Randomized Controlled Trial of the Effects of Repetitive Transcranial Magnetic Stimulation and Mirror Therapy on Phantom Limb Pain in Amputees
-
摘要:目的 探讨重复经颅磁刺激(repetitive transcranial magnetic stimulation, rTMS)对截肢患者幻肢痛的影响,并与镜像疗法(mirror therapy, MT)进行比较。方法 本研究采用随机对照试验设计,评估者盲,受试者和治疗师非盲。通过计算机生成随机数字表,将受试者随机分配到rTMS组或MT组。2018年6月–2020年12月期间,从四川大学华西医院康复医学中心的45例截肢患者中筛查出符合研究标准的30例纳入研究。4例中途退出,最终26例完成规定治疗和评估(rTMS组12例,MT组14例)。rTMS组在常规康复治疗的基础上,还接受为期2周的重复经颅磁刺激(1 Hz,15 min,5 d/周),MT组在常规康复治疗的基础上,还接受为期2周的镜像疗法(肢体相应动作,15 min, 5 d/周)。结局指标为基础疼痛视觉模拟评分(visual analogue scale, VAS)和神经病理性疼痛四问(Douleur Neuropathique 4 questions, DN-4)。在治疗前(t0)、治疗结束后即刻(t1)、治疗结束后3个月(t2)对受试者进行疼痛评估。结果 26例患者平均年龄(39.73±12.64)岁,男性15例,女性11例。纳入的截肢患者对幻肢痛特征描述中,总体发生率最高的依次是麻刺感、刀割感、麻木感、放电感和灼烧感;两组间幻肢痛特征发生率差异无统计学意义(P>0.05)。两组基线可比,VAS和DN-4在t0差异无统计学意义(P>0.05)。两组患者t1、t2的VAS和DN-4较t0降低,差异均有统计学意义(P均<0.01);rTMS组患者t2的VAS和DN-4与t1相当,差异均无统计学意义(P>0.05);MT组患者t2的VAS和DN-4低于t1,差异均有统计学意义(P<0.05)。两组间治疗前后各时点VAS和DN-4疼痛差值差异均无统计学意义(P>0.05)。26例完成试验的患者在研究过程中未见头晕、头痛等异常。结论 rTMS对截肢患者幻肢痛有改善作用,但其改善作用与镜像疗法相当。Abstract:Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on phantom limb pain (PLP) in amputees, and to compare the therapeutic effect with that of mirror therapy (MT).Methods The study was designed as a randomized controlled trial. The evaluators were blinded, while the subjects and the therapists were unblinded. Subjects were randomly assigned to either the rTMS group or the MT group with a computer-generated random number table. From June 2018 to December 2020, from out of 45 amputee patients screened for the study, 30 who met the inclusion criteria were recruited for the study. All patients were recruited from the Rehabilitation Medicine Center, West China Hospital, Sichuan University. In the end, 4 patients withdrew from the study and 26 patients (12 in the rTMS group and 14 in the MT group) completed the prescribed treatment and evaluation. The rTMS group was given rTMS (1 Hz, 15 min, 5 d/week) for 2 weeks in addition to conventional rehabilitation therapy, while the MT group received MT (corresponding movements of limbs, 15 min, 5 d/week) for 2 weeks in addition to conventional rehabilitation therapy. PLP was evaluated by the Visual Analogue Scale (VAS) and Douleur Neuropathique 4 Questions (DN-4). Subjects were assessed before treatment (t0), immediately after the completion of the treatment (t1) and 3 months after the completion of the treatment (t2).Results The mean age of the 26 patients was 39.73±12.64. There were 15 males and 11 females. According to the reported description of the characteristics of the PLP by the patients, the characteristics with the highest incidence were tingling, stabbing, numbing, electric shocks and burning in descending order. There was no significant difference in the incidence of PLP characteristics between the two groups (P>0.05). The two groups had comparable baseline data, showing no significant difference in VAS and DN-4 between the two groups at t0 (P>0.05). At t1 and t2, the VAS and DN-4 scores were decreased from those of t0, showing statistically significant difference in both groups (P<0.01 for both scores). In the rTMS group, there was no significant difference between VAS and DN-4 scores at t1 and those at t2 (P>0.05). In the MT group, the VAS and DN-4 scores at t2 were significantly lower than those of t1 (P<0.05). There was no statistically significant difference between the rTMS group and MT group in the changes in pain measurements, i.e., VAS and DN-4 scores, before and after the intervention (P>0.05). The 26 patients who completed the experiment showed no dizziness, headache, or other abnormalities during the study.Conclusion The results of this study indicate that repetitive transcranial magnetic stimulation could improve PLP in amputees, and the improvement effect was comparable to that of mirror therapy.
-
幻肢痛(phantom limb pain, PLP)是截肢后常见的并发症,患者感到被截除的肢体依然存在幻肢感(phantom limb sensation, PLS),且伴有不同程度的烧灼痛、针刺痛、麻痛、痒痛、挤压痛等不同性质的疼痛[1-3]。在已往的研究中,PLP的发病率高达80%,大多发生在术后1个月内,但也可能在截肢数年后发生[4-6]。作为一种神经病理性疼痛,PLP的常规药物治疗效果不佳,且对截肢患者的日常生活、工作、情绪、生活质量等造成严重的影响[7-9]。
PLP的非药物治疗有神经阻滞、镜像疗法(mirror therapy, MT)、重复经颅磁刺激(repetitive transcranial magnetic stimulation, rTMS)、经皮神经电刺激、认知行为疗法、感觉识别训练、针灸、分级运动想象等[10]。其中,MT基于视觉反馈刺激,利用完整肢体的随意运动在镜中产生的映像使患者产生幻肢正常运动的错觉,进而改善截肢后大脑皮质重组[11]。作为康复治疗师用来改善PLP的常用手段,已有大量临床研究验证了MT改善PLP的有效性[10, 12]。作为新兴的非侵入性神经调控技术,rTMS通过电-磁转化直接穿透颅骨而作用于局部大脑皮层并形成感应电流,从而调节大脑局部皮层及相关远隔部位兴奋性[13]。有学者认为rTMS对幻肢痛可能有效,并有少量个案报道及临床研究结果表明其正向作用[14-15]。本研究旨在通过随机对照试验设计,比较rTMS与MT治疗PLP的临床疗效,为后续PLP临床实践及机制探讨提供参考。
1. 对象与方法
1.1 研究对象及标准
截肢患者于2018年6月–2020年12月期间从四川大学华西医院康复医学中心病房招募,要求所有受试者在进入研究前签署知情同意。该研究已通过四川大学华西医院生物医学伦理委员会批准(批准号2016/311),在中国临床试验注册中心注册(注册号ChiCTR1800015580)。
1.1.1 纳入标准
①外伤后截肢患者;②伴有PLP,服用药物1周后基础疼痛视觉模拟评分(visual analogue scale, VAS)仍≥3分;③年龄≥18岁;④受试者无严重认知障碍,能理解和执行治疗人员的简单指令。
1.1.2 排除标准
①复杂区域疼痛综合征患者;②残端破溃,严重感染者;③妊娠女性;④伴有因糖尿病周围神经病变、颈腰椎病等引起的疼痛;⑤有出血倾向的患者:严重心脏病、严重高血压及严重的心、肝、肺、肾衰竭的患者;⑥使用植入式电子装置的患者;⑦颅内感染或颅内肿瘤患者;⑧有颅内血管金属支架植入者。
1.1.3 中止标准
①出现严重疾病并发症,如肺栓塞、严重肺部感染、毒血症等不能完成MT或rTMS治疗;②rTMS治疗过程中发生癫痫,严重头晕、头痛等;③MT治疗过程中发生严重头痛、头晕、恶心、呕吐等。
1.1.4 剔除和脱落标准
①依从性差,不按医嘱治疗者;②研究过程中自行退出研究者;③随访过程中因各种原因失访者。
1.2 试验设计
本研究采用随机对照试验设计,采取评估者盲,受试者和治疗师非盲。样本量估算参照AHMED等[16]的研究结果,该研究使用VAS评估rTMS对截肢后PLP的改善。采用G*power 3.1软件计算样本量,设α=0.05,检验效能β=0.2,备择假设为双侧,两组样本量比值1∶1。经计算,得出每组所需样本13例,预计10%的脱落率,每组需15例,共计划纳入30例。由计算机生成随机数字表,制作随机卡,有序地放在密封、不透明的信封中,由非课题组成员负责将受试者随机分配到rTMS组或MT组。
对2018年6月–2020年12月期间在四川大学华西医院康复医学中心住院的45例截肢患者进行筛选,其30例受试者符合研究标准,研究过程中,rTMS组有3例在治疗过程中退出(1例在一次治疗后自述头痛要求退出,1例在2次治疗后因病情变化转科,1例在1次治疗后要求退出未述缘由),退出比例为20%,MT组有1例在治疗过程中退出(该例在第1次治疗时出现头痛、恶心,要求退出),退出比例为6.67%,最终26例(rTMS组12例,MT组14例)受试者完成所有治疗并接受随访,结果纳入统计分析。
1.3 分组干预方法
rTMS组和MT组均接受常规截肢后康复治疗,包括肢体肌力及活动度训练,日常生活活动能力训练,残端护理及塑形等。此外,rTMS组还接受rTMS,每次15 min,每天1次,每周5 d,共2周;MT组还接受镜像治疗,每次15 min,每天1次,每周5 d,共2周。
1.3.1 rTMS
患者卧位,采用依瑞德CCY-1型经颅磁刺激治疗仪,8字形线圈,线圈与头皮相切,刺激频率1 Hz,刺激强度为80%静息运动阈值,连续刺激900 s,每次治疗共计900个刺激脉冲。刺激部位为截肢侧对侧大脑运动区(幻肢对应M1区),具体刺激部位如下:①膝下截肢、膝上截肢和膝离断患者的刺激部位为患侧下肢对应M1区;②肘下截肢、肘上截肢和肘离断患者刺激部位为患侧上肢对应M1区;③双侧下肢截肢患者刺激部位为M1区顶部;④双侧上肢截肢患者刺激部位为两侧上肢分别对应的M1区,进行两侧的先后刺激。
1.3.2 MT
患者坐在椅子上,双侧下肢或上肢裸露,在两腿或两臂之间放置镜子(宽×高:上肢20 cm×30 cm;下肢60 cm×200 cm),调试镜子位置,使患者能在镜子中看到健侧肢体,截肢侧隐藏于镜子后面。嘱患者健侧肢体主动运动,并集中精力观察镜子中肢体的姿势及动作映像。具体动作如下:①膝下截肢者,行踝背屈最大角度到跖屈最大角度,以及脚趾完全伸直到完全蜷缩的缓慢重复动作;②膝上截肢及膝离断者,行上述动作加上完全伸膝到完全屈膝的缓慢重复动作;③肘下截肢者,行手腕背伸最大角度到掌屈最大角度,以及手指完全伸直分开到完全握拳的缓慢重复动作;④肘上截肢及肘离断者,行上述动作加上完全伸肘到完全屈肘的缓慢重复动作;⑤双侧截肢者,由康复治疗师寻找与患者体型相近的志愿者,使用手机录下相应截肢部位对应的动作视频,调整视频方向与患者视觉体位一致,经由一台19英寸的电脑显示屏播放。
1.4 观察指标
治疗前收集患者基本信息,包括年龄、性别、截肢部位、截肢原因、病程等。在治疗前(t0)、治疗结束后即刻(t1)、治疗结束后3个月(t2),由对分组不知情、也不参与治疗的康复治疗师进行疼痛评定。疼痛评定包括VAS[17]和神经病理性疼痛四问(Douleur Neuropathique 4 questions, DN-4)[18]。VAS范围0(无痛)~10分(难以忍受的最剧烈的疼痛)。DN-4满分为10分,得分≥4分表明具有神经病理性疼痛。
1.5 统计学方法
分类变量使用频率、百分率表示,采用Pearson卡方检验分析。连续变量使用
$ \bar x \pm s $ (正态分布)或中位数(P25~P75)(非正态分布)描述统计,采用Student’s t检验(正态分布)或Mann-Whitney U检验(非正态分布)分析。通过重复测量方差分析后,组内前后比较采用配对t检验,组间比较采用独立样本t检验。P<0.05为差异有统计学意义。2. 结果
2.1 基线资料
完成治疗的26例受试者年龄为18~59岁,平均(39.73±12.64)岁,其中男性15例,女性11例,初次评估距离截肢手术时间平均(30.15±23.20) d。受试者截肢部位包括单侧上肢截肢8例,单侧下肢截肢16例,双上肢截肢1例,双下肢截肢1例,其中车祸伤15例,电击伤及机械碾压伤各4例,重物砸伤2例,刀刺伤1例。两组在男女比例、截肢时间、截肢部位、截肢原因、疼痛强度等方面差异均无统计学意义(P>0.05),受试者基本信息详见表1。
表 1 rTMS组和MT组的基线人口特征对比Table 1. Comparison of baseline demographic data between the rTMS group and the MT groupBasic information Total
(n=26)rTMS group (n=12) MT group (n=14) P Time since amputation/d 30.15±23.20 35.25±31.14 25.79±13.05 0.309 Age/yr. 39.73±12.64 44.00±12.74 36.07±11.79 0.112 Gender/case (%) 0.126 Male 15 (57.69) 5 (41.67) 10 (71.43) Female 11 (42.31) 7 (58.33) 4 (28.57) Levels of amputation/case (%) 0.364 Unilateral trans-humeral 3 (11.54) 1 (8.33) 2 (14.29) Unilateral trans-radial 5 (19.23) 2 (16.67) 3 (21.43) Unilateral trans-femoral 8 (30.77) 6 (50.00) 2 (14.29) Unilateral trans-tibial 5 (19.23) 1 (8.33) 4 (28.57) Unilateralknee disarticulation 3 (11.54) 1 (8.33) 2 (14.29) Bilateral trans-humeral 1 (3.85) 0 1 (7.14) Bilateral trans-femoral 1 (3.85) 1 (8.33) 0 Cause of injury/case (%) 0.501 Car accident 14 (53.85) 8 (66.67) 6 (42.86) Electrical shock injury 4 (15.38) 2 (16.67) 2 (14.29) Being caught in rolling machinery 5 (19.23) 2 (16.67) 3 (21.43) Crushing by heavy objects 2 (7.69) 0 2 (14.29) Knife stab 1 (3.85) 0 1 (7.14) VAS 6.23±0.99 6.08±1.08 6.29±0.91 0.610 DN-4 5.88±1.63 6.25±1.66 5.64±1.60 0.352 Data were shown as $ \bar x \pm s $ or case (%). rTMS: Repetitive transcranial magnetic stimulation; MT: Mirror therapy. 见表2和图1。纳入的截肢患者对PLP特征的描述共12种异样感觉,总体发生率最高的依次是麻刺感、刀割感、麻木感、放电感和灼烧感;在每一种异样感觉的报告上,rTMS组和MT组差异均无统计学意义(P>0.05)。
表 2 rTMS组和MT组PLP特征描述对比Table 2. Comparison of the features of PLP between the rTMS group and the MT groupPain characteristic Total/
case (%),
n=26rTMS group/
case (%),
n=12MT group/
case (%),
n=14P Burning 14 (53.85) 7 (58.33) 7 (50.00) 0.671 Freezing 5 (19.23) 4 (33.33) 1 (7.14) 0.091 Electric shocks 18 (69.23) 10 (83.33) 8 (57.14) 0.149 Tingling 23 (88.46) 10 (83.33) 13 (92.86) 0.449 Stabbing 22 (84.62) 10 (83.33) 12 (85.71) 0.867 Numbing 20 (76.92) 9 (75.00) 11 (78.57) 0.829 Itching 8 (30.77) 3 (25.00) 5 (35.71) 0.555 Brush allodynia 11 (42.31) 7 (58.33) 4 (28.57) 0.126 Unnatural position 10 (38.46) 4 (33.33) 6 (42.86) 0.619 Telescoping 4 (15.38) 1 (8.33) 3 (21.43) 0.356 Throbbing 6 (23.08) 1 (8.33) 5 (35.71) 0.099 Cramping 2 (7.69) 0 2 (14.29) 0.173 2.2 治疗前后疼痛对比
2.2.1 组间治疗前后疼痛对比
见表3。结果显示两组间在3个时间点的VAS及DN-4差异均无统计学意义(P>0.05)。
表 3 rTMS组和MT组的组间治疗前及治疗后疼痛评定对比Table 3. Comparison of pre-intervention and post-intervention pain measurements between the rTMS group and the MT groupVariable rTMS group (n=12) MT group (n=14) P VAS t0 6.08±1.08 6.29±0.91 0.610 t1 4 (1-5)* 4 (2-5)* 0.860 t2 2.58±2.39* 2.36±1.74*, Δ 0.783 DN-4 t0 6.25±1.66 5.64±1.60 0.352 t1 3.67±2.10# 3.64±1.65# 0.974 t2 3.33±2.27# 2.21±1.63#, ▲ 0.157 Data were shown as $ \bar x \pm s $ or median (P25-P75). rTMS: Repetitive transcranial magnetic stimulation; MT: Mirror therapy; t0: Assessment before treatment; t1: Assessment at the end of the treatment; t2: Assessment 3 months after treatment. *P<0.01, vs. VASt0 in the same group; #P<0.01, vs. DN-4t0 in the same group; ΔP<0.01, vs. VASt1 in the same group; ▲P<0.05, vs. DN-4t1 in the same group. 2.2.2 组内治疗前后疼痛对比
2.2.2.1 rTMS组
见表3。与t0相比,t1及t2的VAS和DN-4结果均降低(P<0.01);与t1相比,t2随访时的VAS和DN-4结果差异无统计学意义(P>0.05)。
2.2.2.2 MT组
见表3。与t0相比,t1及t2的VAS和DN-4结果差异有统计学意义(P<0.01);与t1相比,t2随访时的VAS和DN-4结果差异有统计学意义(P<0.05)。
2.3 两组间治疗前后疼痛差值对比
见表4。两组VAS及DN-4治疗前后差值(Δt0-t1),治疗后3个月与治疗前差值(Δt0-t2),治疗后3个月与治疗后差值(Δt1-t2),差异均无统计学意义(P>0.05)。
表 4 rTMS组和MT组治疗前后疼痛差值(Δ)对比Table 4. Comparison of changes in pain measurements between the rTMS group and MT group before and after the intervention (Δ)Outcome rTMS group (n=12) MT group (n=14) P VAS Δt0-t1 2 (0-4) 3 (2-3) 0.595 Δt0-t2 3.50±2.39 3.93±1.73 0.602 Δt1-t2 1.08±1.83 1.28±1.33 0.747 DN-4 Δt0-t1 2.58±2.15 2.00±1.75 0.454 Δt0-t2 2.92±2.68 3.43±1.65 0.557 Δt1-t2 0 (0-1) 1 (0-2) 0.095 Data were shown as $ \bar x \pm s $ or median (P25-P75). rTMS: Repetitive transcranial magnetic stimulation; MT: Mirror therapy; t0: Assessment before treatment; t1: Assessment at the end of the treatment; t2: Assessment 3 months after treatment. 2.4 安全性与副作用
26例完成试验的患者在研究过程中未见头晕、头痛等异常。
3. 讨论
本研究结果显示,rTMS组和MT组的治疗前后PLP评估结果差异均有统计学意义,证明MT和rTMS对截肢后PLP有改善作用,且可维持至治疗结束后的第3个月;rTMS组和MT组在各时点的PLP评估结果组间差异均无统计学意义,表明rTMS并不比MT对截肢后PLP更有效。
MT和rTMS治疗截肢后PLP的潜在机制存在差别。有学者先后在猴和人身上发现截肢后的运动皮质重组现象[19-20],并发现这种现象与PLP的程度相关[21]。MT可能通过为患者提供幻肢运动的视觉刺激和运动想象[22],阻碍皮质重组。利用镜像神经元系统激活大脑可塑性,通过视觉反馈、运动观察、运动想象、运动模仿抑制大脑中枢功能区异常移位[22],并向患者提供以视觉为主导的多感觉协同的错觉,从而增强患者对幻肢感的控制,减轻不适的幻肢感和PLP。rTMS则可能通过调节与疼痛通路相关的各种神经递质[23],以及对深层和远端大脑结构的兴奋性调节[14]等方式,影响皮质重组[24]。rTMS刺激运动皮质区域减轻慢性疼痛,其潜在机制可能是调节了抑制性和兴奋性氨基酸(γ-氨基丁酸和谷氨酸)之间的失衡,从而调节了疼痛通路[23]。另外一种可能是,经过rTMS刺激后的运动皮质区的兴奋性改变,进一步引起皮质脊髓神经元兴奋性以及丘脑的活动的改变,从而影响眶上额叶皮质区、前扣带回及中脑导水管周围灰质等与疼痛、情绪相关的脑区[14]。不少神经生理学研究也在利用rTMS联合神经影像学手段来探索截肢后大脑神经可塑性及皮质重组过程。
由于rTMS治疗PLP的机制未得到统一的解释,目前关于rTMS治疗截肢后PLP的临床随机对照研究和个案报道,所使用的rTMS的频率、靶点、脉冲数、周期等参数也各不相同。GATZINSKY等[25]的系统评价发现靶点位于M1区的rTMS可以有效缓解慢性疼痛,但是效果短暂,需要定期连续多次使用rTMS才能获得更大更持久的效果。GEOFFREY等[26]的个案报道中,使用低频rTMS(1 Hz,2000个脉冲)作用于截肢部位对应的感觉皮质区,发现在第4次治疗结束后该患者VAS评分由5分降到2分;后来又添加高频rTMS(10 Hz,3000个脉冲)作用于左侧背外侧前额叶(DLPFC),行28次治疗后,该患者VAS评分由2分降到1分。DI ROLLO等[27]的个案研究也采用的低频rTMS(1 Hz,600个脉冲),作用部位为截肢部位同侧的M1区,经过3周的治疗,PLP VAS评分由6分降到4分。MALAVERA等[15]和AHMED等[16]的随机对照研究分别使用10 Hz(54例,1200个脉冲)和20 Hz(27例,2000个脉冲)的高频rTMS作用于截肢部位对应的M1区,都发现PLP明显改善(相较于假刺激),且在随访(15 d、1个月、2个月)中疗效依然存在。本研究采用1 Hz的低频rTMS,作用于截肢部位对应的M1区,900个脉冲,与上述研究使用的rTMS的频率和靶点各不相同。虽然目前的研究使用的参数各异,但其结果都显示rTMS对PLP的正向作用。
值得重视的是,PLP治疗过程中发生的不良反应,这影响临床治疗决策的选择。本研究中,4例退出者中,1例受试者在第1次行MT时,治疗3 min左右,诉明显“入镜”,感觉缺如肢体重现,且动作生动,然后发生剧烈的头晕、头痛、恶心,不能耐受治疗,休息5 min后再次尝试MT,依旧发生上诉反应,遂退出研究;1例受试者在第1次行rTMS治疗时,刺激2 min后,诉头晕、头痛,并要求退出治疗。MT的潜在不良反应在临床实践中常被康复治疗师提及,一些研究[28-30]也有报道,如PLP和幻肢感的加重、幻肢伸缩变形、恶心、想吐、头晕和悲伤情绪的发作等。治疗师在临床实践中应该在开始治疗前充分告知患者可能发生的不良反应,在反应强烈时停止治疗,并且确保患者仅在无痛活动范围内自愿移动幻肢。非侵入性和安全性往往是决策者选择rTMS作为治疗手段的重要原因,但是在治疗PLP时,对不良反应的监测应该被重视,并且做好应急预案。
本研究存在一定的局限性。首先,由于截肢患者数量有限,且只纳入药物治疗效果不佳的患者,本研究纳入的样本较少。其次,本研究建立在MT有效的基础上验证rTMS的疗效,未设置安慰剂对照组,无法完全排除PLP自发性缓解的可能。再次,在研究过程中,未对药物、假肢等干扰因素进行控制,可能影响PLP的进程。最后,本研究随访时间较短,仅为3个月。
综上所述,本研究结果显示,rTMS对截肢后PLP的改善具有正向作用,但并不比MT更有效,治疗师应该结合临床实际情况选择治疗方案,并且密切观察是否发生不良反应。PLP发生与缓解的神经生物学机制还需进一步的研究和探索,未来还需大样本、多中心、高质量的随机对照试验验证rTMS治疗截肢后PLP的疗效和安全性,以及个体化的治疗方案。
* * *
利益冲突 所有作者均声明不存在利益冲突
-
表 1 rTMS组和MT组的基线人口特征对比
Table 1 Comparison of baseline demographic data between the rTMS group and the MT group
Basic information Total
(n=26)rTMS group (n=12) MT group (n=14) P Time since amputation/d 30.15±23.20 35.25±31.14 25.79±13.05 0.309 Age/yr. 39.73±12.64 44.00±12.74 36.07±11.79 0.112 Gender/case (%) 0.126 Male 15 (57.69) 5 (41.67) 10 (71.43) Female 11 (42.31) 7 (58.33) 4 (28.57) Levels of amputation/case (%) 0.364 Unilateral trans-humeral 3 (11.54) 1 (8.33) 2 (14.29) Unilateral trans-radial 5 (19.23) 2 (16.67) 3 (21.43) Unilateral trans-femoral 8 (30.77) 6 (50.00) 2 (14.29) Unilateral trans-tibial 5 (19.23) 1 (8.33) 4 (28.57) Unilateralknee disarticulation 3 (11.54) 1 (8.33) 2 (14.29) Bilateral trans-humeral 1 (3.85) 0 1 (7.14) Bilateral trans-femoral 1 (3.85) 1 (8.33) 0 Cause of injury/case (%) 0.501 Car accident 14 (53.85) 8 (66.67) 6 (42.86) Electrical shock injury 4 (15.38) 2 (16.67) 2 (14.29) Being caught in rolling machinery 5 (19.23) 2 (16.67) 3 (21.43) Crushing by heavy objects 2 (7.69) 0 2 (14.29) Knife stab 1 (3.85) 0 1 (7.14) VAS 6.23±0.99 6.08±1.08 6.29±0.91 0.610 DN-4 5.88±1.63 6.25±1.66 5.64±1.60 0.352 Data were shown as $ \bar x \pm s $ or case (%). rTMS: Repetitive transcranial magnetic stimulation; MT: Mirror therapy. 表 2 rTMS组和MT组PLP特征描述对比
Table 2 Comparison of the features of PLP between the rTMS group and the MT group
Pain characteristic Total/
case (%),
n=26rTMS group/
case (%),
n=12MT group/
case (%),
n=14P Burning 14 (53.85) 7 (58.33) 7 (50.00) 0.671 Freezing 5 (19.23) 4 (33.33) 1 (7.14) 0.091 Electric shocks 18 (69.23) 10 (83.33) 8 (57.14) 0.149 Tingling 23 (88.46) 10 (83.33) 13 (92.86) 0.449 Stabbing 22 (84.62) 10 (83.33) 12 (85.71) 0.867 Numbing 20 (76.92) 9 (75.00) 11 (78.57) 0.829 Itching 8 (30.77) 3 (25.00) 5 (35.71) 0.555 Brush allodynia 11 (42.31) 7 (58.33) 4 (28.57) 0.126 Unnatural position 10 (38.46) 4 (33.33) 6 (42.86) 0.619 Telescoping 4 (15.38) 1 (8.33) 3 (21.43) 0.356 Throbbing 6 (23.08) 1 (8.33) 5 (35.71) 0.099 Cramping 2 (7.69) 0 2 (14.29) 0.173 表 3 rTMS组和MT组的组间治疗前及治疗后疼痛评定对比
Table 3 Comparison of pre-intervention and post-intervention pain measurements between the rTMS group and the MT group
Variable rTMS group (n=12) MT group (n=14) P VAS t0 6.08±1.08 6.29±0.91 0.610 t1 4 (1-5)* 4 (2-5)* 0.860 t2 2.58±2.39* 2.36±1.74*, Δ 0.783 DN-4 t0 6.25±1.66 5.64±1.60 0.352 t1 3.67±2.10# 3.64±1.65# 0.974 t2 3.33±2.27# 2.21±1.63#, ▲ 0.157 Data were shown as $ \bar x \pm s $ or median (P25-P75). rTMS: Repetitive transcranial magnetic stimulation; MT: Mirror therapy; t0: Assessment before treatment; t1: Assessment at the end of the treatment; t2: Assessment 3 months after treatment. *P<0.01, vs. VASt0 in the same group; #P<0.01, vs. DN-4t0 in the same group; ΔP<0.01, vs. VASt1 in the same group; ▲P<0.05, vs. DN-4t1 in the same group. 表 4 rTMS组和MT组治疗前后疼痛差值(Δ)对比
Table 4 Comparison of changes in pain measurements between the rTMS group and MT group before and after the intervention (Δ)
Outcome rTMS group (n=12) MT group (n=14) P VAS Δt0-t1 2 (0-4) 3 (2-3) 0.595 Δt0-t2 3.50±2.39 3.93±1.73 0.602 Δt1-t2 1.08±1.83 1.28±1.33 0.747 DN-4 Δt0-t1 2.58±2.15 2.00±1.75 0.454 Δt0-t2 2.92±2.68 3.43±1.65 0.557 Δt1-t2 0 (0-1) 1 (0-2) 0.095 Data were shown as $ \bar x \pm s $ or median (P25-P75). rTMS: Repetitive transcranial magnetic stimulation; MT: Mirror therapy; t0: Assessment before treatment; t1: Assessment at the end of the treatment; t2: Assessment 3 months after treatment. -
[1] ORTIZ-CATALAN M, GUDMUNDSDOTTIR R A, KRISTOFFERSEN M B, et al. Phantom motor execution facilitated by machine learning and augmented reality as treatment for phantom limb pain: A single group, clinical trial in patients with chronic intractable phantom limb pain. Lancet,2016,388(10062): 2885–2894. DOI: 10.1016/S0140-6736(16)31598-7
[2] YILDIRIM M, KANAN N. The effect of mirror therapy on the management of phantom limb pain. Agri,2016,28(3): 127–134. DOI: 10.5505/agri.2016.48343
[3] WEEKS S R, ANDERSON-BARNES V C, TSAO J W. Phantom limb pain: Theories and therapies. Neurologist,2010,16(5): 277–286. DOI: 10.1097/NRL.0b013e3181edf128
[4] KERN U, BUSCH V, ROCKLAND M, et al. PrevSalence and risk factors of phantom limb pain and phantom limb sensations in Germany. A nationwide field survey. Schmerz,2009,23(5): 479–488. DOI: 10.1007/s00482-009-0786-5
[5] BALAKHANLOU E, WEBSTER J, BORGIA M, et al. Frequency and severity of phantom limb pain in veterans with major upper limb amputation: Results of a national survey. PM R,2021,13(8): 827–835. DOI: 10.1002/pmrj.12485
[6] EPHRAIM P L, WEGENER S T, MACKENZIE E J, et al. Phantom pain, residual limb pain, and back pain in amputees: Results of a national survey. Arch Phys Med Rehabil,2005,86(10): 1910–1919. DOI: 10.1016/j.apmr.2005.03.031
[7] EICHENBERGER U, NEFF F, SVETICIC G, et al. Chronic phantom limb pain: The effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesth Analg,2008,106(4): 1265–1273. DOI: 10.1213/ane.0b013e3181685014
[8] AHMED A, BHATNAGAR S, MISHRA S, et al. Prevalence of phantom limb pain, stump pain, and phantom limb sensation among the amputated cancer patients in India: A prospective, observational study. Indian J Palliat Care,2017,23(1): 24–35. DOI: 10.4103/0973-1075.197944
[9] ICHINOSE A, SANO Y, OSUMI M, et al. Somatosensory feedback to the cheek during virtual visual feedback therapy enhances pain alleviation for phantom arms. Neurorehabil Neural Repair,2017,31(8): 717–725. DOI: 10.1177/1545968317718268
[10] BARBIN J, SEETHA V, CASILLAS J M, et al. The effects of mirror therapy on pain and motor control of phantom limb in amputees: A systematic review. Ann Phys Rehabil Med,2016,59(4): 270–275. DOI: 10.1016/j.rehab.2016.04.001
[11] KIKKERT S, MEZUE M, O'SHEA J, et al. Neural basis of induced phantom limb pain relief. Ann Neurol,2019,85(1): 59–73. DOI: 10.1002/ana.25371
[12] 王凤怡, 张嘉祺, 张梦杰, 等. 镜像疗法改善截肢患者幻肢感及幻肢痛疗效的系统评价. 中国循证医学杂志,2016,16(2): 160–165. [13] 张仁刚, 刘沙鑫, 王凤怡, 等. 重复性经颅磁刺激联合感知提醒对脑卒中患者单侧忽略的影响研究. 四川大学学报(医学版),2017,48(2): 309–313. [14] LEE J H, BYUN J H, CHOE Y R, et al. Successful treatment of phantom limb pain by 1 Hz repetitive transcranial magnetic stimulation over affected supplementary motor complex: A case report. Ann Rehabil Med,2015,39(4): 630–633. DOI: 10.5535/arm.2015.39.4.630
[15] MALAVERA A, SILVA F A, FREGNI F, et al. Repetitive transcranial magnetic stimulation for phantom limb pain in landmine victims: A double-blinded, randomized, sham-controlled trial. J Pain,2016,17(8): 911–918. DOI: 10.1016/j.jpain.2016.05.003
[16] AHMED M, MOHAMEDA S A S D. Long-term antalgic effects of repetitive transcranial magnetic stimulation of motor cortex and serum beta-endorphin in patients with phantom pain. Neurol Res, 2013,2011,33(9): 953–958. DOI: 10.1179/1743132811Y.0000000045
[17] 万丽, 赵晴, 陈军, 等. 疼痛评估量表应用的中国专家共识(2020版). 中华疼痛学杂志,2020,16(3): 177–187. DOI: 10.3760/cma.j.cn101379-20190915-00075 [18] 李君, 冯艺, 韩济生, 等. 三个中文版神经病理性疼痛诊断量表的制定与多中心验证. 中国疼痛医学杂志,2011,17(9): 549–553. DOI: 10.3969/j.issn.1006-9852.2011.09.011 [19] FLORENCE S L, KAAS J H. Large-scale reorganization at multiple levels of the somatosensory pathway follows therapeutic amputation of the hand in monkeys. J Neurosci,1995,15(12): 8083–8095. DOI: 10.1523/JNEUROSCI.15-12-08083.1995
[20] FLOR H, NIKOLAJSEN L, STAEHELIN JENSEN T. Phantom limb pain: A case of maladaptive CNS plasticity? Nat Rev Neurosci,2006,7(11): 873–881. DOI: 10.1038/nrn1991
[21] PACHECO-BARRIOS K, PINTO C B, SALEH VELEZ F G, et al. Structural and functional motor cortex asymmetry in unilateral lower limb amputation with phantom limb pain. Clin Neurophysiol,2020,131(10): 2375–2382. DOI: 10.1016/j.clinph.2020.06.024
[22] DIERS M, KAMPING S, KIRSCH P, et al. Illusion-related brain activations: A new virtual reality mirror box system for use during functional magnetic resonance imaging. Brain Res,2015,1594: 173–182. DOI: 10.1016/j.brainres.2014.11.001
[23] BLEAKMAN D, ALT A, NISENBAUM E S. Glutamate receptors and pain. Semin Cell Dev Biol,2006,17(5): 592–604. DOI: 10.1016/j.semcdb.2006.10.008
[24] NURMIKKO T, MACIVER K, BRESNAHAN R, et al. Motor cortex reorganization and repetitive transcranial magnetic stimulation for pain—A methodological study. Neuromodulation,2016,19(7): 669–678. DOI: 10.1111/ner.12444
[25] GATZINSKY K, BERGH C, LILJEGREN A, et al. Repetitive transcranial magnetic stimulation of the primary motor cortex in management of chronic neuropathic pain: A systematic review. Scand J Pain,2020,7;21(1): 8–21. DOI: 10.1515/sjpain-2020-0054
[26] GEOFFREY G, SONYA W, ASHLEYC, et al. Significant reduction in phantom limb pain after low-frequency repetitive transcranial magnetic stimulation to the primary sensory cortex. Mil Med,2015,180(1): 126–128. DOI: 10.7205/MILMED-D-14-00236
[27] DI ROLLO D, PALLANTI S, LAZZARO V. Phantom limb pain: Low frequency repetitive transcranial magnetic stimulation in unaffected hemisphere. Case Rep Med, 2011, 2011: 130751[2020-09-08]. https://doi.org/10.1155/2011/130751.
[28] CHAN B L, WITT R, CHARROW A P, et al. Mirror therapy for phantom limb pain. N Engl J Med,2007,357(21): 2206–2207. DOI: 10.1056/NEJMc071927
[29] FINN S B, PERRY B N, CLASING J E, et al. A randomized, controlled trial of mirror therapy for upper extremity phantom limb pain in male amputees. Front Neurol, 2017, 8: 267[2020-09-08]. https://doi.org/10.3389/fneur.2017.00267.
[30] ROTHGANGEL A, BRAUN S, WINKENS B, et al. Traditional and augmented reality mirror therapy for patients with chronic phantom limb pain (PACT study): Results of a three-group, multicentre single-blind randomized controlled trial. Clin Rehabil,2018,32(12): 1591–1608. DOI: 10.1177/0269215518785948
-
期刊类型引用(5)
1. 沈兴利,贺奇志,周黎明,赵林,汤壮,李星宇. 幻肢痛研究进展. 国际骨科学杂志. 2025(01): 18-22 . 百度学术
2. 詹宁,董继革,吴东宇,申岩. 非侵入性脑刺激治疗幻肢痛的研究进展. 中国康复医学杂志. 2024(10): 1554-1559 . 百度学术
3. 华莉,韩月,金思岐,赵悦,蔡峰,马烨. 感觉再教育训练结合镜像疗法对下肢截肢患者幻肢痛的治疗效果. 广西医学. 2024(09): 1361-1365 . 百度学术
4. 崔晨光,吕宇琪,韦子梦. 微信指导下居家镜像康复模式对截肢后幻肢痛患者的影响. 国际移植与血液净化杂志. 2024(06): 27-28 . 百度学术
5. 张云涵,吕文艳,刘家宝. 镜像疗法联合任务导向性训练对脑卒中偏瘫患者肢体功能恢复的影响. 四川大学学报(医学版). 2023(05): 1046-1051 . 百度学术
其他类型引用(1)