Analysis Of Risk Factors And Optimization Of RTMS Strategies For Neuropathic Pain After Spinal Cord Injury

BackgroundNeuropathic pain after spinal cord injury(SCI-NP)is a common and miserable pain to deal with.It has significantly negative influences on the quality of life by affecting physical function,mood,employment and social activities.The mechanisms and risk factors of SCI-NP remain obscure,which lead to a big challenge in SCI-NP prevention and management.The existing treatments for SCI-NP remains unsatisfactory.Although drugs have been recommended as the main treatment of SCI-NP,whereas only about 1/3 patients receive pain relief,and some patients have no choice but to stop the drugs because of the severe side effects.As a noninvasive brain stimulation(NIBS),repetitive transcranial magnetic stimulation(r TMS)is widely used in clinic at present,which has the advantages of safety and reliability.Accumulated researches have demonstrated that r TMS can relieve pain in patients with SCI-NP.However,r TMS is not effective for SCI-NP in all patients,and some studies showed that r TMS to be no more effective than the sham stimulation.This may be related to the lack of sessions or different targets of r TMS.Therefore,further researches are urgently needed on the optimal target of r TMS for SCI-NP and its potential mechanism for pain relief.MethodsPart Ⅰ:This part of the study was a retrospective case-control study.The subjects were 115 patients with SCI which admitted to the Department of Rehabilitation Medicine,Xijing hospital,Air Force Medical University from January 2018 to December 2021.They were divided into NP group(53 cases)and non-NP group(62 cases).The age,gender,SCI duration,education level,occupation,cause of injury,spinal fracture,injury level,injury degree,and complications(diabetes,hypertension,anemia,venous thrombosis,pressure sores,urinary tract infection and hypoalbuminemia)were analyzed respectively.The t-test and chi-square test were used to distinguish the differences of the above risk factors between the two groups,and to screen out the risk factors of SCI-NP,multivariate logistic regression analysis was applied.The specific type of NP,time of NP occurrence,pain location,pain characters and analgesics were further illustrated to provide ideas for the prevention and treatment of SCI-NP in clinical settings.Part Ⅱ:This part of the study was a prospective,single-center,double-blind,randomized and sham controlled clinical trial.A total of 46 patients who were hospitalized and diagnosed with SCI-NP in the Department of Rehabilitation Medicine,Xijing hospital,Air Force Medical University from June 2021 to December 2022 were recruited as subjects for the study.And according to different stimulation target: primary motor cortex(M1)and premotor cortex(PMC),they were randomly divided into three groups,M1+PMC group,M1 group and Sham group.On the basis of routine rehabilitation,the patients in the three groups were treated with high frequency(10 Hz)r TMS in the M1+PMC,sham stimulation in the PMC + high frequency r TMS in the M1 and sham stimulation in the M1+PMC,respectively.The Numerical Rating Scale(NRS)and the Mc Gill Pain Questionnaire-2(SFMPQ2)were assessed before the first treatment,and on day 1,week 1,2,4 and 6.The functional near-infrared spectroscopy(f NIRS)tests were performed before the first treatment,2 and 4 weeks after the first r TMS or sham treatment.The objection of the study is to clarify whether the M1+PMC combined r TMS protocol has a therapeutic advantage by comparing the difference of pain relief effect between the M1+PMC group and M1 group,and to further explore the cortical activity changes by comparing the changes of the average oxyhemoglobin(Hb O)concentration in the corresponding cortices of each group,to provide a theoretical basis for the optimization of the r TMS treatment strategy of SCI-NP.ResultsPart Ⅰ:1.The incidence of SCI-NP was high,and nearly half(45.22%)of the SCI patients will develop into SCI-NP within one year after injury.The features of NP mainly include tingling(33.96%),numbness(26.42%),hot-burning(22.64%),etc.Some patients may combine one or more different NP features.2.Female(OR = 3.210,95% CI 1.198-8.604,P = 0.020)and venous thrombosis(OR= 4.813,95% CI 1.874-12.363,P = 0.001)are independent risk factors for the occurrence of NP.Part Ⅱ:1.Routine treatment and combined with high frequency r TMS on M1 or M1+PMC can relieve NP symptoms in different degrees,while the analgesic effect in M1+PMC group is faster and superior than that in M1 group,indicating the effects of multi-target coordination and time accumulation of r TMS.2.After 4 weeks of r TMS,the activation of left premotor cortex(LPMC)and left primary motor cortex(LM1)in M1+PMC group and M1 group were significantly suppressed.Conclusions1.After SCI,female and patients with venous thrombosis are more likely to develop into NP.Patients diagnosed with SCI-NP should be given timely,reasonable and adequate treatment so as not to develop into intractable NP.2.The analgesic effect of M1+PMC high frequency r TMS on SCI-NP is superior than that of M1.3.The analgesic effect of high frequency r TMS may be related to the amelioration of over-activation of M1 and PMC.