuropathic Pain in Several Rodent Models.Neurochemical research · 2024Review
- Potential Therapeutic Effects of Short-Chain Fatty Acids on Chronic Pain.Current neuropharmacology · 2024Review
- The role of nociceptive neurons in allergic rhinitis.Frontiers in immunology · 2024Review
- Article
- IQGAP1 promotes chronic pain by regulating the trafficking and sensitization of TRPA1 channels.Brain : a journal of neurology · 2023Article
- Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia.iScience · 2023Article
- The structure, function, and pharmacology of MRGPRs.Trends in pharmacological sciences · 2023Review
- Sensory innervation of the lumbar 5/6 intervertebral disk in mice.Frontiers in neurology · 2023Article
- The translational revolution of itch.Neuron · 2022Review
- Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM.Communications biology · 2022Article
- Global analyses of mRNA expression in human sensory neurons reveal eIF5A as a conserved target for inflammatory pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
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Authors and funding
18 authors at 7 institutions in 2 countries.
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Abstract
Neuropathic pain remains a therapeutic challenge because of its complicated mechanisms. Mas-related GPCR D (MrgprD) is specifically expressed in small-diameter, nociceptive neurons of dorsal root ganglia (DRGs) and is implicated in pain modulation. However, the underlying mechanism of MrgprD involved in neuropathic pain remains elusive. In this study, we used behavioral experiments and physiologic examination methods to investigate the role of MrgprD in chronic constriction injury (CCI)-induced neuropathic pain. We found that MrgprD is necessary for the initiation of mechanical hypersensitivity and cold allodynia, but not for heat allodynia. Moreover, we demonstrated that transient receptor potential cation channel (TRP)-A1 was the ion channel downstream of MrgprD, and the β-alanine-induced calcium signal was attributed mostly to TRP-A1 function. We further showed that PKA serves as a downstream mediator of β-alanine-activated MrgprD signaling to activate TRP-A1 in DRG neurons and in human embryonic kidney 293 cells, to coexpress MrgprD and TRP-A1 plasmids. Finally, we found that the β-alanine-induced pain behavior was increased, whereas the itching behavior was unchanged in CCI models compared with sham-injured animals. Knockout of TRPA1 also attenuated the β-alanine-induced pain behavior in CCI models. In conclusion, MrgprD is essential in cold allodynia in CCI-induced neuropathic pain through the PKA-TRP-A1 pathway. TRP-A1 facilitates MrgprD to development of neuropathic pain. Our findings reveal a novel mechanism of neuropathic pain formation and highlight MrgprD as a promising drug target for the treatment of neuropathic pain.-Wang, C., Gu, L., Ruan, Y., Geng, X., Xu, M., Yang, N., Yu, L., Jiang, Y., Zhu, C., Yang, Y., Zhou, Y., Guan, X., Luo, W., Liu, Q., Dong, X., Yu, G., Lan, L., Tang, Z. Facilitation of MrgprD by TRP-A1 promotes neuropathic pain.
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