Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (7): 3092-3102.doi: 10.4103/NRR.NRR-D-24-00912

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Trans-spinal magnetic stimulation upregulates microglial SOCS3 to attenuate neuroinflammation in chronic constriction injury–induced neuropathic pain

Qi Wu1, 2, #, Xingjun Xu3, #, Chenyuan Zhai4, #, Jili Cai2, Zun Wang2, Lu Fang2, Yu Wang2, Yilun Qian2, Manyu Dong2, Liang Hu5, *, Tong Wang2, *, Ying Shen2, *, Wentao Liu5, *   

  1. 1Department of Rehabilitation, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, Hunan Province, China; 
    2Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, Jiangsu Province, China;  3Department of Rehabilitation, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China;  4Department of Rehabilitation Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu Province, China;  5Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province, China
  • Online:2026-07-15 Published:2026-04-01
  • Contact: Liang Hu, PhD, lianghu@njmu.edu.cn; Tong Wang, MD, PhD, wangtong60621@163.com; Ying Shen, MD, PhD, shenying@njmu.edu.cn; Wentao Liu, PhD, painresearch@njmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82302877 (to QW), 82172541 (to TW); the Natural Science Foundation of Hunan Province, No. 2023JJ30549 (to QW); and the Clinical Medical Technology Innovation Guidance Project of Hunan Provincial Science and Technology Department, No. 2021SK51815 (to QW).

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Abstract: Current treatments for neuropathic pain are suboptimal, necessitating the search for more effective therapeutics. Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects, and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models. Here, we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta (CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase (AMPK)/suppressor of cytokine signaling-3 (SOCS3) signaling in microglia. Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation. Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia, which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain, thereby suppressing neuroinflammation. The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia. The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia. This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury. 
 

Key words: CaMKKβ/AMPK/SOCS3 signaling, chronic constriction injury, mechanical pain sensitivity, microglia, neuropathic pain, neuroinflammation, nuclear factor-κB p65, repetitive trans-spinal magnetic stimulation, STAT3