运动皮质刺激治疗神经病理性疼痛研究进展

不同原因导致的外周和中枢神经病理性疼痛在临床具有较高的发病率,且治疗效果往往欠佳。运动皮质刺激(motor cortex stimulation, MCS)是20世纪80年代出现的一种治疗慢性疼痛的方法,因其对疼痛良好的治疗效果而被越来越多的用于临床。近年来,更多的运动皮质刺激技术方法得以发展,镇痛效果也不断提高。本文主要梳理了在疼痛治疗中,硬膜外运动皮质刺激(epidural motor cortex stimulation, eMCS)、重复经颅磁刺激(transcranial magnetic repetitive stimulation, rTMS)、经颅直流电刺激(transcranial direct current stimulation, tDCS)的临床疗效和镇痛机制,以期推动运动皮质刺激镇痛的基础研究和临床应用。     

运动皮层电刺激术治疗顽固性疼痛的手术配合

运动皮层电刺激术(motor cortex sti mulation,MCS)是20世纪90年代国际上用于治疗顽固性疼痛的一种新方法。具有手术安全、疗效确切、可调控、可逆性等优点,为中枢性疼痛、幻肢痛、神经源性疼痛等顽固性疼痛的治疗提供了新的手段[1-2]。我科于2005年2~12月成功完成10例MCS手术,取得了满意的疗效。现将手术配合介绍如下。1临床资料本组10例,男9例,女1例。年龄28~69岁。主要症状为单侧或双侧肢体持续性疼痛,伴针刺感、烧灼感等异常不适。患者对此难以忍受,许多人甚至产生轻生的念头。其中单侧肢体疼痛5例,双侧肢体疼痛4例;中枢性疼痛8例,幻…     

周围神经电刺激治疗顽固性枕神经痛一例

2005年我院对一例慢性顽固性枕神经痛的患者实施了周围神经电刺激术，取得了很好的疗效，现报道如下。资料与方法1．一般资料患者男，63岁。诉右颈枕部疼痛30余年，有时放射到右头顶部，加重3年。疼痛呈针刺样或电击样，阵发性发着，持续时间由十分钟延长至约0．5～2小时／次，疼痛发作时VAS达8～9分。夜间发作明显，严重影响睡眠。曾在多家医院就诊，长期服用得理多及曲马多等药物、也行过针刀和射频等治疗，[第一段]     

周围神经电刺激对脑卒中患者运动皮质兴奋性的影响

目的:探讨周围神经电刺激(peripheral nerve stimulation,PNS)对脑卒中患者运动皮质兴奋性的影响。方法:将31例亚急性期脑卒中患者随机分为治疗组(15例)和对照组(16例)。两组患者在接受当日常规康复治疗之外,治疗组和对照组还分别接受2h的偏瘫侧上肢尺神经和桡神经的PNS治疗和伪PNS治疗。以患手第一骨间背侧肌为靶肌肉,在治疗前和治疗后应用经颅磁刺激(transcranial magnetic stimulation,TMS)检测卒中侧大脑静息运动阈值(resting motor threshold,r MT)、运动诱发电位募集曲线(recruitment curve,RC)、运动诱发电位峰值(peak motor evoked potential,p MEP)、皮质静息期(cortical silent period,CSP)等。结果:治疗前两组患者各相关指标均无显著性差异(P0.05)。治疗组患者接受PNS治疗后,RC斜率(P=0.01)及p MEP波幅(P=0.02)均显著增高,而r MT和CSP持续时间无显著变化(P0.05);对照组患者接受伪PNS治疗前后,各运动皮质兴奋性指标均无显著差异(P0.05)。重复测量方差分析显示RC斜率和p MEP波幅的时间×组别的交互效应显著(P=0.030和0.033),提示治疗前后RC斜率和p MEP波幅的变化两组之间差异具有显著性。结论:单次2h的偏瘫侧上肢周围神经电刺激可以增强亚急性期脑卒中患者患侧大脑运动皮质兴奋性。     

母语为汉语中国人语言区的皮质电刺激研究

目的 研究母语为汉语中国人语言区的构筑特点.方法 回顾性分析手术治疗20例优势半球语言区低级别胶质瘤.在唤醒麻醉下应用术中皮质电刺激确定语言区.结果 16例患者至少发现1个以上语言阳性部位,3例患者仅额叶有语言阳性部位,1例患者仅颞叶有语言阳性部位.语言阳性部位主要分布在侧裂周围,额下回语言阳性部位基本符合经典的Broca区;颞上回语言阳性部位明显多于颞中回.结论 个体之间语言阳性部位的分布存在较大变异,经典的语言-解剖模式需要改进.由于患者例数太少,目前的数据尚不能完全反映母语为汉语中国人语言区的构筑特点.     

神经电刺激治疗顽固性冠心病心绞痛

心绞痛 (ａｎｇｉｎａｐｅｃｔｏｒｉｓ)是心肌需氧与供氧失衡时 ,由于代谢异常产生的腺苷、乳酸、激肽等致痛物质造成的心脏痛觉。痛觉投射到与心脏相同的脊神经分布的皮肤区域 ,表现为胸痛 ,有时放射至左肩臂及手指内侧。此外还包括心肌缺血引起的其他不适 ,如极度疲乏、呼吸     

顽固性疼痛的治疗近况

顽固性疼痛是指一些或所有的治疗措施难以控制的持续疼痛。顽固性疼痛已经不是单纯的症状，而是一种疾病，使患者暂时或永久丧失工作能力，造成的不单是医学生物学问题，而且构成了社会学问题。世界卫生组织(WHO)制定了“三阶梯癌症疼痛治疗草案”，并提出“到2000年让癌痛患者不痛”的奋斗目标。WHO认为一个国家的吗啡消耗量是评价该国癌痛改善状况的一个重要指标。由于诸多因素，包括癌痛在内的顽固性疼痛并未得到很好的控制。近年来的调查显示仍有近62％的癌症患者遭受疼痛折磨。涉及顽固性疼痛的治疗方法越来越丰富，但药物治疗、神经阻滞、鞘内治疗以及电刺激镇痛是目前常用且易为患者接受的方法。这些治疗方法可产生持续的镇痛作用，具有一定的远期效果，在控制顽固性疼痛中具有重要的地位和作用。对近年来在这些治疗方法的进展作一简要回顾。     

枕骨大孔区畸形患者的电刺激运动诱发电位观察

对Ｘ线摄片证实的３２例枕骨大孔区畸形患者（其中３０例经手术治疗）进行了电刺激运动诱发电位（ＭＥＰ）测试，ＭＥＰ异常率为９３．８％，改变以中枢运动传导时间（ＣＭＣＴ）延迟为主．诱发电位改变与相应的临床体征及影像学所见相一致．提示ＭＥＰ可客观定量地反映本病患者运动功能的损害程度．９例患者术后１２～２１日进行了ＭＥＰ复查，术后复查ＭＥＰ可作为评价手术效果的客观指标．     

Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: Possible pathways for antinociception

Motor cortex stimulation is generally suggested as a therapy for patients with chronic and refractory neuropathic pain. However, the mechanisms underlying its analgesic effects are still unknown. In a previous study, we demonstrated that cortical stimulation increases the nociceptive threshold of naive conscious rats with opioid participation. In the present study, we investigated the neurocircuitry involved during the antinociception induced by transdural stimulation of motor cortex in naive rats considering that little is known about the relation between motor cortex and analgesia. The neuronal activation patterns were evaluated in the thalamic nuclei and midbrain periaqueductal gray. Neuronal inactivation in response to motor cortex stimulation was detected in thalamic sites both in terms of immunolabeling (Zif268/Fos) and in the neuronal firing rates in ventral posterolateral nuclei and centromedian-parafascicular thalamic complex. This effect was particularly visible for neurons responsive to nociceptive peripheral stimulation. Furthermore, motor cortex stimulation enhanced neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray. We have also observed a decreased Zif268, δ-aminobutyric acid (GABA), and glutamic acid decarboxylase expression within the same region, suggesting an inhibition of GABAergic interneurons of the midbrain periaqueductal gray, consequently activating neurons responsible for the descending pain inhibitory control system. Taken together, the present findings suggest that inhibition of thalamic sensory neurons and disinhibition of the neurons in periaqueductal gray are at least in part responsible for the motor cortex stimulation-induced antinociception.     

Brain opioid receptor density predicts motor cortex stimulation efficacy for chronic pain

The clinical effects of motor cortex stimulation (MCS) for neuropathic pain (NP) is thought to be mediated primarily by the secretion of endogenous opioids in humans and in animal models. Because opioid receptor density is itself decreased in patients with NP, we investigated whether the magnitude and distribution of the remaining opioid receptors in patients with NP could be biological predictors of the pain-relieving effects of MCS. Using ¹¹C-diprenorphine positron emission tomography scans, opioid receptor availability was assessed in 15 patients suffering refractory NP, who subsequently received chronically implanted MCS. All patients underwent 2 preoperative baseline scans at 2-wk intervals and were clinically assessed after 7 mo of chronic MCS. The levels of preoperative opioid-binding in the insula, thalamus, periaqueductal gray, anterior cingulate, and orbitofrontal cortex were significantly and positively correlated with postoperative pain relief at 7 mo. Patients with receptor density values below the lower limits in age-matched controls in the thalamus, periaqueductal gray and contralateral insula were the least likely to benefit from MCS. Opioid-receptor availability as shown in preoperative positron emission tomography scans appears to be related to the efficacy of MCS in NP and may help clinicians to select the candidates most likely to benefit from this procedure.     

Motor cortex stimulation for chronic neuropathic pain: a preliminary study of 10 cases

There is growing evidence to support the use of motor cortex stimulation (MCS) in the management of patients with chronic neuropathic pain. A prospective audit of ten patients using a modified staged technique for motor cortex implantation provides further evidence for the analgesic effectiveness of this technique. Ten patients suffering from phantom limb pain (n=3), post stroke pain (n=5), post traumatic neuralgia secondary to gunshot injury to the brain stem (n=1) and brachyalgia secondary to neuro-fibromatosis (n=150% pain relief) and long-term benefit in 4/5 of patients who initially responded to intermittent cortical stimulation (longest follow up 31 months after implantation). Of those patients who benefited two had post stroke pain, two phantom limb pain and one post-traumatic neuralgia. We conclude that motor cortex stimulation is an effective analgesic intervention in some patients with chronic neuropathic pain, but it is difficult if not impossible to predict those patients who may respond to treatment prior to implantation. Randomised controlled trials are now urgently needed to test the effectiveness of motor cortex stimulation under double-blind conditions.     

Transdural motor cortex stimulation reverses neuropathic pain in rats: A profile of neuronal activation

Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos‐IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos‐IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain.     

Short-term restoration of facial sensory loss by motor cortex stimulation in peripheral post-traumatic neuropathic pain

We report a case in which motor cortex stimulation (MCS) improved neuropathic facial pain due to peripheral nerve injury and restored tactile and thermal sensory loss. A 66-year-old man developed intractable trigeminal neuropathic pain after trauma of the supraorbital branch of the Vth nerve, associated with tactile and thermal sensory loss in the painful area. MCS was performed using neuronavigation and transdural electric stimulation to localize the upper facial area on the motor cortex. One month after surgery, pain was decreased from 80/100 to 20/100 on visual analogic scale, and sensory discrimination improved in the painful area. Two months after surgery, quantitative sensory testing confirmed the normalization of thermal detection thresholds. This case showed that MCS could restore tactile and thermal sensory loss, resulting from peripheral nerve injury. Although the mechanisms leading to this effect remain unclear, this observation enhanced the hypothesis that MCS acts through modulation of the sensory processing.     

Motor and parietal cortex stimulation for phantom limb pain and sensations

Limb amputation may lead to chronic painful sensations referred to the absent limb, ie phantom limb pain (PLP), which is likely subtended by maladaptive plasticity. The present study investigated whether transcranial direct current stimulation (tDCS), a noninvasive technique of brain stimulation that can modulate neuroplasticity, can reduce PLP. In 2 double-blind, sham-controlled experiments in subjects with unilateral lower or upper limb amputation, we measured the effects of a single session of tDCS (2 mA, 15 min) of the primary motor cortex (M1) and of the posterior parietal cortex (PPC) on PLP, stump pain, nonpainful phantom limb sensations and telescoping. Anodal tDCS of M1 induced a selective short-lasting decrease of PLP, whereas cathodal tDCS of PPC induced a selective short-lasting decrease of nonpainful phantom sensations; stump pain and telescoping were not affected by parietal or by motor tDCS. These findings demonstrate that painful and nonpainful phantom limb sensations are dissociable phenomena. PLP is associated primarily with cortical excitability shifts in the sensorimotor network; increasing excitability in this system by anodal tDCS has an antalgic effect on PLP. Conversely, nonpainful phantom sensations are associated to a hyperexcitation of PPC that can be normalized by cathodal tDCS. This evidence highlights the relationship between the level of excitability of different cortical areas, which underpins maladaptive plasticity following limb amputation and the phenomenology of phantom limb, and it opens up new opportunities for the use of tDCS in the treatment of PLP.     

Driving plasticity in the motor cortex in recurrent low back pain

The sensory and motor systems can reorganise following injury and learning of new motor skills. Recently we observed adaptive changes in motor cortical organisation in patients with recurrent low back pain (LBP), which are linked to altered motor coordination. Although changes in motor coordination can be trained and are associated with improved symptoms and function, it remains unclear whether these training‐induced changes are related to reorganisation of the motor cortex. This was investigated using the model of a delay in postural activation of the deep abdominal muscle, transversus abdominis (TrA) in 20 individuals with recurrent LBP. Subjects were allocated to either motor skill training that involved isolated voluntary contractions of TrA, or a control intervention of self‐paced walking exercise for 2 weeks. Electromyographic (EMG) activity was recorded from TrA bilaterally using intramuscular fine‐wire electrodes. Motor cortical organisation using transcranial magnetic stimulation (TMS) and postural activation associated with single rapid arm movements were investigated before and after training. Motor skill training induced an anterior and medial shift in motor cortical representation of TrA, towards that observed in healthy individuals from our previous study. This shift was associated with earlier postural activation of TrA. Changes were not observed following unskilled walking exercise. This is the first observation that motor training can reverse reorganisation of neuronal networks of the motor cortex in people with recurrent pain. The observed relationship between cortical reorganisation and changes in motor coordination following motor training provides unique insight into potential mechanisms that underlie recovery.     

Motor cortex stimulation reduces hyperalgesia in an animal model of central pain

Electrical stimulation of the primary motor cortex has been used since 1991 to treat chronic neuropathic pain. Since its inception, motor cortex stimulation (MCS) treatment has had varied clinical outcomes. Until this point, there has not been a systematic study of the stimulation parameters that most effectively treat chronic pain, or of the mechanisms by which MCS relieves pain. Here, using a rodent model of central pain, we perform a systematic study of stimulation parameters used for MCS and investigate the mechanisms by which MCS reduces hyperalgesia. Specifically, we study the role of the inhibitory nucleus zona incerta (ZI) in mediating the analgesic effects of MCS. In animals with mechanical and thermal hyperalgesia, we find that stimulation at 50 μA, 50 Hz, and 300 μs square pulses for 30 minutes is sufficient to reverse mechanical and thermal hyperalgesia. We also find that stimulation of the ZI mimics the effects of MCS and that reversible inactivation of ZI blocks the effects of MCS. These findings suggest that the reduction of hyperalgesia may be due to MCS effects on ZI.     

Sensorimotor integration in Complex Regional Pain Syndrome: a transcranial magnetic stimulation study

There is evidence that patients with Complex Regional Pain Syndrome (CRPS) have altered central sensorimotor processing. Sensory input can influence motor output either through indirect pathways or through direct connections from the sensory to motor cortex. The purpose of this study was to investigate sensorimotor interaction via direct connections in patients with CRPS and to compare the results with normal subjects'. Direct short-latency sensory-motor interaction was evaluated in eight patients with CRPS1 affecting a hand. Modulation of EMG responses to transcranial magnetic stimulation (TMS) induced by concomitant median nerve stimulation was measured, the so-called, short-latency afferent inhibition (SAI). Results were compared with eight normal subjects who were age and sex matched with the patients. As expected, all the normal subjects' EMG responses to TMS with median nerve stimulation were smaller than responses to TMS alone. In seven of the eight CRPS patients EMG responses to TMS were suppressed when paired with median nerve stimulation. Only one CRPS patient's results showed no suppression of EMG responses. These results suggest that the disease mechanisms of CRPS1 do not typically affect the direct neural circuit between sensory and motor cortex and that normal sensorimotor interaction is occurring via this route.