Jia Xin, Li Ziyang, Shen Xiafeng, Zhang Yu, Zhang Li, Zhang Ling
Department of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China.
Department of Rehabilitation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
Neural Regen Res. 2023 Nov;18(11):2535-2544. doi: 10.4103/1673-5374.371373.
Physical exercise effectively alleviates chronic pain associated with complex regional pain syndrome type-I. However, the mechanism of exercise-induced analgesia has not been clarified. Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system. However, whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-I has not been demonstrated. In the present study, a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-I and subjected to an intervention involving swimming at different intensities. Chronic pain was reduced only in mice that engaged in high-intensity swimming. The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain, while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23. Finally, shRNA-mediated silencing of chemerin receptor 23 in the spinal cord reversed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammatory polarization of microglia in the dorsal horn of the spinal cord. These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.
体育锻炼能有效缓解与I型复杂性区域疼痛综合征相关的慢性疼痛。然而，运动诱导镇痛的机制尚未阐明。最近的研究表明，专门的促消退脂质介质RvE1通过与神经系统中的chemokine样受体1（CMKLR1）结合来促进病理性疼痛的缓解。然而，RvE1-CMKLR1轴是否参与I型复杂性区域疼痛综合征的运动诱导镇痛尚未得到证实。在本研究中，建立了慢性缺血后疼痛小鼠模型以模拟I型复杂性区域疼痛综合征，并对其进行不同强度游泳的干预。只有进行高强度游泳的小鼠的慢性疼痛得到减轻。慢性疼痛小鼠脊髓中的RvE1-CMKLR1轴明显下调，而高强度游泳恢复了RvE1和CMKLR1的表达。最后，脊髓中CMKLR1的短发夹RNA（shRNA）介导的沉默逆转了高强度游泳运动对慢性缺血后疼痛的镇痛作用以及脊髓背角小胶质细胞的抗炎极化。这些发现表明，高强度游泳可通过脊髓中内源性RvE1-CMKLR1轴减轻慢性疼痛。
