Ma Zhangyu, Wan Qianqian, Qin Wenpin, Qin Wen, Yan Janfei, Zhu Yina, Wang Yuzhu, Ma Yuxuan, Wan Meichen, Han Xiaoxiao, Zhao Haoyan, Hou Yuxuan, Tay Franklin R, Niu Lina, Jiao Kai
Department of Stomatology, Tangdu Hospital & State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
Int J Oral Sci. 2025 Jan 7;17(1):3. doi: 10.1038/s41368-024-00336-6.
Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
颞下颌关节骨关节炎（TMJ - OA）是一种常见疾病，常伴有疼痛，严重影响患者的身心健康。骨软骨交界处的神经支配异常被认为是关节疼痛的主要根源，而介导疼痛的具体机制尚不清楚。为了探究TMJ - OA疼痛的潜在机制，我们使用异常关节负荷模型诱导TMJ - OA疼痛。我们发现，在TMJ - OA的发展过程中，软骨下骨交感神经支配的增加先于感觉神经。此外，这两种神经在空间上紧密相关。另外，研究发现交感神经信号的激活会促进小鼠骨关节炎疼痛，而阻断这些信号可有效减轻疼痛。体外实验也证实，交感神经元释放的去甲肾上腺素会促进感觉神经元的激活和轴突生长。此外，我们还发现，通过释放去甲肾上腺素，软骨下骨局部交感神经与其他疼痛调节因子协同调节局部感觉神经的生长和激活。本研究确定了局部交感神经在介导TMJ - OA疼痛中的作用。它揭示了骨软骨交界处神经支配异常和外周神经区域间相互作用的新机制，为治疗TMJ - OA疼痛提供了潜在靶点。
