Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (8): 1841-1846.doi: 10.4103/1673-5374.361533

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Exercise combined with administration of adipose-derived stem cells ameliorates neuropathic pain after spinal cord injury

Xing Cheng1, #, Gu-Ping Mao2, #, Wen-Jie Hu3, #, Zheng-Ran Yu1, 4, #, Yi-Yang Xu2, Wei Chen5, Xiang Li1,  Xiao-Lin Zeng1, Wen-Wu Zhang1, Jie-Wen Chen1, Yong Wan1, *, Le Wang1, *   

  1. 1Department of Spine Surgery, Orthopedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou, Guandong Province, China; 2Department of Joint Surgery and Sport Medicine, Orthopedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou, Guandong Province, China; 3Department of Rehabilitation Medicine, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guandong Province, China; 4Department of Spine Surgery, Orthopedics Center of Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guandong Province, China; 5State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guandong Province, China
  • Online:2023-08-15 Published:2023-02-24
  • Contact: Yong Wan, PhD, wanyong@mail.sysu.edu.cn; Le Wang, PhD, wangle3@mail.sysu.edu.cn.
  • Supported by:
    This study was supported in part by the National Natural Science Foundation of China, Nos. 81971151 (to YW), 82201360 (to XC), 82102583 (to LW), and 82202739 (to GPM); China Postdoctoral Science Foundation, Nos. YJ20210208 and 2022M713592; Guangdong Basic and Applied Basic Research Foundation, China, No. 2021A1515110188 (to XC); the Natural Science Foundation of Guangdong Province, China, No. 2020A1515010306 (to LW); the Science and Technology Program of Guangzhou, China, No. 202102020040 (to LW).

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Abstract: Experimental studies have shown that exercise and human adipose-derived stem cells (ADSCs) play positive roles in spinal cord injury (SCI). However, whether ADSCs and/or exercise have a positive effect on SCI-induced neuropathic pain is still unclear. Thus, there is a need to explore the effects of exercise combined with administration of ADSCs on neuropathic pain after SCI. In this study, a thoracic 11 (T11) SCI contusion model was established in adult C57BL/6 mice. Exercise was initiated from 7 days post-injury and continued to 28 days post-injury, and approximately 1 × 105 ADSCs were transplanted into the T11 spinal cord lesion site immediately after SCI. Motor function and neuropathic pain-related behaviors were assessed weekly using the Basso Mouse Scale, von Frey filament test, Hargreaves method, and cold plate test. Histological studies (Eriochrome cyanine staining and immunohistochemistry) were performed at the end of the experiment (28 days post-injury). Exercise combined with administration of ADSCs partially improved early motor function (7, 14, and 21 days post-injury), mechanical allodynia, mechanical hypoalgesia, thermal hyperalgesia, and thermal hypoalgesia. Administration of ADSCs reduced white and gray matter loss at the lesion site. In addition, fewer microglia and astrocytes (as identified by expression of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, respectively) were present in the lumbar dorsal horn in the SCI + ADSCs and SCI + exercise + ADSCs groups compared with the sham group. Our findings suggest that exercise combined with administration of ADSCs is beneficial for the early recovery of motor function and could partially ameliorate SCI-induced neuropathic pain. 

Key words: adipose-derived stem cells, allodynia, exercise, glial fibrillary acidic protein, hyperalgesia, hypoalgesia, ionized calcium-binding adapter molecule 1, motor function, spinal cord injury