Inhibitory effect of voluntary movement preparation on cutaneous heat pain and laser-evoked potentials

In our study, preparation of voluntary movement was used to physiologically activate the motor cortex areas and the effect of this activation on CO(2) laser-evoked potentials (LEPs) was explored. LEPs were recorded from 31 scalp electrodes in 10 healthy subjects after painful stimulation of the right C6-C7 skin dermatomes. LEP stimuli were delivered in the time interval between a visual warning stimulus followed after 1 s. by an imperative stimulus. The imperative stimulus triggered: (i) no task in the baseline condition (Pain); (ii) flexion-extension movements of the second finger of the right hand in the movement condition (Pain + Movement); (iii) cognitive task (mathematic computation) in the distraction condition (Pain + Cognition). The experimental conditions were also repeated during application of laser stimuli on the left C6-C7 skin dermatomes. Compared with the baseline condition (no task required), during preparation of right-hand voluntary movement there was a significant reduction in LEP amplitude and subjective pain rating after right- but not after left-hand stimulation, which suggests that the observed effect cannot be attributed to a nonspecific reduction in attention toward painful stimulus. During preparation of a cognitive task, LEP amplitude was reduced compared to baseline. Our results represent the first neurophysiological suggestion that physiological activation of the motor cortex, occurring during movement preparation, inhibits cortical pain processing by a centrifugal mechanism.     

Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain

OBJECTIVE: Drug resistant neurogenic pain can be relieved by repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. This study was designed to assess the influence of pain origin, pain site, and sensory loss on rTMS efficacy. PATIENTS AND METHODS: Sixty right handed patients were included, suffering from intractable pain secondary to one of the following types of lesion: thalamic stroke, brainstem stroke, spinal cord lesion, brachial plexus lesion, or trigeminal nerve lesion. The pain predominated unilaterally in the face, the upper limb, or the lower limb. The thermal sensory thresholds were measured within the painful zone and were found to be highly or moderately elevated. Finally, the pain level was scored on a visual analogue scale before and after a 20 minute session of "real" or "sham" 10 Hz rTMS over the side of the motor cortex corresponding to the hand on the painful side, even if the pain was not experienced in the hand itself. RESULTS: and discussion: The percentage pain reduction was significantly greater following real than sham rTMS (-22.9% v -7.8%, p = 0.0002), confirming that motor cortex rTMS was able to induce antalgic effects. These effects were significantly influenced by the origin and the site of pain. For pain origin, results were worse in patients with brainstem stroke, whatever the site of pain. This was consistent with a descending modulation within the brainstem, triggered by the motor corticothalamic output. For pain site, better results were obtained for facial pain, although stimulation was targeted on the hand cortical area. Thus, in contrast to implanted stimulation, the target for rTMS procedure in pain control may not be the area corresponding to the painful zone but an adjacent one. Across representation plasticity of cortical areas resulting from deafferentation could explain this discrepancy. Finally, the degree of sensory loss did not interfere with pain origin or pain site regarding rTMS effects. CONCLUSION: Motor cortex rTMS was found to result in a significant but transient relief of chronic pain, influenced by pain origin and pain site. These parameters should be taken into account in any further study of rTMS application in chronic pain control.     

Dissociation between cutaneous silent period and laser evoked potentials in assessing neuropathic pain

In this study we investigate whether the cutaneous silent period (CSP)—an inhibitory response evoked in hand muscles by painful digital nerve stimulation—is useful for assessing nociceptive pathway function in patients with neuropathic pain. In 40 patients with peripheral neuropathy (21 without and 19 with neuropathic pain) we recorded the CSP in the abductor digiti minimi after fifth digit stimulation and also recorded laser evoked potentials (LEPs) after stimulation applied to the ulnar territory of the hand. Although the LEP amplitude was significantly lower in patients with pain than in those without (P < 0.005), the CSP duration did not differ between groups (P > 0.50). Pain intensity correlated significantly with LEP amplitudes (P < 0.005) but not with CSP duration (P > 0.5). Our findings indicate that the CSP is not useful for assessing nociceptive pathway function in patients with neuropathic pain. Muscle Nerve, 2008     

Cortical inhibition of laser pain and laser‐evoked potentials by non‐nociceptive somatosensory input

Although the inhibitory action that tactile stimuli can have on pain is well documented, the precise timing of the interaction between the painful and non‐painful stimuli in the central nervous system is unclear. The aim of this study was to investigate this issue by measuring the timing of the amplitude modulation of laser evoked potentials (LEPs) due to conditioning non‐painful stimuli. LEPs were recorded from 31 scalp electrodes in 10 healthy subjects after painful stimulation of the right arm (C6–C7 dermatomes). Non‐painful electrical stimuli were applied by ring electrodes on the second and third finger of the right hand. Electrical stimuli were delivered at +50, +150, +200 and +250 ms interstimulus intervals (ISIs) after the laser pulses. LEPs obtained without any conditioning stimulation were used as a baseline. As compared to the baseline, non‐painful electrical stimulation reduced the amplitude of the vertex N2/P2 LEP component and the laser pain rating when electrical stimuli followed the laser pulses only at +150 and +200 ms ISIs. As at these ISIs the collision between the non‐painful and painful input is likely to take place at the cortical level, we can conclude that the late processing of painful (thermal) stimuli is partially inhibited by the processing of non‐painful (cutaneous) stimuli within the cerebral cortex. Moreover, our results do not provide evidence that non‐painful inputs can inhibit pain at a lower level, including the spinal cord.     

Nociceptive pathway function is normal in cervical dystonia: a study using laser-evoked potentials

Cervical dystonia (CD) is often associated with pain in the neck muscles, though the mechanisms underlying pain in this condition are still largely unknown. The aim of this study was to assess laser pain rating and CO(2) laser-evoked potentials (LEPs) in CD patients with pain in the posterior neck region. We assessed the N2/P2 LEP complex and laser pain rating in a group of 20 CD patients and in 21 normal subjects. In 11 of the 20 CD patients (group I), the N2/P2 complex was recorded after stimulation of the skin overlying the right and left deltoid muscles (painless and non-dystonic). In the remaining nine CD patients (group II), the N2/P2 complex was recorded after stimulation of the skin over the splenius capitis muscle (painful and dystonic) and after stimulation of the skin overlying the contralateral splenius muscle (painless and non-dystonic). In group I patients, the N2/P2 LEP amplitude and laser pain rating after stimulation of both shoulders did not differ significantly from those obtained in normal subjects. Similarly, in group II patients, the N2/P2 LEP amplitude and laser pain rating after stimulation of the painful and dystonic splenius capitis muscle did not differ significantly from those obtained from either the contralateral painless, non-dystonic splenius capitis or normal subjects. The results of this study demonstrate that cutaneous nociceptive pathway function in CD patients is normal, thereby indicating that muscle pain in CD is not associated with any central sensitization of nociceptive inputs in either painful (dystonic) or non-painful (non-dystonic) body areas.     

Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain

BACKGROUND AND OBJECTIVE: A single session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex had been reported to produce short term relief of some types of chronic pain. The present study investigated whether five consecutive days of rTMS would lead to longer lasting pain relief in unilateral chronic intractable neuropathic pain. PATIENTS AND METHODS: Forty eight patients with therapy resistant chronic unilateral pain syndromes (24 each with trigeminal neuralgia (TGN) and post-stroke pain syndrome (PSP)) participated. Fourteen from each group received 10 minutes real rTMS over the hand area of motor cortex (20 Hz, 10x10 s trains, intensity 80% of motor threshold) every day for five consecutive days. The remaining patients received sham stimulation. Pain was assessed using a visual analogue scale (VAS) and the Leeds assessment of neuropathic symptoms and signs (LANSS) scale, before, after the first, fourth, and fifth sessions, and two weeks after the last session. RESULTS: No significant differences were found in basal pain ratings between patients receiving real- and sham-rTMS. However, a two factor ANOVA revealed a significant "+/- TMS" x "time" interaction indicating that real and sham rTMS had different effects on the VAS and LANSS scales. Post hoc testing showed that in both groups of patients, real-rTMS led to a greater improvement in scales than sham-rTMS, evident even two weeks after the end of the treatment. No patient experienced adverse effects. CONCLUSION: These results confirm that five daily sessions of rTMS over motor cortex can produce longlasting pain relief in patients with TGN or PSP.     

Repetitive transcranial magnetic stimulation for the treatment of chronic pain - a pilot study

Invasive electrical stimulation of the motor cortex has been reported to be of therapeutic value in pain control. We were interested whether noninvasive repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex might also act beneficially. Twelve patients with therapy-resistant chronic pain syndromes (mean age 51.3 +/- 12.6, 6 males) were included in a pilot study. They were treated with rTMS of the corresponding motor cortex area for 20 min (20 Hz, 20 x 2 s trains, intensity 80% of motor threshold) and sham stimulation (sequence-controlled cross-over design). Some of the patients (6/6) had an analgesic effect, but for the whole group, the difference between active and sham stimulation did not reach a level of significance (active rTMS: mean VAS reduction -4.0 +/- 15.6%; sham rTMS: -2.3 +/- 8.8%). Further studies using different rTMS stimulation parameters (duration and frequency of rTMS) or stimulation sites (e.g. anterior cingulate gyrus) are strongly encouraged.     

Muscular pain in Parkinson's disease and nociceptive processing assessed with CO2 laser‐evoked potentials

Muscular pain is the most frequent kind of nondystonic pain associated with Parkinson's disease (PD). It might be related not only to peripheral factors but also to an abnormal nociceptive input processing in the central nervous system. To test this hypothesis, we recorded CO₂ laser‐evoked potentials (LEPs) in response to shoulder stimulation (skin over deltoid muscle) in 11 hemiparkinsonian PD patients complaining of muscular pain in the shoulder (ipsilateral to motor symptoms) and compared the results with those obtained in 12 pain‐free PD patients with hemiparkinson and in 11 normal subjects. N2/P2 LEP, which is thought to originate from the cingulate cortex and insula, was significantly lower in amplitude in both groups of PD patients than in controls, regardless of the clinically affected body side. In both groups of PD patients, no significant correlation was observed between the severity of motor symptoms and N2/P2 amplitude abnormalities. In PD patients with muscular pain, the N2/P2 amplitude obtained following stimulation of the painful shoulder was significantly reduced compared with that obtained in response to nonpainful shoulder stimulation and compared with the values obtained in pain‐free PD patients. No significant correlation was observed between the intensity of muscular pain and N2/P2 amplitude abnormalities in this group of PD patients. These results suggest abnormal nociceptive input processing in PD, which appears to be independent of clinical expression of parkinsonian motor signs. These alterations are more evident in the presence of muscular pain. © 2010 Movement Disorder Society     

Modulation of laser-evoked potentials and pain perception by transcutaneous electrical nerve stimulation (TENS): A placebo-controlled study in healthy volunteers

ObjectiveTo investigate the effects of transcutaneous electrical nerve stimulation (TENS) on brain nociceptive responses (laser-evoked potentials, LEPs) and pain perception.MethodsTwenty healthy subjects were included. Nociceptive CO₂-laser pulses were sequentially delivered to the dorsum of both feet. The amplitude of LEPs and nociceptive thresholds were collected in three consecutive conditions: T1: “sham” TENS (2 Hz/low-intensity) positioned heterotopically, over the left thigh; T2: “active” TENS (120 Hz/low-intensity) applied homotopically, over the left common peroneal nerve; and T3: “sham” TENS (replication of condition T1).ResultsCompared with “sham” TENS, “active” TENS significantly decreased the LEPs amplitude. This effect was observed exclusively when “active” TENS was applied ipsilaterally to the painful stimulus. Nociceptive thresholds increased with sessions in both limbs, but the increase observed during the “active” condition of TENS (T2) exceeded significantly that observed during the condition T3 only on the foot ipsilateral to TENS.ConclusionsCompared with a credible placebo TENS, high-frequency TENS induced a significant attenuation of both the acute pain and LEPs induced by noxious stimuli applied on the same dermatome.SignificanceThis modulation of subjective and objective concomitants of pain processing reflects a real neurophysiological TENS-related effect on nociceptive transmission.     

High-frequency rTMS over the dorsolateral prefrontal cortex on chronic and provoked pain: A systematic review and meta-analysis

BackgroundHigh-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain.Objectives/MethodsIn this study, a meta-analysis was conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on both chronic and provoked pain.ResultsA total of 626 studies were identified in a systematic search. Twenty-six eligible studies were included for the quantitative review, among which 17 modulated chronic pain and the remaining investigated the influence on provoked pain. The left side DLPFC was uniformly targeted in the chronic pain studies. While our data identified no overall effect of TMS across chronic pain conditions, there was a significant short-term analgesia in neuropathic pain conditions only (SMD = −0.87). In terms of long-lasting analgesia, there was an overall pain reduction in the midterm (SMD = −0.53, 24.6 days average) and long term (SMD = −0.63, 3 months average) post DLPFC stimulation, although these effects were not observed within specific chronic pain conditions. Surprisingly, the number of sessions was demonstrated to have no impact on rTMS analgesia. In the analysis of provoked pain, our data also indicated a significant analgesic effect following HF-rTMS over the DLPFC (SMD = −0.73). Importantly, we identified a publication bias in the studies of provoked pain but not for chronic pain conditions.ConclusionsOverall, our findings support that HF-DLPFC stimulation is able to induce an analgesic effect in chronic pain and in response to provoked pain. These results highlight the potential of DLPFC-rTMS in the management of certain chronic pain conditions and future directions are discussed to enhance the potential long-term analgesic effects.     

重复经颅磁刺激治疗慢性神经病理性疼痛

目的探讨重复经颅磁刺激（rTMS）对慢性神经病理性疼痛的疗效和安全性。方法回顾性分析4例慢性神经病理性疼痛病人的资料,其中丘脑痛3例,臂丛神经撕脱伤后疼痛1例,均经正规药物治疗效果欠佳,给予运动皮质10Hz的rTMS（1000次刺激）治疗,每个疗程5d,共3个疗程。分别于治疗前、每个疗程后以及全部疗程结束后1个月、6个月和1年采用视觉模拟疼痛评分（VAS）、汉密尔顿抑郁评分（HAMD）和汉密尔顿焦虑评分（HAMA）来评估疗效。结果全部疗程结束后,疗效满意3例,疗效差l例。疗效满意病人中,随访1年后复发2例。副作用为治疗期间头面部轻度疼痛1例。结论rTMS对部分慢性神经病理性疼痛安全有效．尤其是面部和肢体疼痛的病人。但其疗效不持久,可作为运动皮质电刺激的测试方法。     

Decreased sensory cortical excitability after 1 Hz rTMS over the ipsilateral primary motor cortex.

OBJECTIVES: To study changes in the excitability of the sensory cortex by repetitive transcranial magnetic stimulation (rTMS) in humans. METHODS: Somatosensory evoked potentials (SEPs) and antidromic sensory nerve action potentials (SNAPs) were elicited by right median nerve stimulation at the wrist before and after low frequency (1 Hz) rTMS over the left motor cortex, lateral premotor cortex, sensory cortex, and also after sham stimulation. The intensity of rTMS was fixed at 1.1 times the active motor threshold at the hand area of motor cortex. RESULTS: N20 peak (N20p)-P25 and P25-N33 amplitudes were suppressed after rTMS over the motor cortex, whereas the N20 onset (N20o)-N20p and SNAP amplitudes were not affected. They recovered to the baseline about 100 min after the rTMS. rTMS over the premotor cortex or sensory cortex or sham stimulation had no suppressive effect on SEPs. CONCLUSIONS: The reduction of N20p-P25 and P25-N33 components without any changes of N20o-N20p amplitude suggests that the suppression occurs in the sensory cortex. rTMS (1 Hz) of the motor cortex induces a long-lasting suppression of the ipsilateral sensory cortex even at an intensity as low as 1.1 times the active motor threshold, probably via cortico-cortical pathways between motor and sensory cortex.     

Abnormal nociceptive processing occurs centrally and not peripherally in pain-free Parkinson disease patients: A study with laser-evoked potentials

BackgroundSeveral studies documented abnormal nociceptive processing in PD patients. Pain central pathways are accessible by laser-evoked potentials (LEPs). LEPs recording show a N2/P2 complex mostly generated by the anterior cingulate cortex, preceded by an earlier negative component (N1), originating from the opercular cortex. Previous work demonstrated N2/P2 amplitude reduction in PD patients and suggested a centrally-acting pathomechanism for the genesis of pain. However, since a peripheral deafferentation has been recently demonstrated in PD, it is not clear if such LEP abnormalities reflect a mechanism acting centrally or not.ObjectiveTo assess whether abnormalities of nociceptive inputs occur at central and/or peripheral level in pain-free PD patients with hemiparkinson using Nd:YAP LEPs.MethodsWe recorded scalp Nd:YAP-LEPs to hand stimulation in 13 pain-free patients with unilateral PD and in 13 healthy subjects. Additionally, we collected laser pain-rating in both groups.ResultsPD patients and normal subjects showed comparable N1, N2 and P2 latencies. The N2/P2 amplitude was significantly lower in PD patients than in controls, regardless of the clinically affected side, whereas the N1/P1 amplitude was not different. PD patients had higher pain-rating, indicative of hyperalgesia.ConclusionsThese findings demonstrate that in the PD patients the abnormal processing of pain stimuli occurs at central rather than peripheral level. The co-existence of hyperalgesia and reduced amplitude of the N2/P2 complex, in spite of a normal N1/P1 component, suggests an imbalance between the medial and lateral pain systems. Such a dissociation might explain the genesis of central pain in PD.     

Non pharmacological treatment for neuropathic pain: Invasive and non-invasive cortical stimulation

The use of medications in chronic neuropathic pain may be limited with regard to efficacy and tolerance. Therefore, non-pharmacological approaches, using electrical stimulation of the cortex has been proposed as an alternative. First, in the early nineties, surgically-implanted epidural motor cortex stimulation (EMCS) was proven to be effective to relieve refractory neuropathic pain. Later, non-invasive stimulation techniques were found to produce similar analgesic effects, at least by means of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1). Following “high-frequency” rTMS (e.g., stimulation frequency ranging from 5 to 20 Hz) delivered to the precentral gyrus (e.g., M1 region), it is possible to obtain an analgesic effect via the modulation of several remote brain regions involved in nociceptive information processing or control. This pain reduction can last for weeks beyond the time of the stimulation, especially if repeated sessions are performed, probably related to processes of long-term synaptic plasticity. Transcranial direct current stimulation (tDCS), another form of transcranial stimulation, using low-intensity electrical currents, generally delivered by a pair of large electrodes, has also shown some efficacy to improve patients with chronic pain syndromes. The mechanism of action of tDCS differs from that of EMCS and rTMS, but the cortical target is the same, which is M1. Although the level of evidence of therapeutic efficacy in the context of neuropathic pain is lower for tDCS than for rTMS, interesting perspectives are opened by using at-home tDCS protocols for long-term management. Now, there is a scientific basis for recommending both EMCS and rTMS of M1 to treat refractory chronic neuropathic pain, but their application in clinical practice remains limited due to practical and regulatory issues.     

The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain.

Chronic motor cortex stimulation using implanted epidural stimulation was proposed to treat chronic, drug-resistant neuropathic pain. Various studies showed that repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex could also relieve neuropathic pain, at least partially and transiently. Controlled rTMS studies with other cortical targets, such as the dorsolateral prefrontal cortex, are in waiting. The mechanisms of action of rTMS on chronic pain are mostly unknown. The changes induced by rTMS in neural activities may occur at the stimulated cortical site as well as in remote structures along functional anatomical connections. Compared to chronic implanted procedure, the main limitation of rTMS application is the short duration of clinical effects. Repeated daily rTMS sessions have proved some efficacy to induce long-lasting pain relief that could have therapeutic potential. However, rTMS-induced analgesia varies with the site and parameters of stimulation, in particular the stimulus rate. The efficacious rTMS parameters could differ from those used in chronic epidural stimulation. Differences in the pattern of the current fields respectively induced in the brain by these two techniques might explain this finding. Actually, stimulation parameters remain to be optimised and clinical efficacy to be confirmed by multicentre randomised trials, before considering rTMS as therapeutic tool for patients with chronic pain in neurological practice.     

Functional assessment of A delta and C fibers in patients with Fabry's disease

The pathophysiology of neuropathic pain in Fabry's disease (FD) is still largely unknown. Seven FD patients were studied by laser evoked potentials (LEPs) to assess the function of the A delta and C fibers. Laser pulses were delivered on the skin of the hand and perioral region at painful intensity to record LEPs related to A delta-fiber inputs and at nonpainful intensity to obtain LEPs related to C-fiber inputs. When the perioral region was stimulated, a vertex positive component was recorded with a mean latency of 260.3 ms and 376 ms after A delta- and C-fiber stimulation, respectively. The mean A delta-LEP amplitude was significantly lower in FD patients (N1/P1 mean values were 2.8 microV and 4.5 microV after hand and face stimulation, respectively, compared to 4 microV and 8.9 microV for controls; N2/P2 mean values were 8.2 microV and 11.1 microV after hand and face stimulation, respectively, and 16.7 microV and 22.3 microV in controls). Unlike the healthy subjects, 6 FD patients, suffering from neuropathic pain, showed a late positive potential related to C-fiber function (mean latency, 377.1 ms) also after facial stimulation at painful intensity, suggesting a relative overflow of C-fiber input, which may be relevant in the pathophysiology of pain in this disease.     

Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain — A pilot double-blind,randomized cross-over study

ObjectivesPeripheral neuropathic pain (pNeP) is prevalent, and current treatments, including drugs and motor cortex repetitive transcranial magnetic stimulation (rTMS) leave a substantial proportion of patients with suboptimal pain relief.MethodsWe explored the intensity and short-term duration of the analgesic effects produced in pNeP patients by 5 days of neuronavigated deep rTMS targeting the posterior superior insula (PSI) with a double-cone coil in a sham-controlled randomized cross-over trial.ResultsThirty-one pNeP patients received induction series of five active or sham consecutive sessions of daily deep-rTMS to the PSI in a randomized sequence, with a washout period of at least 21 days between series. The primary outcome [number of responders (>50% pain intensity reduction from baseline in a numerical rating scale ranging from 0 to 10)] was significantly higher after real (58.1%) compared to sham (19.4%) stimulation (p = 0.002). The number needed to treat was 2.6, and the effect size was 0.97 [95% CI (0.6; 1.3)]. One week after the 5th stimulation day, pain scores were no longer different between groups, and no difference in neuropathic pain characteristics and interference with daily living were present. No major side effects occurred, and milder adverse events (i.e., short-lived headaches after stimulation) were reported in both groups. Blinding was effective, and analgesic effects were not affected by sequence of the stimulation series (active-first or sham-first), age, sex or pain duration of participants.DiscussionPSI deep-rTMS was safe in refractory pNeP and was able to provide significant pain intensity reduction after a five-day induction series of treatments. Post-hoc assessment of neuronavigation targeting confirmed deep-rTMS was delivered within the boundaries of the PSI in all participants.ConclusionPSI deep-rTMS provided significant pain relief during 5-day induction sessions compared to sham stimulation.     

Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex.

The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body, by means of surgically-implanted epidural electrodes is a validated therapeutical strategy to control medication-resistant neurogenic pain. Repetitive transcranial magnetic stimulation (rTMS) permits to stimulate non-invasively and precisely the motor cortex. We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a 'real' or a 'sham' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy. We studied the effects of rTMS on pain level assessed on a 0-10 visual analogue scale from day 1 to day 12 following the rTMS session. A significant pain decrease was observed up to 8 days after the 'real' rTMS session. This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex.     

Paired Acute Invasive/Non-invasive Stimulation (PAINS) study: A phase I/II randomized,sham-controlled crossover trial in chronic neuropathic pain

BackgroundDorsal root ganglion (DRG) stimulation, an invasive method of neuromodulation, and transcranial direct current stimulation (tDCS), a non-invasive method of altering cortical excitability, have both proven effective in relieving chronic pain.ObjectiveWe employed a randomized, sham-controlled crossover study design to investigate whether single-session tDCS would have an additive therapeutic effect alongside DRG stimulation (DRGS) in the treatment of chronic pain.MethodsSixteen neuropathic pain patients who were previously implanted with DRG stimulators were recruited. Baseline pain scores were established with DRGS-OFF. Pain scores were then recorded with DRGS-ON, after paired sham tDCS stimulation, and after paired active anodal tDCS (a-tDCS) stimulation. For active tDCS, patients were randomized to ‘MEG (magnetoencephalography) localized’ tDCS or contralateral motor cortex (M1) tDCS for 30 min. EEG recordings and evaluations of tDCS adverse effects were also collected.ResultsAll participants reported the interventions to be tolerable with no significant adverse effects during the session. Paired DRGS/active tDCS resulted in a significant reduction in pain scores compared to paired DRGS-ON/sham tDCS or DRGS alone. There was no difference in the additive effect of M1 vs. MEG-localized tDCS. Significant augmentation of beta activity was observed between DRGS-OFF and DRGS-ON conditions, as well as between paired DRGS-ON/sham tDCS and paired DRGS-ON/active tDCS.ConclusionOur results indicate that a single session of tDCS alongside DRGS is safe and can significantly reduce pain acutely in neuropathic pain patients. Paired invasive/non-invasive neuromodulation is a promising new treatment strategy for pain management and should be evaluated further to assess long-term benefits.     

Analgesic Effects of Repetitive Transcranial Magnetic Stimulation at Different Stimulus Parameters for Neuropathic Pain: A Randomized Study

ObjectivesThe aim of the present study was to investigate the analgesic effects of repetitive transcranial magnetic stimulation over the primary motor cortex (M1-rTMS) using different stimulation parameters to explore the optimal stimulus condition for treating neuropathic pain.Materials and MethodsWe conducted a randomized, blinded, crossover exploratory study. Four single sessions of M1-rTMS at different parameters were administered in random order. The tested stimulation conditions were as follows: 5-Hz with 500 pulses per session, 10-Hz with 500 pulses per session, 10-Hz with 2000 pulses per session, and sham stimulation. Analgesic effects were assessed by determining the visual analog scale (VAS) pain intensity score and Short-Form McGill Pain Questionnaire 2 (SF-MPQ2) score immediately before and immediately after intervention.ResultsWe enrolled 22 adults (age: 59.8 ± 12.1 years) with intractable neuropathic pain. Linear-effects models showed significant effects of the stimulation condition on changes in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.01). Tukey multiple comparison tests revealed that 10-Hz rTMS with 2000 pulses provided better pain relief than sham stimulation, with greater decreases in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.02).ConclusionsThe results of this study suggest that high-dose stimulation (specifically, 10-Hz rTMS at 2000 pulses) is more effective than lower-dose stimulation for treating neuropathic pain.