Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial

OBJECTIVE: To test the potential adjuvant effect of repetitive transcranial magnetic stimulation (rTMS) on motor learning in a group of stroke survivors undergoing constraint-induced therapy (CIT) for upper-limb hemiparesis. DESIGN: This was a prospective randomized, double-blind, sham-controlled, parallel group study. Nineteen individuals, one or more years poststroke, were randomized to either a rTMS + CIT (n = 9) or a sham rTMS + CIT (n = 10) group and participated in the 2-wk intervention. RESULTS: Regardless of group assignment, participants demonstrated significant gains on the primary outcome measures: the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL)--Amount of Use, and on secondary outcome measures including the Box and Block Test (BBT) and the MAL--How Well. Participants receiving rTMS failed to show differential improvement on either primary outcome measure. CONCLUSIONS: Although this study provided further evidence that even relatively brief sessions of CIT can have a substantial effect, it provided no support for adjuvant use of rTMS.     

Longstanding neuropathic pain after spinal cord injury is refractory to transcranial direct current stimulation: A randomized controlled trial

Neuropathic pain remains one of the most difficult consequences of spinal cord injury (SCI) to manage. It is a major cause of suffering and adds to the physical, emotional, and societal impact of the injury. Despite the use of the best available treatments, two thirds of people experiencing neuropathic pain after SCI do not achieve satisfactory pain relief. This study was undertaken in response to a recent clinical trial reporting short-term, clinically significant reductions in neuropathic SCI pain with primary motor cortex transcranial direct current stimulation (tDCS). In this investigation, we aimed to build on this previous clinical trial by extending the assessment period to determine the short-, medium-, and long-term efficacy of tDCS for the treatment of neuropathic pain after SCI. We found that, contrary to previous reports, after 5 tDCS treatment periods, mean pain intensity and unpleasantness rating were not significantly different from initial assessment. That is, in this trial tDCS did not provide any pain relief in subjects with neuropathic SCI pain (n = 10). A similar lack of effect was also seen after sham treatment. Because the injury duration in this study was significantly greater than that of previous investigations, it is possible that tDCS is an effective analgesic only in individuals with relatively recent injuries and pain. Future investigations comparing a range of injury durations are required if we are to determine whether this is indeed the case.     

Repetitive transcranial magnetic stimulation (rTMS) in experimentally induced and chronic neuropathic pain: a review.

Repetitive transcranial magnetic stimulation (rTMS) is an emerging technology that has been demonstrated to be useful in the treatment of depression and potentially useful in the management of several neurologic conditions. More recently, increasing attention has been directed at evaluating its efficacy in the treatment of patients with chronic neuropathic pain. We first discuss the literature examining the efficacy of rTMS in trials of experimentally induced acute pain as well as among patients with chronic pain. Examining frequency data obtained from the available literature, we attempted to identify some of the parameters of rTMS that appear to be related to its analgesic effects. An overview of the mechanisms underlying its potential analgesic role is discussed; generally, the influences of rTMS on cortical, and, indirectly, subcortical, neurons may reduce pain transmission ascending from spinothalamic tracts, thereby mitigating pain. Finally, we discuss some of the methodological issues and limitations of available studies and offer recommendations for further research. PERSPECTIVE: The authors provide a comprehensive review of rTMS use in the treatment of neuropathic pain in the literature available to date. Although the clinical usefulness of rTMS in pain has, as yet, to be determined, it offers insights into the pathophysiologic processes involved in the maintenance and exacerbation of chronic pain.     

Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: A randomized,multicenter, double-blind,crossover, sham-controlled trial

There is little evidence for multisession repetitive transcranial magnetic stimulation (rTMS) on pain relief in patients with neuropathic pain (NP), although single-session rTMS was suggested to provide transient pain relief in NP patients. We aimed to assess the efficacy and safety of 10 daily rTMS in NP patients. We conducted a randomized, double-blind, sham-controlled, crossover study at 7 centers. Seventy NP patients were randomly assigned to 2 groups. A series of 10 daily 5-Hz rTMS (500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patient with a follow-up of 17 days. The primary outcome was short-term pain relief assessed using a visual analogue scale (VAS). The secondary outcomes were short-term change in the short form of the McGill pain questionnaire (SF-MPQ), cumulative changes in the following scores (VAS, SF-MPQ, the Patient Global Impression of Change scale [PGIC], and the Beck Depression Inventory [BDI]), and the incidence of adverse events. Analysis was by intention to treat. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry. Sixty-four NP patients were included in the intention-to-treat analysis. The real rTMS, compared with the sham, showed significant short-term improvements in VAS and SF-MPQ scores without a carry-over effect. PGIC scores were significantly better in real rTMS compared with sham during the period with daily rTMS. There were no significant cumulative improvements in VAS, SF-MPQ, and BDI. No serious adverse events were observed. Our findings demonstrate that daily high-frequency rTMS of M1 is tolerable and transiently provides modest pain relief in NP patients.     

不同频率的高频重复经颅磁刺激对大鼠神经病理性疼痛的影响

目的观察高频重复经颅磁刺激(rTMS)对神经病理性疼痛模型大鼠的影响,并比较3种不同频率的rTMS对神经病理性疼痛的治疗效果,探索最佳治疗频率。方法选取健康成年雄性SD大鼠100只,随机分为假手术组、模型组、rTMS组、假刺激组,rTMS组又分为5 Hz组、10 Hz组、20 Hz组。于造模成功后第3天开始进行为期5 d或10 d的rTMS治疗。分别于术前、术后不同时间点对各组大鼠进行疼痛行为学评分,包括热痛敏缩足潜伏时(PWTL)、机械痛敏缩足阈值(PWMT)。结果治疗后各rTMS组的PWTL和PWMT值均较模型组不同程度增加,且10 Hz组、20 Hz组的PWTL、PWMT值增加较5 Hz组更明显,10 Hz和20 Hz组间的PWTL和PWMT值比较,差异无统计学意义(P>0.05)。结论不同频率rTMS治疗神经病理性疼痛的疗效不同,10 Hz和20 Hz的疗效优于5 Hz。     

重复经颅磁刺激联合帕利哌酮治疗青少年精神分裂症的随机对照研究

目的:探讨重复经颅磁刺激(repetitive transcranial magnetic stimulation, rTMS)联合帕利哌酮治疗青少年精神分裂症患者的疗效和安全性。方法:选择2014年3月至2017年5月于空军军医大学附属西京医院诊断为精神分裂症的青少年患者共80例,采用随机数字表法分为研究组与对照组,完成4周治疗及随访者为70例。研究组给予帕利哌酮及rTMS治疗,对照组给予帕利哌酮及伪刺激治疗,疗程均为4周。于治疗前(基线)、治疗2周、治疗4周给予阳性与阴性症状量表(positive and negative syndrome scale, PANSS)评定患者疗效,记录患者不良反应。结果:研究组治疗有效率为79.41%,对照组治疗有效率为55.56%,两组差异有统计学意义(P0.05);在治疗2周末、4周末时两组PANSS阴性症状评分及一般症状评分比较差异均无统计学意义,两组总分及阳性症状评分比较差异均有统计学意义(P0.05);两组不良反应比较差异无统计学意义。结论:rTMS可增强帕利哌酮对青少年精神分裂症患者的治疗效果,缩短起效时间,尤其在改善阳性症状中有更大作用,而不良反应无明显增加。     

重复经颅磁刺激对血管性痴呆大鼠认知功能影响的机制

目的研究重复经颅磁刺激对血管性痴呆（VD）大鼠认知功能康复的影响,探讨其康复治疗的分子学机制。 方法将36只Wistar大鼠随机分为正常对照组、VD模型组、VD低频组和VD高频组,VD低频组和VD高频组大鼠接受的刺激频率分别为0.5 Hz和5 Hz。采用Morris水迷宫测试方法检测各组大鼠认知功能,透射电镜下观察各组大鼠海马CA1区超微结构变化。应用实时定量逆转录多聚酶链反应（RT-PCR）、Western blot方法分别检测海马突触素、脑源性神经营养因子、N-甲基-D-天冬氨酸受体1的mRNA及蛋白表达。 结果大鼠Morris水迷宫测试结果提示2个治疗组认知功能有改善,各项指标均优于VD模型组（P<0.05）;透射电镜观察结果从形态学上显示2个治疗组突触界面曲率、突触后致密物质厚度、突触活性带长度均较VD模型组增加（P<0.05）。2个治疗组各检测因子表达量也明显高于VD模型组（P<0.05）。 结论重复经颅磁刺激对VD致认知功能障碍有治疗作用,其机制可能与其促进海马突触素、脑源性神经营养因子、N-甲基-D-天冬氨酸受体1的表达有关。     

Repetitive transcranial magnetic stimulation for post-traumatic stress disorder: Lights and shadows

We have read with interest the publication that describes the available data related to the use of neuromodulation strategies for the treatment of post-traumatic stress disorder (PTSD). Despite treatment advances, however, a substantial proportion of PTSD patients receiving psychological and/or pharmacological treatment do not reach an adequate clinical response. In their paper, the authors draw attention to the current understanding of the use of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for PTSD. Most of the previous studies indeed applied both inhibitory (1 Hz) and excitatory (> 1 Hz, up to 20 Hz) rTMS to the right and/or left dorsolateral prefrontal cortex. Despite larger therapeutic effects observed when high-frequency stimulation was applied, the question of which side and frequency of stimulation is the most successful is still debated. The authors also reported on the after-effect of rTMS related to neuroplasticity and identified the intermittent theta burst stimulation as a technique of particular interest because of it showed the most effective improvement on PTSD symptoms. However, although numerous studies have highlighted the possible beneficial use of rTMS protocols for PTSD, the exact mechanism of action remains unclear. In their conclusions, the authors stated that rTMS has been demonstrated to be effective for the treatment of PTSD symptoms. Nevertheless, we believe that further research with homogeneous samples, standardized protocols, and objective outcome measures is needed to identify specific therapeutic targets and to better define significant changes when active and sham stimulation procedures are compared.     

Repetitive transcranial magnetic stimulation of motor cortex after stroke: a focused review

Repetitive Transcranial Magnetic Stimulation (rTMS) is known to modulate cortical excitability and has thus been suggested to be a therapeutic approach for improving the efficacy of rehabilitation for motor recovery after stroke. In addition to producing effects on cortical excitability, stroke may affect the balance of transcallosal inhibitory pathways between motor primary areas in both hemispheres: the affected hemisphere (AH) may be disrupted not only by the infarct itself but also by the resulting asymmetric inhibition from the unaffected hemisphere, further reducing the excitability of the AH. Conceptually, therefore, rTMS could be used therapeutically to restore the balance of interhemispheric inhibition after stroke. rTMS has been used in two ways: low-frequency stimulation (≤1 Hz) to the motor cortex of the unaffected hemisphere to reduce the excitability of the contralesional hemisphere or high-frequency stimulation (>1 Hz) to the motor cortex of the AH to increase excitability of the ipsilesional hemisphere. The purpose of this systematic review is to collate evidence regarding the safety and efficacy of high-frequency rTMS to the motor cortex of the AH. The studies included investigated the concurrent effects of rTMS on the excitability of corticospinal pathways and upper-limb motor function in adults after stroke. This review suggests that rTMS applied to the AH is a safe technique and could be considered an effective approach for modulating brain function and contributing to motor recovery after stroke. Although the studies included in this review provide important information, double-blinded, sham-controlled Phase II and Phase III clinical trials with larger sample sizes are needed to validate this novel therapeutic approach.     

重复经颅磁刺激治疗脑卒中后下肢运动功能障碍的Scoping综述

目的 总结分析重复经颅磁刺激(rTMS)治疗脑卒中后下肢运动功能障碍的刺激方案。方法 检索建库至2022年8月17日Web of Science、PubMed、中国知网、万方数据库中rTMS治疗脑卒中后下肢运动功能障碍的相关文献。采用物理治疗证据数据库(PEDro)量表对纳入文献进行质量评价。由两名研究人员筛选文献、整理资料并进行Scoping综述。结果 最终纳入文献21篇,20项研究结果显示rTMS治疗有益于脑卒中后下肢运动功能障碍的恢复,1项研究结果为阴性。所有研究结果均提示rTMS治疗安全性良好,无严重不良反应。纳入研究中受试者情况、研究设计方案、刺激疗程、线圈类型及刺激部位、运动诱发电位的测定等均存在异质性。结论 rTMS治疗脑卒中后下肢运动功能障碍的研究需要结合脑卒中的病程和损伤的程度来制定刺激方案。同时,需要更多同类型设计及刺激方案信息完整的真刺激对照假刺激的rTMS研究来提高其应用的证据水平。     

Intramuscular neuromuscular electric stimulation for poststroke shoulder pain: a multicenter randomized clinical trial

OBJECTIVE: To assess the effectiveness of intramuscular neuromuscular electric stimulation (NMES) in reducing poststroke shoulder pain. DESIGN: Multicenter, single-blinded, randomized clinical trial. SETTING: Ambulatory centers of 7 academic rehabilitation centers in the United States. PARTICIPANTS: Volunteer sample of 61 chronic stroke survivors with shoulder pain and subluxation. INTERVENTION: Treatment subjects received intramuscular NMES to the supraspinatus, posterior deltoid, middle deltoid, and trapezius for 6 hours a day for 6 weeks. Control subjects were treated with a cuff-type sling for 6 weeks.Main outcome measure Brief Pain Inventory question 12 (BPI 12), an 11-point numeric rating scale administered in a blinded manner at the end of treatment, and at 3 and 6 months posttreatment. RESULTS: The NMES group exhibited significantly higher proportions of success based on the 3-point or more reduction in BPI 12 success criterion at the end of treatment (65.6% vs 24.1%, P<.01), at 3 months (59.4% vs 20.7%, P<.01), and at 6 months (59.4% vs 27.6%, P<.05). By using the most stringent "no pain" criterion, the NMES group also exhibited significantly higher proportions of success at the end of treatment (34.4% vs 3.4%, P<.01), at 3 months (34.4% vs 0.0%, P<.001), and at 6 months (34.4% vs 10.3%, P<.05). CONCLUSIONS: Intramuscular NMES reduces poststroke shoulder pain among those with shoulder subluxation and the effect is maintained for at least 6 months posttreatment.     

Effectiveness of repetitive trancranial or peripheral magnetic stimulation in neuropathic pain

Purpose: Maladaptive plasticity in the sensorimotor system, following neurological lesions or diseases, plays a central role in the generation and maintenance of neuropathic pain. Repetitive magnetic stimulation of the central and peripheral nervous system has gained relevance as noninvasive approach for neuromodulation and pain relief. Systematic reviews that evaluate the effectiveness and specificity of different protocols of repetitive magnetic stimulation to control neuropathic pain in clinical populations have the potential to improve the therapeutic applicability of this technique.

Methods: Studies whose primary goal was to evaluate the effectiveness of repetitive magnetic stimulation for the treatment of various types of neuropathic pain published in PubMed until August 2015 have been included in this systematic review.

Results: A total of 39 articles fulfilling the inclusion criteria were analyzed of which 37 studies investigated pain modulation using repetitive magnetic stimulation over the motor or non-motor cortices and two studies evaluated pain modulation using repetitive peripheral magnetic stimulation protocols.

Conclusions: Repetitive transcranial magnetic stimulation of the primary motor cortex using high frequency stimulation protocols can effectively reduce neuropathic pain, particularly in individuals with pain related to non-cerebral lesions. The application of multiple sessions can lead to long-lasting pain modulation and cumulative effects.

• Implications for Rehabilitation

• Maladaptive plasticity plays a central role in sensitization of nociceptive pathways, generation and maintainance of neuropathic pain;

• Most neuropathic pain conditions are refractory to pharmacological therapies;

• Repetitive magnetic stimulation of the central and peripheral nervous system has gained relevance as noninvasive approach for neuromodulation and pain relief.

     

The validity of the neuropathic pain scale for assessing diabetic neuropathic pain in a clinical trial

OBJECTIVES: In controlled trials of analgesics for the treatment of neuropathic pain, the primary outcome variable is most often a measure of global pain intensity. However, because neuropathic pain is associated with a variety of pain sensations, the effects of analgesic treatments on different sensations could go undetected if specific pain qualities are not assessed. This study sought to evaluate the utility of assessing the multiple components of neuropathic pain in an analgesic clinical trial. METHODS: One hundred fifty-nine subjects with diabetes-related foot pain were randomly assigned to receive an active analgesic (controlled-release oxycodone) or matching placebo for 6 weeks. A multidimensional measure of neuropathic pain, the Neuropathic Pain Scale (NPS), was administered before, during, and after study treatment. RESULTS: Relative to placebo, the opioid analgesic produced statistically significantly greater decreases in global pain intensity, pain unpleasantness, and sharp, dull, and deep pain sensations. Responder analyses indicated a higher rate of responding to the opioid condition, relative to placebo, for intense, unpleasant, deep, and surface pain. The opioid analgesic did not significantly reduce hot, cold, itchy, or sensitive pain sensations compared with placebo in either analysis. CONCLUSIONS: These findings support the utility of the NPS for characterizing the multidimensional nature of the neuropathic pain experience and for detecting changes in neuropathic pain with treatment.     

A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain.

The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use "medical marijuana," and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PERSPECTIVE: This study adds to a growing body of evidence that cannabis may be effective at ameliorating neuropathic pain, and may be an alternative for patients who do not respond to, or cannot tolerate, other drugs. However, the use of marijuana as medicine may be limited by its method of administration (smoking) and modest acute cognitive effects, particularly at higher doses.     

重复经颅磁刺激联合针刺治疗脊髓损伤后神经病理性疼痛的临床研究

目的：观察重复经颅磁刺激（rTMS）联合针刺治疗脊髓损伤（SCI）后神经病理性疼痛（NP）的临床疗效。方法：按随机数字表法将99例SCI后NP患者分成对照组、针刺组和联合组,各33例。对照组进行常规基础治疗,针刺组在对照组基础上进行针刺治疗,联合组在针刺组基础上进行rTMS治疗。分别于治疗前及治疗6周后对3组患者进行视觉模拟量表（VAS）、汉密顿抑郁量表（HAMD）、汉密顿焦虑量表(HAMA)及生活质量SF-36量表评估。结果：治疗6周后,3组患者VAS、HAMD和HAMA评分较治疗前均明显降低（P＜0.05）,SF-36量表各项评分较治疗前均明显升高（P＜0.05）;针刺组VAS、HAMD和HAMA评分较对照组均有降低（P＜0.05）,SF-36量表各项评分较对照组均有升高（P＜0.05）;联合组VAS、HAMD和HAMA评分较针刺组和对照组均有降低（P＜0.05）,SF-36量表各项评分较针刺组和对照组均有升高（P＜0.05）。结论：rTMS联合针刺治疗SCI后NP患者,有助于改善患者临床疼痛现象,且在改善患者情绪和生活质量方面疗效显著。