tDCS modulates cortical nociceptive processing but has little to no impact on pain perception

Transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. Several studies suggest clinical efficacy in chronic pain syndromes. However, little is known regarding its effects on cortical pain processing. In this double-blind, randomized, cross-over, sham controlled study, we examined the effects of anodal, cathodal, and sham stimulation of the left motor cortex in 16 healthy volunteers using functional imaging during an acute heat pain paradigm as well as pain thresholds, pain intensity ratings, and quantitative sensory testing. tDCS was applied at 1 mA for 15 minutes. Neither cathodal nor anodal tDCS significantly changed brain activation in response to nociceptive stimulation when compared with sham stimulation. However, contrasting the interaction of stimulation modes (anodal/cathodal) resulted in a significant decrease of activation in the hypothalamus, inferior parietal cortex, inferior parietal lobule, anterior insula, and precentral gyrus, contralateral to the stimulation site after anodal stimulation, which showed the opposite behavior after cathodal stimulation. Pain ratings and heat hyperalgesia showed only a subclinical pain reduction after anodal tDCS. Larger-scale clinical trials using higher tDCS intensities or longer durations are necessary to assess the neurophysiological effect and subsequently the therapeutic potential of tDCS.     

Anodal Transcranial Direct Current Stimulation Reduces Secondary Hyperalgesia Induced by low Frequency Electrical Stimulation in Healthy Volunteers

The aim of the study was to determine whether transcranial direct current stimulation (tDCS) reduced pain and signs of central sensitization induced by low frequency electrical stimulation in healthy volunteers. Thirty-nine participants received tDCS stimulation under 4 different conditions: anodal tDCS of the primary motor cortex (M1), anodal tDCS of the dorsolateral prefrontal cortex (DLPFC), anodal tDCS over M1 and DLPFC concurrently, and sham tDCS. Participants were blind to the tDCS condition. The order of the conditions was randomized among participants. Pain ratings to pinpricks, the current level that evoked moderate pain, and pain induced by low frequency electrical stimulation were assessed in the forearm by an experimenter who was blind to the tDCS conditions. Anodal tDCS at M1 increased the current level that evoked moderate pain compared to sham and other conditions. Anodal tDCS of DLPFC completely abolished secondary hyperalgesia. Unexpectedly, however, concurrent anodal tDCS over M1 and DLPFC did not reduce pain or hyperalgesia more than M1 alone or DLPFC alone. Overall, these findings suggest that anodal tDCS over M1 suppresses pain, and that anodal tDCS over DLPFC modulates secondary hyperalgesia (a sign of central sensitization) in healthy participants.PerspectiveAnodal transcranial current stimulation (atDCS) at the left motor cortex and the dorsolateral prefrontal cortex increased the electrically-evoked pain threshold and reduced secondary hyperalgesia in healthy participants. Replication of this study in chronic pain populations may open more avenues for chronic pain treatment.     

经颅直流电刺激同步吞咽任务对健康人吞咽皮质运动中枢的影响

目的探索经颅直流电刺激（tDCS）同步吞咽任务对吞咽运动中枢的神经电生理学影响。 方法采用自身对照,双盲设计。选取健康受试者20例,先后给予阳极tDCS(a-tDCS)、阴极tDCS(c-tDCS)和虚假tDCS（s-tDCS）三种刺激模式,以吞咽强投射区为靶半球进行干预,并同步完成用力吞咽任务。单脉冲经颅磁刺激分别刺激双侧吞咽皮质代表区,记录tDCS干预前以及干预后5、30、60和90min舌骨上肌群的运动诱发电位（MEP）;采用两因素重复测量的方差分析对数据进行统计学处理。 结果tDCS干预因素可影响双侧吞咽运动皮质的兴奋性［同侧,F(2,28)=241.2,P<0.01;对侧,F(1,20)=29.5,P<0.01］。时间因素和tDCS干预因素有交互作用［同侧,F(3,46)=25.4,P<0.01;对侧,F(4,53)=6.6,P<0.01］。其中s-tDCS对双侧兴奋性的影响差异无统计学意义［同侧,P=0.894;对侧,P=0.354］。与s-tDCS相比,a-tDCS提高了刺激同侧的兴奋性,而不是对侧［同侧,MEP均值差值为21%±2%,95%可信区间为15%～27%,P<0.01;对侧,MEP均值差值为1%±2%,95%可信区间为-3.4%～6.5%,P>0.05］。与s-tDCS相比,c-tDCS抑制同侧而增强对侧的皮质兴奋性［同侧,MEP均值差值为-21%±2%,95%可信区间为-18%～-42%,P<0.01;对侧,MEP均值差值为20%±3%,95%可信区间为12%～29%,P<0.01］。 结论tDCS同时结合吞咽任务对吞咽运动中枢的影响具有极性依赖性和刺激半球依赖性特征;a-tDCS可以提高同侧吞咽皮质运动区的兴奋性,而c-tDCS则在抑制同侧吞咽运动皮质同时兴奋对侧吞咽皮质区。     

Anodal Transcranial Direct Current Stimulation of the Motor Cortex Ameliorates Chronic Pain and Reduces Short Intracortical Inhibition

ContextConsecutive sessions of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) may be a suitable therapy to treat chronic pain, as it can modulate neural activities in the stimulated and interconnected regions.ObjectivesThe present study investigated the analgesic effect of five consecutive days of anodal/sham tDCS using subjective (visual analog scale [VAS]) and objective (cortical excitability measured by transcranial magnetic stimulation [TMS]) measurements.MethodsPatients with therapy-resistant chronic pain syndromes (trigeminal neuralgia, poststroke pain syndrome, back pain, fibromyalgia) participated. As this clinical trial was an exploratory study, statistical analyses implemented exploratory methods. Twelve patients, who underwent both anodal and sham tDCS, were analyzed using a crossover design. An additional nine patients had only anodal or sham stimulation. tDCS was applied over the hand area of the M1 for 20 minutes, at 1 mA for five consecutive days, using a randomized, double-blind design. Pain was assessed daily using a VAS rating for one month before, during, and one month post-stimulation. M1 excitability was determined using paired-pulse TMS.ResultsAnodal tDCS led to a greater improvement in VAS ratings than sham tDCS, evident even three to four weeks post-treatment. Decreased intracortical inhibition was demonstrated after anodal stimulation, indicating changes in cortico-cortical excitability. No patient experienced severe adverse effects; seven patients suffered from light headache after anodal and six after sham stimulation.ConclusionResults confirm that five daily sessions of tDCS over the hand area of the M1 can produce long-lasting pain relief in patients with chronic pain.     

Site-specific Effects of Transcranial Direct Current Stimulation on Sleep and Pain in Fibromyalgia: A Randomized, Sham-controlled Study

Objective: To investigate whether active anodal transcranial direct current stimulation (tDCS) (of dorsolateral prefrontal cortex [DLPFC] and primary motor cortex [M1]) as compared to sham treatment is associated with changes in sleep structure in fibromyalgia. Methods: Thirty‐two patients were randomized to receive sham stimulation or active tDCS with the anode centered over M1 or DLPFC (2 mA, 20 minutes for five consecutive days). A blinded evaluator rated the clinical symptoms of fibromyalgia. All‐night polysomnography was performed before and after five consecutive sessions of tDCS. Results: Anodal tDCS had an effect on sleep and pain that was specific to the site of stimulation: such as that M1 and DLPFC treatments induced opposite effects on sleep and pain, whereas sham stimulation induced no significant sleep or pain changes. Specifically, whereas M1 treatment increased sleep efficiency (by 11.8%, P = 0.004) and decreased arousals (by 35.0%, P = 0.001), DLPFC stimulation was associated with a decrease in sleep efficiency (by 7.5%, P = 0.02), an increase in rapid eye movement (REM) and sleep latency (by 47.7%, P = 0.0002, and 133.4%, P = 0.02, respectively). In addition, a decrease in REM latency and increase in sleep efficiency were associated with an improvement in fibromyalgia symptoms (as indexed by the Fibromyalgia Impact Questionnaire). Finally, patients with higher body mass index had the worse sleep outcome as indexed by sleep efficiency changes after M1 stimulation. Interpretation: Our findings suggest that one possible mechanism to explain the therapeutic effects of tDCS in fibromyalgia is via sleep modulation that is specific to modulation of primary M1 activity. ?     

Noninvasive cortical modulation of experimental pain

Noninvasive cortical stimulation (NICS) can produce analgesic effects by means of repetitive transcranial magnetic stimulation or transcranial direct current stimulation (tDCS). Such effects have been demonstrated on chronic ongoing pain, as in acute provoked pain. The investigation of induced changes in the perception of experimental pain by NICS could help clinicians and researchers to better understand the mechanisms of action involved with these techniques and the role played by the cortex in the integration of nociceptive information. This review presents current literature data on the modulation of experimental pain perception by cortical stimulation. The observations found that NICS analgesic effects depend on the method used to provoke pain (referring to the type of nerve fibers and neural circuits that are recruited to mediate pain) and the parameters of cortical stimulation (especially the nature of the cortical target). The motor cortex (precentral cortical area) is the most widely used target for pain modulation. However, other targets, such as the dorsolateral prefrontal cortex, could be of particular interest to modulate various components of pain. Further developments in NICS techniques, such as image-guided navigated brain stimulation, might lead to improvement in the beneficial effects of NICS on pain. Finally, we discuss whether the results obtained in experimental pain can be transposed to the problem of chronic pain and whether they can be used to optimize cortical stimulation therapy for pain disorders.     

A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury

Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.     

Transcranial direct current stimulation over somatosensory cortex decreases experimentally induced acute pain perception

OBJECTIVE: Multiple cortical areas including the primary somatosensory cortex are known to be involved in nociception. The aim of this study was to investigate the effect of transcranial direct current stimulation (tDCS) that modulates the cortical excitability painlessly and noninvasively, over somatosensory cortex on acute pain perception induced with a Tm:YAG laser. METHODS: Subjective pain rating scores and amplitude changes of the N1, N2, and P2 components of laser-evoked potentials of 10 healthy participants were analyzed before and after anodal, cathodal, and sham tDCS. RESULTS: Our results demonstrate that cathodal tDCS significantly diminished pain perception and the amplitude of the N2 component when the contralateral hand to the side of tDCS was laser-stimulated, whereas anodal and sham stimulation conditions had no significant effect. DISCUSSION: Our study highlights the antinociceptive effect of this technique and may contribute to the understanding of the mechanisms underlying pain relief. The pharmacologic prolongation of the excitability-diminishing after-effects would render the method applicable to different patient populations with chronic pain.     

Pergolide increases the efficacy of cathodal direct current stimulation to reduce the amplitude of laser-evoked potentials in humans

Transcranial direct current stimulation (tDCS) was recently reintroduced as a tool for inducing relatively long-lasting changes in cortical excitability in focal brain regions. Anodal stimulation over the primary motor cortex enhances cortical excitability, whereas cathodal stimulation decreases it. Prior studies have shown that enhancement of D2 receptor activity by pergolide consolidates tDCS-generated excitability diminution for up to 24 hours and that cathodal stimulation of the primary motor cortex diminishes experimentally induced pain sensation and reduces the N2-P2 amplitude of laser-evoked potentials immediately poststimulation. In the present study, we investigated the effect of pergolide and cathodal tDCS over the primary motor cortex on laser-evoked potentials and acute pain perception induced with a Tm:YAG laser in a double-blind, randomized, placebo-controlled, crossover study. The amplitude changes of laser-evoked potentials and subjective pain rating scores of 12 healthy subjects were analyzed prior to and following 15 minutes cathodal tDCS combined with pergolide or placebo intake at five different time points. Our results indicate that the amplitude of the N2 component was significantly reduced following cathodal tDCS for up to two hours. Additionally, pergolide prolonged the effect of the cathodal tDCS for up to 24 hours, and a significantly lowered pain sensation was observed for up to 40 minutes. Our study is a further step toward clinical application of cathodal tDCS over the primary motor cortex using pharmacological intervention to prolong the excitability-diminishing effect on pain perception for up to 24 hours poststimulation. Furthermore, it demonstrates the potential for repetitive daily stimulation therapy for pain patients.     

Transkranielle repetitive Magnet- und Gleichstromstimulation in der Schmerztherapie

Neuroplasticity is the ability of the central nervous system to induce functional and microstructural changes in order to adapt to a new environment. However, so-called maladaptive neuroplasticity can also bring disadvantages, such as reduced inhibition of input signals, one of the suspected causes of chronic pain. With the method of repetitive transcranial magnetic stimulation (rTMS) a technique has been developed that makes it possible to study cortical excitability changes in the human brain non-invasively over a long time. Electrophysiological studies have shown that the application of rTMS over the primary motor cortex induces a facilitatory or inhibitory effect on the corticospinal and cortico-cortical excitability depending on the protocol used. The results of the clinical studies published suggest that rTMS can inhibit pain perception with regard to chronic pain and in experimentally induced pain conditions. An alternative method to induce neuroplastic changes is transcranial direct current stimulation (tDCS). tDCS acts primarily on the membrane potential, by hyper- or depolarizing it. The induced after-effects are NMDA receptor dependent. The effectiveness of tDCS is currently being explored in migraine research as well as experimentally induced and chronic pain conditions. In phase II trials its efficacy has been demonstrated. Ongoing studies are focusing on management of the placebo effect; however, it is easier to control this effect in tDCS compared to rTMS. Phase III trials are currently in preparation.     

Effects of motor cortex modulation and descending inhibitory systems on pain thresholds in healthy subjects

Pain modulation can be achieved using neuromodulatory tools that influence various levels of the nervous system. Transcranial direct current stimulation (tDCS), for instance, has been shown to reduce chronic pain when applied to the primary motor cortex. In contrast to this central neuromodulatory technique, diffuse noxious inhibitory controls (DNIC) refers to endogenous analgesic mechanisms that decrease pain following the introduction of heterotopic noxious stimuli. We examined whether combining top-down motor cortex modulation using anodal tDCS with a bottom-up DNIC induction paradigm synergistically increases the threshold at which pain is perceived. The pain thresholds of 15 healthy subjects were assessed before and after administration of active tDCS, sham tDCS, cold-water-induced DNIC, and combined tDCS and DNIC. We found that both tDCS and the DNIC paradigm significantly increased pain thresholds and that these approaches appeared to have additive effects. Increase in pain threshold following active tDCS was positively correlated with baseline N-acetylaspartate in the cingulate cortex and negatively correlated with baseline glutamine levels in the thalamus as measured by magnetic resonance spectroscopy. These results suggest that motor cortex modulation may have a greater analgesic effect when combined with bottom-up neuromodulatory mechanisms, presenting new avenues for modulation of pain using noninvasive neuromodulatory approaches. PERSPECTIVE: This article demonstrates that both noninvasive motor cortex modulation and a descending noxious inhibitory controls paradigm significantly increase pain thresholds in healthy subjects and appear to have an additive effect when combined. These results suggest that existing pain therapies involving DNIC may be enhanced through combination with noninvasive brain stimulation.     

Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia

Background

Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing.

Methods

Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20 minutes over two weeks using anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0–10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS.

Results

Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported.

Conclusion

Anodal tDCS over two weeks ameliorates intensity of pain in TN. It may become a valuable treatment option for patients unresponsive to conventional treatment.     

经颅直流电刺激结合功能性电刺激对脑卒中平台期患者上肢运动功能康复影响的研究

目的:将经颅直流电刺激(tDCS)和功能性电刺激(FES)结合,观察这种联合治疗干预方式对脑卒中平台期患者上肢功能的影响。方法:3例脑卒中后平台期偏瘫患者在4周基线期后接受4周的tDCS结合FES治疗干预。干预前后用Fugl-Meyer上肢运动功能评分(U-FMA)、表面肌电图(sEMG)、经颅磁刺激(TMS)进行评定。结果:干预后U-FMA分数较干预前提高。7个主动肌中有5个表面肌电激活性干预前后有明显变化。用TMS成对刺激方法评估受试者健侧大脑短潜伏期皮质内抑制与短潜伏期皮质内易化结果显示部分的干预前后变化。结论:tDCS结合FES治疗干预改善了受试者上肢的运动功能,该方案可能是针对脑卒中平台期患者的一种有前景的干预康复方案。     

Alterations in pain processing circuitries in episodic migraine

BackgroundThe precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli.MethodsFunctional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity.ResultsDespite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons.ConclusionsThese data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.     

A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception

Several brain stimulation technologies are beginning to evidence promise as pain treatments. However, traditional versions of 1 specific technique, transcranial direct current stimulation (tDCS), stimulate broad regions of cortex with poor spatial precision. A new tDCS design, called high definition tDCS (HD-tDCS), allows for focal delivery of the charge to discrete regions of the cortex. We sought to preliminarily test the safety and tolerability of the HD-tDCS technique as well as to evaluate whether HD-tDCS over the motor cortex would decrease pain and sensory experience. Twenty-four healthy adult volunteers underwent quantitative sensory testing before and after 20 minutes of real (n = 13) or sham (n = 11) 2 mA HD-tDCS over the motor cortex. No adverse events occurred and no side effects were reported. Real HD-tDCS was associated with significantly decreased heat and cold sensory thresholds, decreased thermal wind-up pain, and a marginal analgesic effect for cold pain thresholds. No significant effects were observed for mechanical pain thresholds or heat pain thresholds. HD-tDCS appears well tolerated, and produced changes in underlying cortex that are associated with changes in pain perception. Future studies are warranted to investigate HD-tDCS in other applications, and to examine further its potential to affect pain perception. PERSPECTIVE: This article presents preliminary tolerability and efficacy data for a new focal brain stimulation technique called high definition transcranial direct current stimulation. This technique may have applications in the management of pain.     

Efficacy of Transcranial Direct Current Stimulation and Repetitive Transcranial Magnetic Stimulation for Treating Fibromyalgia Syndrome: A Systematic Review

Objective: To systematically review the literature to date applying repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) for patients with fibromyalgia syndrome (FMS). Method: Electronic bibliography databases screened included PubMed, Ovid MEDLINE, PsychINFO, CINAHL, and Cochrane Library. The keyword “fibromyalgia” was combined with (“transcranial” and “stimulation”) or “TMS” or “tDCS” or “transcranial magnetic stimulation” or “transcranial direct current stimulation”. Results: Nine of 23 studies were included; brain stimulation sites comprised either the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC). Five studies used rTMS (high‐frequency‐M1: 2, low‐frequency‐DLPFC: 2, high‐frequency‐DLPFC: 1), while 4 applied tDCS (anodal‐M1: 1, anodal‐M1/DLPFC: 3). Eight were double‐blinded, randomized controlled trials. Most (80%) rTMS studies that measured pain reported significant decreases, while all (100%) tDCS studies with pain measures reported significant decreases. Greater longevity of significant pain reductions was observed for excitatory M1 rTMS/tDCS. Conclusion: Studies involving excitatory rTMS/tDCS at M1 showed analogous pain reductions as well as considerably fewer side effects compared to FDA apaproved FMS pharmaceuticals. The most commonly reported side effects were mild, including transient headaches and scalp discomforts at the stimulation site. Yearly use of rTMS/tDCS regimens appears costly ($11,740 to 14,507/year); however, analyses to apapropriately weigh these costs against clinical and quality of life benefits for patients with FMS are lacking. Consequently, rTMS/tDCS should be considered when treating patients with FMS, particularly those who are unable to find adequate symptom relief with other therapies. Further work into optimal stimulation parameters and standardized outcome measures is needed to clarify associated efficacy and effectiveness.     

Transcranial direct current stimulation: electrode montage in stroke

Neurophysiological and computer modelling studies have shown that electrode montage is a critical parameter to determine the neuromodulatory effects of transcranial direct current stimulation (tDCS). We tested these results clinically by systematically investigating optimal tDCS electrode montage in stroke. Ten patients received in a counterbalanced and randomised order the following conditions of stimulation (i) anodal stimulation of affected M1 (primary motor cortex) and cathodal stimulation of unaffected M1 (‘bilateral tDCS’); (ii) anodal stimulation of affected M1 and cathodal stimulation of contralateral supraorbital area (‘anodal tDCS’); (iii) cathodal stimulation of unaffected M1 and anodal stimulation of contralateral supraorbital area (‘cathodal tDCS’); (iv) anodal stimulation of affected M1 and cathodal stimulation of contralateral deltoid muscle (‘extra-cephalic tDCS’) and (v) sham stimulation. We used the Jebsen–Taylor Test (JTT) as a widely accepted measure of upper limb function. Bilateral tDCS, anodal tDCS and cathodal tDCS were shown to be associated with significant improvements on the JTT. Placing the reference electrode in an extracephalic position and use of sham stimulation did not induce any significant effects. This small sham controlled cross-over clinical trial is important to provide additional data on the clinical effects of tDCS in stroke and for planning and designing future large tDCS trials in patients with stroke.     

Effects of Anodal Transcranial Direct Current Stimulation on Chronic Neuropathic Pain in Patients With Multiple Sclerosis

Neuropathic pain in patients with MS is frequent and is associated with a great interference with daily life activities. In the present study, we investigated whether anodal transcranial direct current stimulation (tDCS) may be effective in reducing central chronic pain in MS patients. Patients received sham tDCS or real tDCS in a 5-day period of treatment in a randomized, double blind, sham-controlled study. Pain was measured using visual analog scale (VAS) for pain and the short form McGill questionnaire (SF-MPQ). Quality of life was measured using the Multiple Sclerosis Quality of Life-54 scale (MSQoL-54). Depressive symptoms and anxiety were also evaluated as confounding factors using the Beck Depression Inventory (BDI) and VAS for anxiety. Evaluations were performed at baseline, immediately after the end of treatment, and once a week during a 3-week follow-up period. Following anodal but not sham tDCS over the motor cortex, there was a significant pain improvement as assessed by VAS for pain and McGill questionnaire, and of overall quality of life. No depression or anxiety changes were observed. Our results show that anodal tDCS is able to reduce pain-scale scores in MS patients with central chronic pain and that this effect outlasts the period of stimulation, leading to long-lasting clinical effects.PerspectiveThis article presents a new, noninvasive therapeutic approach to chronic, central neuropathic pain in multiple sclerosis, poorly responsive to current conventional medications. tDCS is known to cause long-lasting changes of neuronal excitability at the site of stimulation and in the connected areas in healthy subjects. This led us to hypothesize that pain decrease may be the result of functional plastic changes in brain structures involved in the pathogenesis of chronic neuropathic pain.     

The responsive amygdala: Treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.     

Impaired Glutamatergic Neurotransmission in Migraine With Aura? Evidence by an Input–Output Curves Transcranial Magnetic Stimulation Study

(Headache 2011;51:726‐733) Objective.— An imbalance between activity of inhibitory and facilitatory intracortical circuits could play a central role in migraine etiology. We used input–output curves to achieve further information about intracortical excitability of motor cortex in migraine with aura. Methods.— Input–output curves were measured in the right abductor pollicis brevis muscle at rest in 12 patients suffering from migraine with aura and 8 healthy subjects. Stimuli were delivered at intensity ranging from 100% to 160% of resting motor threshold with 10‐second inter‐stimulus intervals. Seven patients were studied before and during treatment with levetiracetam. Results.— Results showed a greater motor‐evoked potential amplitude in response to increasing intensity of stimuli in patients compared to controls (P < .02). This increased facilitatory effect was abolished by levetiracetam (P < .005). Conclusions.— Our findings support the hypothesis of an interictal cortical hyper‐responsivity in migraine patients that appears to be normalized by levetiracetam. This effect could support the potential therapeutic role of levetiracetam in migraine with aura prevention.