Chen Xuejiao, Chen Yan, Shu Runzhe, Lu Shunyuan, Gu Ming-Min, Shen Chunling, Wang Zhugang, Cui Xiaofang
Institute of Neuroscience and Brain science, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, China.
State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Hereditas. 2025 Mar 3;162(1):31. doi: 10.1186/s41065-025-00377-9.
Mas-related G protein-coupled receptors (Mrgs) are a subset of GPCRs linked to pain modulation. MrgF was identified as an orphan Mrg whose function and ligand remain unclear. In this study, in addition to its expression in the dorsal root ganglia (DRG), the primary afferent center that transmits pain, we identified dense expression of MrgF, particularly concentrated in the Purkinje cell layer of the mouse cerebellum. Given the the important role of Purkinje neurons in both motor modulation and non-motor modulation, including pain processing, we established a MrgF knockout mouse (MrgF) model and performed a battery of behavioral tests to explore motor performance and assess pain-associated responses. MrgF mice exhibited no disturbances in coordination and motor balance during the rotarod, pole, balance beam, and treadmill tests, and normal cerebellar histology was retained. In hot plate assays, MrgF mice displayed reduced pain-related behavioral responses to thermal stimuli, although no significance differences were found in tail flick assays between MrgF and wild-type (wt) mice. Moreover, in formalin tests, MrgF mice also showed decreased chemical-induced nociception. This was accompanied by a downregulation in the expression levels of genes associated with nociceptive modulation, such as c-fos, Runx1, Nav1.7, Nav1.8, and Nav1.9, within the DRG of MrgF mice. Taken together, our findings suggest that MrgF may play a significant role in modulating pain sensitivity, thereby advancing the understanding of the functional characteristics of the Mrgs family.
Mas相关G蛋白偶联受体（Mrgs）是与疼痛调节相关的G蛋白偶联受体的一个子集。MrgF被鉴定为一个孤儿Mrg，其功能和配体尚不清楚。在本研究中，除了在背根神经节（DRG）（传递疼痛的初级传入中心）中表达外，我们还发现MrgF在小鼠小脑的浦肯野细胞层中密集表达。鉴于浦肯野神经元在运动调节和非运动调节（包括疼痛处理）中都起着重要作用，我们建立了MrgF基因敲除小鼠（MrgF）模型，并进行了一系列行为测试，以探索运动表现并评估疼痛相关反应。在转棒试验、爬杆试验、平衡木试验和跑步机试验中，MrgF小鼠在协调和运动平衡方面没有表现出干扰，并且保留了正常的小脑组织学。在热板试验中，MrgF小鼠对热刺激的疼痛相关行为反应有所减少，尽管在甩尾试验中MrgF小鼠和野生型（wt）小鼠之间未发现显著差异。此外，在福尔马林试验中，MrgF小鼠也表现出化学诱导的伤害感受降低。这伴随着MrgF小鼠DRG内与伤害感受调节相关的基因（如c-fos、Runx-1、Nav1.7、Nav1.8和Nav1.9）表达水平的下调。综上所述，我们的研究结果表明，MrgF可能在调节疼痛敏感性方面发挥重要作用，从而增进对Mrgs家族功能特征的理解。
