Focal Modulation of the Primary Motor Cortex in Fibromyalgia Using 4×1-Ring High-Definition Transcranial Direct Current Stimulation (HD-tDCS): Immediate and Delayed Analgesic Effects of Cathodal and Anodal Stimulation

Fibromyalgia is a prevalent chronic pain syndrome characterized by altered pain and sensory processing in the central nervous system, which is often refractory to multiple therapeutic approaches. Given previous evidence supporting analgesic properties of noninvasive brain stimulation techniques in this condition, this study examined the effects of a novel, more focal method of transcranial direct current stimulation (tDCS), using the 4×1-ring configuration of high-definition (HD)-tDCS, on overall perceived pain in fibromyalgia patients. In this patient- and assessor-blind, sham-controlled, crossover trial, 18 patients were randomized to undergo single 20-minute sessions of anodal, cathodal, and sham HD-tDCS at 2.0 mA in a counterbalanced fashion. The center electrode was positioned over the left primary motor cortex. Pain scales and sensory testing were assessed before and after each intervention. A finite element method brain model was generated to predict electric field distribution. We found that both active stimulation conditions led to significant reduction in overall perceived pain as compared to sham. This effect occurred immediately after cathodal HD-tDCS and was evident for both anodal and cathodal HD-tDCS 30 minutes after stimulation. Furthermore, active anodal stimulation induced a significant bilateral increase in mechanical detection thresholds. These interventions proved well tolerated in our patient population.Perspective4×1-ring HD-tDCS, a novel noninvasive brain stimulation technique capable of more focal and targeted stimulation, provides significant reduction in overall perceived pain in fibromyalgia patients as compared to sham stimulation, irrespective of current polarity. This technique may have other applications in research and clinical settings, which should be further explored.     

Changes to somatosensory detection and pain thresholds following high frequency repetitive TMS of the motor cortex in individuals suffering from chronic pain

Research has shown that transcranial magnetic stimulation (TMS) results in a transient reduction in the experience of chronic pain. The present research aimed to investigate whether a single session of high frequency TMS is able to change the sensory thresholds of individuals suffering from chronic pain. Detection and pain thresholds for cold and heat sensations were measured before and after 20Hz repetitive TMS (rTMS) administered over the motor cortex. A significant decrease in temperature for cold detection and pain thresholds and a significant increase in temperature for heat pain thresholds were evident following a single session of rTMS. In contrast, no change in detection and pain thresholds was obtained following sham rTMS. The finding that rTMS can have a direct effect on sensory thresholds in individuals suffering from chronic pain has implications for the therapeutic use of rTMS in the relief of chronic pain.     

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.     

Effects of transcranial direct current stimulation on pain perception and working memory

Previous studies have shown that non‐invasive stimulation of the dorsolateral prefrontal cortex (DLPFC) could modulate experimentally induced pain and working memory (WM) in healthy subjects. However, the two aspects have never been assessed concomitantly. The present study was set up to investigate the effects of transcranial direct current stimulation (tDCS) of the DLPFC on thermal pain and WM in the same population of healthy volunteers. In a randomized and balanced order of different sessions separated by 1 week, 20 min of 2 mA anodal, cathodal or sham tDCS were applied to the left or right DLPFC in two separate experiments. Twelve healthy volunteers were enrolled for each stimulated hemisphere. Warm and cold detection thresholds, heat and cold pain thresholds as well as heat pain tolerance thresholds were measured before, during and following tDCS. WM was assessed by a 2‐back task applied once during cortical stimulation. Anodal tDCS of the right DLPFC led to an increase of tolerance to heat pain. The 2‐back task revealed fewer outliers during cathodal tDCS of the left DLPFC. The present data show an involvement of the DLPFC in the processing of pain and WM. There was no correlation between these findings, suggesting that the analgesic effects of cortical stimulation are not associated with cognitive processing. However, this conclusion is difficult to affirm because of some limitations of the study regarding the parameters of stimulation or a ceiling effect of the 2‐back task for instance.     

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.     

Transcranial direct current stimulation (tDCS) for upper limb rehabilitation after stroke: future directions.

Transcranial Direct Current Stimulation (tDCS) is a potentially useful tool to improve upper limb rehabilitation outcomes after stroke, although its effects in this regard have shown to be limited so far. Additional increases in effectiveness of tDCS in upper limb rehabilitation after stroke may for example be achieved by (1) applying a more focal stimulation approach like high definition tDCS (HD-tDCS), (2) involving functional imaging techniques during stimulation to identify target areas more exactly, (3) applying tDCS during Electroencephalography (EEG) (EEG-tDCS), (4) focusing on an effective upper limb rehabilitation strategy as an effective base treatment after stroke. Perhaps going even beyond the application of tDCS and applying alternative stimulation techniques such as transcranial Alternating Current Stimulation (tACS) or transcranial Random Noise Stimulation (tRNS) will further increase effectiveness of upper limb rehabilitation after stroke.     

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.     

Modulation Of Experimental Prolonged Pain and Sensitization Using High-Definition Transcranial Direct Current Stimulation: A Double-Blind,Sham-Controlled Study

High definition transcranial direct current stimulation (HD-tDCS) targeting brain areas involved in pain processing has shown analgesic effects in some chronic pain conditions, but less modulatory effect on mechanical and thermal pain thresholds in asymptomatic subjects. This double-blinded study assessed the HD-tDCS effects on experimental pain and hyperalgesia maintained for several days in healthy participants. Hyperalgesia and pain were assessed during three consecutive days following provocation of experimental pain (nerve growth factor injected into the right-hand muscle) and daily HD-tDCS sessions (20-minutes). Forty subjects were randomly assigned to Active-tDCS targeting primary motor cortex and dorsolateral prefrontal cortex simultaneously or Sham-tDCS. Tactile and pressure pain sensitivity were assessed before and after each HD-tDCS session, as well as the experimentally-induced pain intensity scored on a numerical rating scale (NRS). Subjects were effectively blinded to the type of HD-tDCS protocol. The Active-tDCS did not significantly reduce the NGF-induced NRS pain score (3.5±2.4) compared to Sham-tDCS (3.9±2.0, P > .05) on day 3 and both groups showed similarly NGF-decreased pressure pain threshold in the right hand (P < .001). Comparing Active-tDCS with Sham-tDCS, the manifestation of pressure hyperalgesia was delayed on day 1, and an immediate (pre-HD-tDCS to post-HD-tDCS) reduction in pressure hyperalgesia was found across all days (P < .05).PerspectiveThe non-significant differences between Active-tDCS and Sham-tDCS on experimental prolonged pain and hyperalgesia suggest that HD-tDCS has no effect on moderate persistent experimental pain. The intervention may still have a positive effect in more severe pain conditions, with increased intensity, more widespread distribution, or increased duration and/or involving stronger affective components.     

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.     

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.     

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.     

Stimulations cérébrales non invasives : une nouvelle option thérapeutique pour la douleur chronique ?

Chronic pain care with pharmacological treatment is limited due to efficacy and tolerance. Epidural motor cortex stimulation (MCS) has proven to be effective for pain relief in chronic pain. The aim of these noninvasive stimulation techniques is to obtain the same efficacy while avoiding surgery. Repetitive transcranial magnetic stimulation (rTMS) has an action mode similar to MCS. Targeting the primary motor cortex, it is possible to obtain an analgesic effect that can last for > 2 weeks after each session. Concerning transcranial electrical stimulation, it can rely on direct current (tDCS for transcranial Direct Current Stimulation) or alternating current (tACS for transcranial Alternating Current Stimulation and tRNS for transcranial Random Noise Stimulation). This electrical stimulation leads to a modification of the membrane potential from a large brain zone. The aim of this brief article is to give several recent information concerning the mode of action and the efficacy of these two techniques.     

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.     

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.     

tDCS-Induced Analgesia and Electrical Fields in Pain-Related Neural Networks in Chronic Migraine

Objective.— We investigated in a sham‐controlled trial the analgesic effects of a 4‐week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high‐resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation. Methods.— Thirteen patients with chronic migraine were randomized to receive 10 sessions of active or sham tDCS for 20 minutes with 2 mA over 4 weeks. Data were collected during baseline, treatment and follow‐up. For the tDCS computational analysis, we adapted a high‐resolution individualized model incorporating accurate segmentation of cortical and subcortical structures of interest. Results.— There was a significant interaction term (time vs group) for the main outcome (pain intensity) and for the length of migraine episodes (ANOVA, P < .05 for both analyses). Post‐hoc analysis showed a significant improvement in the follow‐up period for the active tDCS group only. Our computational modeling studies predicted electric current flow in multiple cortical and subcortical regions associated with migraine pathophysiology. Significant electric fields were generated, not only in targeted cortical regions but also in the insula, cingulate cortex, thalamus, and brainstem regions. Conclusions.— Our findings give preliminary evidence that patients with chronic migraine have a positive, but delayed, response to anodal tDCS of the primary motor cortex. These effects may be related to electrical currents induced in pain‐related cortical and subcortical regions.     

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.     

Modulation of central pain mechanisms using high-definition transcranial direct current stimulation: A double-blind,sham-controlled study

Background

The use of high-definition transcranial direct current stimulation (HD-tDCS) has shown analgesic effects in some chronic pain patients, but limited anti-nociceptive effects in healthy asymptomatic subjects.

Methods

This double-blinded sham-controlled study assessed the effects of HD-tDCS applied on three consecutive days on central pain mechanisms in healthy participants with (N = 40) and without (N = 40) prolonged experimental pain induced by intramuscular injection of nerve growth factor into the right hand on Day 1. Participants were randomly assigned to Sham-tDCS (N = 20 with pain, N = 20 without) or Active-tDCS (N = 20 with pain, N = 20 without) targeting simultaneously the primary motor cortex and dorsolateral prefrontal cortex for 20 min with 2 mA stimulation intensity. Central pain mechanisms were assessed by cuff algometry on the legs measuring pressure pain sensitivity, temporal summation of pain (TSP) and conditioned pain modulation (CPM), at baseline and after HD-tDCS on Day 2 and Day 3. Based on subject's assessment of received HD-tDCS (sham or active), they were effectively blinded.

Results

Compared with Sham-tDCS, Active-tDCS did not significantly reduce the average NGF-induced pain intensity. Tonic pain-induced temporal summation at Day 2 and Day 3 was significantly lower in the NGF-pain group under Active-tDCS compared to the pain group with Sham-tDCS (p ≤ 0.05). No significant differences were found in the cuff pressure pain detection/tolerance thresholds or CPM effect across the 3 days of HD-tDCS in any of the four groups.

Conclusion

HD-tDCS reduced the facilitation of TSP caused by tonic pain suggesting that efficacy of HD-tDCS might depend on the presence of sensitized central pain mechanisms.     

Suppression of premotor cortex disrupts motor coding of peripersonal space

Peripersonal space (PPS) representation depends on the activity of a fronto-parietal network including the premotor cortex (PMc) and the posterior parietal cortex (PPc). PPS representation has a direct effect on the motor system: a stimulus activating the PPS around the hand modulates the excitability of hand representation in the primary motor cortex. However, to date, direct information about the involvement of the PMc-PPc network in the motor mapping of sensory events occurring within PPS is lacking. To address this issue, we used a 'perturb-and-measure' paradigm based on the combination of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) techniques. Cathodal tDCS was applied to transiently suppress neural activity in PMc, PPc and primary visual cortex (V1; serving as an active control site); single-pulse TMS was used to induce motor-evoked potentials (MEPs) from hand muscles and so to measure the excitability of the hand motor representation. MEPs were compared when a sound was presented either near the hand or at a distance. In experimental sessions performed after sham-tDCS and after tDCS over the control area V1, we found a spatially dependent modulation of the hand motor representation: sounds presented near the hand induced an inhibitory motor response as compared to sounds presented far apart. Critically, this effect was selectively abolished after tDCS suppression of neural activity in PMc, but not when perturbing the activity of PPc. These findings suggest that PMc has a critical role in mapping sensory representations of space onto the motor system.     

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.