Xinyu Liu,1,2,* Chunqiu Dai,1,3,* Ming Gao,1,* Xiaodong Lin,1 Xiao Xi,1 Xiangbo Wu,1 Guiqing Cheng,1 Tao Han,1 Qiaozhen Li,1 Yixing Lu,1 Xiaolong Sun,1 Hua Yuan1 

1Department of Rehabilitation Medicine, The First Affiliated Hospital, Air Force Medical University (Fourth Military Medical University) of Chinese People’s Liberation Army, Xi’an, Shaanxi, People’s Republic of China; 2Department of Rehabilitation Medicine, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Lanzhou, Gansu, People’s Republic of China; 3Lintong Rehabilitation and Convalescent Centre, Xi’an, Shaanxi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hua Yuan; Xiaolong sun, Department of Rehabilitation Medicine, The First Affiliated Hospital, Air Force Medical University (Fourth Military Medical University) of Chinese People’s Liberation Army, No. 127, Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel/Fax +86-29-84775437 ; +86-29-84775439, Email yuanhua@fmmu.edu.cn; xlsun@fmmu.edu.cn

Purpose: Neuropathic pain (NP) is a major and debilitating complication of spinal cord injury (SCI), frequently occurring bilaterally below the injury level. Repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) is suggested as a treatment for NP following SCI (SCI-NP). However, the specific changes in corticospinal excitability (CSE) within the bilateral M1 remain unclear, hindering the development of optimized rTMS parameters for SCI-NP.
Patients and Methods: This retrospective study analyzed data from 625 SCI patients and 131 healthy controls. Motor-evoked potential (MEP) was used to assess CSE in the bilateral M1 hand areas. The hemispheric asymmetry of bilateral M1 CSE was measured by calculating the natural logarithm of the MEP amplitude ratio between the dominant hemisphere (DH) and non-dominant hemisphere (NDH), expressed as ln(DH/NDH amplitude). The study utilized correlation analysis and multiple linear regression to examine the associations between hemispheric CSE asymmetry and the course, severity, and emotional disturbances of NP.
Results: SCI patients experiencing NP exhibited lower MEP amplitude than those without NP in bilateral M1 hand areas, with a more pronounced decrease in NDH. Hemispheric CSE asymmetry was found to be elevated and positively correlated with NP course (r=0.213, P=0.034), severity (r=0.317, P=0.004), and emotional disturbances (r=0.294, P=0.009). Notably, hemispheric CSE asymmetry was independently associated with NP severity and emotional disturbances, particularly in younger individuals (under 52 years), those with traumatic injuries, and those with non-cervical SCI.
Conclusion: Hemispheric CSE asymmetry shows potential as a biomarker for assessing SCI-NP severity and emotional disturbances in SCI patients. High-frequency rTMS targeting bilateral M1 hand areas may provide improved analgesic effects. This finding could enhance neuropathic pain assessment and guide rTMS optimization, potentially improving the quality of life for individuals with SCI.

Keywords: spinal cord injury, neuropathic pain, corticospinal excitability, MEP, hemispheric CSE asymmetry, rTMS