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.     

Efficacy and tolerability in patients with chronic facial pain of two consecutive treatment periods of rTMS applied over the facial motor cortex,using protocols differing in stimulation frequency,duration, and train pattern

ObjectiveWe conducted an open-label cross-over study assessing the global effect of two high-frequency protocols of electric-field navigated repetitive transcranial magnetic stimulation (rTMS) targeted to functional facial motor cortex and comparing their efficacy and tolerability in patients with chronic facial pain. Outcome predictors were also assessed.MethodsWe randomized twenty consecutive patients with chronic facial pain (post-traumatic trigeminal neuropathic pain, n=14; persistent idiopathic facial pain, n=4; secondary trigeminal neuralgia, n=2) to receive two distinct 5-day rTMS interventions (10Hz, 2400 pulses and 20Hz, 3600 pulses) separated by six weeks. The target area was assessed by mapping of lower face representation. The primary endpoint was the change in weekly mean of pain intensity (numeric rating scale, NRS) between the baseline and therapy week (1^st week), and follow-up weeks (2^nd and 3^rd weeks) for each rTMS intervention. Response was defined using a combination scale including the patient's global impression of change and continuance with maintenance treatment.ResultsOverall, pain intensity NRS decreased from 7.4 at baseline to 5.9 ten weeks later, after the second rTMS intervention (p=0.009). The repetition of the treatment had a significant effect (F=4.983, p=0.043) indicating that the NRS scores are lower during the second four weeks period. Eight (40%) patients were responders, 4 (20%) exhibited a modest effect, 4 (20%) displayed no effect, and 4 (20%) experienced worsening of pain. High disability and high pain intensity (>7) predicted a better outcome (p=0.043 and p=0.045). Female gender, shorter duration of pain and low Beck Anxiety Inventory scores showed a trend towards a better outcome (p=0.052, 0.060 and 0.055, respectively).ConclusionsHigh-frequency rTMS targeted to face M1 alleviates treatment resistant chronic facial pain. Repeated treatment improves the analgesic effect. A protocol with higher frequency (above 10Hz), longer session duration (more than 20 minutes) and higher number of pulses (above 2400 pulses/session) did not improve the outcome. The results support early consideration of rTMS.     

Long-term treatment of chronic orofacial,pudendal, and central neuropathic limb pain with repetitive transcranial magnetic stimulation of the motor cortex

ObjectiveTo assess the long-term analgesic effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with chronic pain syndrome.MethodsThe study included 57 patients (orofacial pain, n = 26, pudendal neuralgia, n = 18, and neuropathic limb pain, n = 13) with an “induction phase” of 12 daily rTMS sessions for 3 weeks, followed by a “maintenance phase” of bi-monthly sessions for the next five months.ResultsAll pain measures significantly decreased from baseline to the end of the induction phase. Analgesic response, defined as pain intensity decrease ≥ 30% compared to baseline, was observed in 39 patients (68%), who could be differentiated from non-responders from the 7th rTMS session. At the end of the maintenance phase (D180), 27 patients (47%) were still responders. Anxio-depressive symptoms and quality of life also improved. The analgesic response at the end of the induction phase was associated with lower pain score at baseline, and the response at the end of the maintenance phase was associated with lower anxio-depressive score at baseline.ConclusionThe analgesic efficacy of motor cortex rTMS can be maintained in the long term in various chronic pain conditions. Patients with high pain level and severe anxio-depressive symptoms may have a less favorable profile to respond to the procedure.SignificanceThe overall impact of rTMS treatment on daily life requires a multidimensional evaluation that goes beyond the analgesic effect that can be achieved.     

Pilot study of repetitive transcranial magnetic stimulation in patients with chemotherapy-induced peripheral neuropathy

ObjectiveChemotherapy-induced peripheral neuropathy (CIPN) is one of the intractable long-term side effects of anticancer medications and results in pain and dysesthesia. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide effective relief for intractable neuropathic pain. The objective of this study was to investigate the effects of rTMS treatment on CIPN in cancer patients.Materials and methodsEleven female patients with breast cancer or gynecologic cancer (mean age 64.8 [standard deviation 7.8]) who had neuropathic pain and/or peripheral sensory neuropathy, with a minimum two grade severity based on the scale of the National Cancer Institutes’ Common Terminology Criteria for Adverse Events (version 4.0) were enrolled. Patients received rTMS (5-Hz; 500 pulses/session; figure-8 coil) on their primary motor cortex corresponding to the target extremity. The intensity of pain and dysesthesia for all extremities was evaluated using a visual analog scale for pain, dysesthesia, and the Japanese version of the short-form McGill Pain Questionnaire 2 (SFMPQ2).ResultsrTMS for target extremity significantly decreased the visual analog scale of pain and dysesthesia. The intensity of pain measured by the SFMPQ2 was also decreased in the target extremity. Regarding non-target extremities, only dysesthesia significantly decreased as a result of rTMS. No adverse events were observed.ConclusionThis is an initial report demonstrating the potential of rTMS for the treatment of CIPN. We suggest rTMS could be potentially beneficial and effective as a treatment for pain and dysesthesia in patients with CIPN.     

Fast Left Prefrontal rTMS Reduces Post-Gastric Bypass Surgery Pain: Findings From a Large-Scale,Double-Blind,Sham-Controlled Clinical Trial

BackgroundA single session of left prefrontal rTMS has been shown to have analgesic effects, and to reduce post-operative morphine use. We sought to test these findings in a larger sample, and try and see if multiple sessions had additive analgesic benefit.Methods108 patients undergoing laparoscopic gastric bypass surgery received two sessions of 10 Hz rTMS (110% of motor threshold) over the left dorsolateral prefrontal cortex (one immediately following surgery and one 4 h later). Participants were randomly assigned to receive 2 sessions of real rTMS, 2 sessions of sham, 1 real then 1 sham, or 1 sham then 1 real rTMS treatments. Patients and study staff were blind to rTMS conditions.ResultsUnlike previous rTMS trials for post-operative pain, no differences emerged between groups with respect to total patient-controlled analgesia usage (IV hydromorphone). However, despite no difference in IV analgesic usage, subjects that received 2 real rTMS sessions rated both the affective and sensory dimensions of their pain significantly lower than those in the sham–sham group at several time points during the post-surgical/post-rTMS period.ConclusionsThis study suggests that left prefrontal rTMS may produce significant analgesic effects in the perioperative setting. However, further work is needed to understand this effect and attempt to make it clinically useful in light of the lack of effect on PCA hydromorphone use.     

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。     

Effects of Anodal Transcranial Direct Current Stimulation on the Primary Motor Cortex in Women With Fibromyalgia: A Randomized,Triple-Blind Clinical Trial

ObjectivesThe aim of this study was to analyze the effects of ten sessions of active transcranial direct current stimulation transcranial direct current stimulation (tDCS) (2 mA) with 13:20:13 stimulation at M1 in women with fibromyalgia (FM). To the best of our knowledge, this is the first article that uses this protocol in patients with FM. The main hypothesis is that the protocol would be effective in decreasing pain and that the results would last for up to 90 days.Materials and MethodsThis study was a randomized clinical trial with 35 women with FM divided into two groups, active tDCS group and sham tDCS group. A conventional tDCS device was used to deliver 2 mA for 13 minutes, with a 20-minute break followed by a further 13 minutes of stimulation for ten sessions. The anodal stimulus was in the left primary motor cortex M1 region. The primary outcome was a change in the visual analog scale and the Survey of Pain Attitudes pain score at the end of treatment, after 30 days, and 90 days after the end of treatment. Secondary outcomes included changes in the Fibromyalgia Impact Questionnaire, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, World Health Organization's Quality of Life Questionnaire, and Fatigue Assessment Scale. The Research Ethics Committee of the Centro Universitário da Grande Dourados under registration number Certificado de Apresentação de Apreciação Ética approved this research: 36444920.5.0000.5159. The study was registered in The Brazilian Registry of Clinical Trials with the identifier RBR-8wc8rjq.ResultsThe active tDCS group showed improvement in pain after ten sessions (p < 0.001), after 30 days (p < 0.01), and after 90 days (p < 0.001) compared with sham tDCS. In addition, improvement in quality of life (QoL) and fatigue was observed in the active tDCS group.ConclusionThe results of this study suggest that active tDCS with an intensity of 2 mA for ten sessions was effective in decreasing pain and fatigue and improving QoL in patients with FM.     

Wireless Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Trigeminal Pain: A Single Center Experience

IntroductionSubcutaneous trigeminal nerve field stimulation (sTNFS) is a neuromodulatory treatment for neuropathic trigeminal pain with the ability to reduce the intensity and frequency of pain attacks. However, hardware issues including lead migration, skin erosion, infection, so-called pocket pain at the site of the implanted neurostimulator are reported. Implantable wireless neurostimulation technology promises not only an even less invasive sTNFS treatment and thinner and more flexible electrodes better suited for facial implants, but also provides further advantages such as lack of an implantable neurostimulator and 3T magnetic resonance imaging compatibility.Material and MethodsAll patients who had received trial stimulation with a partially implantable sTNFS system were analyzed for ICHD-3 (3rd edition of the International Classification of Headache Disorders) diagnosis, success of trial stimulation, pre- and postoperative pain intensity, frequency of attacks, complications, and side-effects of sTNFS.ResultsAll patients (N = 3) responded to sTNFS (≥50% pain reduction) during the trial period. According to ICHD-3, N = 2 of the patients were classified with trigeminal neuralgia (TN) with concomitant persistent facial pain and N = 1 patient with multiple sclerosis associated TN. The time of the test period was 44 ± 31.24 days (mean ± SD). The average daily duration of stimulation per patient amounted 2.5 ± 2.2 hours (range 1–5). The pain intensity (defined on a visual analog scale) was reduced by 80% ± 17% (mean ± SD). Reduction or cessation in pain medication was observed in all patients. No surgical complications occurred in the long-term follow-up period of 18.84 ± 6 (mean ± SD) months.ConclusionThe partially implantable sTNFS device seems to be safe, effective, and reliable. Compared to conventional devices, the equipment is not limited to the length of trial stimulation. Furthermore, the daily stimulation duration was much shorter compared to previous reports.     

Evaluation of the Efficacy of Musical Vibroacupuncture in Pain Relief: A Randomized Controlled Pilot Study

ObjectivesTo investigate if skin vibration employing consonant frequencies emitted by skin transducers attached to a combination of acupuncture points and according to musical harmony (musical chord) produces more significant pain relief compared to just a single frequency.Materials and MethodsSkin vibrostimulation produced by five electromagnet transducers was applied at five acupoints traditionally used to pain relief and anxiety in 13 pain-free healthy volunteers using the cold pressor test (CPT). The study consisted of three randomized sessions conducted on alternate days, with participants receiving either simultaneous frequencies of 32, 48, and 64 Hz that equate those used in a musical chord, hereby defined as musical vibroacupuncture (MVA), a single frequency of 32 Hz, set as vibroacupuncture (VA) and sham procedure (SP). CPT scores for pain thresholds and pain tolerance were assessed using repeated-measures ANOVAs. Pain intensity was evaluated using a numerical rating scale (NRS), while sensory and affective aspects of pain were rated using the short-form McGill Pain Questionnaire (SF-MPQ) and State-Trait Anxiety Inventory (STAI) Y-Form.ResultsPain thresholds did not vary significantly between trials. Pain tolerance scores were markedly higher in MVA compared to baseline (p = 0.0043) or SP (p = 0.006) but not for VA. Pain intensity for MVA also differed significantly from the baseline (p = 0.007) or SP (p = 0.027), but not for VA. No significant differences were found in SF-MPQ and STAI questionnaires.ConclusionsThese results suggest that MVA effectively increased pain tolerance and reduced pain intensity when compared with all groups, although not significant to the VA group.     

High-Definition Transcranial Infraslow Pink-Noise Stimulation Can Influence Functional and Effective Cortical Connectivity in Individuals With Chronic Low Back Pain: A Pilot Randomized Placebo-Controlled Study

IntroductionPain can be regarded as an emergent property of multiple interacting, dynamically changing brain networks and thus needs a targeted treatment approach. A novel high-definition transcranial infraslow pink-noise stimulation (HD-tIPNS) technique was developed to modulate the key hubs of the three main nociceptive pathways simultaneously, ie, the pregenual anterior cingulate cortex (pgACC) (descending inhibitory pathway), the dorsal anterior cingulate cortex (dACC) (medial nociceptive pathway), and both somatosensory cortices (S1) (lateral nociceptive pathway). This study aimed to evaluate safety and verify whether a single session of HD-tIPNS may disrupt functional and effective connectivity between targeted cortical regions.Materials and MethodsA pilot double-blind randomized two-arm placebo-controlled parallel trial was conducted. Participants (N = 30) with chronic low back pain were equally randomized to receive a single session of either sham stimulation or HD-tIPNS (targeting the pgACC, dACC, and bilateral S1). Primary outcomes included safety and electroencephalographic measures, and secondary outcomes included pain measures, collected after treatment. A Mann-Whitney U test was used to compare between-group differences in percentage changes with baseline for each outcome measures. A Wilcoxon signed-rank test was used to identify difference in effective connectivity measure before and after HD-tIPNS.ResultsNo serious adverse events were reported. A significant decrease in instantaneous functional connectivity was noted between the pgACC and dACC (U = 47.0, Z = −2.72, p = 0.007) and the pgACC and left S1 (U = 41.0, Z = −2.97, p = 0.003) in the infraslow band after HD-tIPNS when compared with sham stimulation. A significant decrease in instantaneous effective connectivity was noted in the direction of the dACC to the pgACC (Z = −2.10, p = 0.035), in the infraslow band after HD-tIPNS when compared with baseline. No changes in clinical pain measures were detected.ConclusionsHD-tIPNS can safely modulate the functional and effective connectivity between targeted pain-related cortical hubs. Further studies are warranted to evaluate whether repeated exposures to HD-tIPNS can incur clinical benefits through inducing changes in functional and effective connectivity at targeted cortical regions.Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is ACTRN12621001438842.     

Effectiveness of Repetitive Transcranial Magnetic Stimulation on Fibromyalgia Patients Responding to a First Repetitive Transcranial Magnetic Stimulation Induction Course After Six Months of Maintenance Treatment: A Randomized Pilot-Controlled Study

BackgroundFibromyalgia is a chronic painful condition without real, effective treatment. The administration of repetitive transcranial magnetic stimulation (rTMS) has been shown to have a therapeutic effect on pain, but there are still questions about the maintenance of its effect over time. Continuation of the treatment upon clinical response through maintenance sessions is promising and merits further exploration.Materials and MethodsWe conducted a randomized, parallel-group, controlled study involving 78 patients to evaluate the effect of rTMS vs sham stimulation after a three-week induction treatment and six months of maintenance treatment (three-week periodicity) on 22 patients who presented a clinical response to the induction treatment. The clinical response was defined as a ≥30% decrease of the baseline visual analog scale (VAS) for pain and a score for the Patient Global Impression of Change (PGIC) >5. The clinic global impression, fibromyalgia impact questionnaire, symptom severity score, and Beck’s depression inventory were also studied.ResultsA significant clinical response to treatment with rTMS was observed after the induction phase and maintained over six months, particularly as measured by the PGIC parameter of pain, as well as of the intensity of fatigue and depression, with an absence of adverse effects induced by this method.ConclusionA three-week rTMS treatment, characterized by a reduction in pain, as evaluated by VAS, should be continued with the administration of rTMS maintenance sessions for an additional six months to maintain the best possible long-term effects.     

1-Hz Repetitive Transcranial Magnetic Stimulation Increases Cerebral Vasomotor Reactivity: A Possible Autonomic Nervous System Modulation

BackgroundNeuromodulation techniques, i.e. repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), can modify cerebral hemodynamics. High frequency rTMS appeared to decrease cerebral vasomotor reactivity (VMR), while there is still poor evidence about the effect of low frequency (LF) rTMS on cerebral blood flow (CBF) and VMR.HypothesisThe present study aimed to test if LF rTMS decreases CBF and increases cerebral VMR. Monolateral or bilateral hemispheric involvement and duration of the effect were considered. A possible role of autonomic nervous system in CBF and VMR modulation was also investigated.MethodsTwenty-four right-handed healthy subjects underwent randomly real (12) or sham (12) 20-min 1-Hz rTMS on left primary motor cortex. Mean flow velocity and VMR of middle cerebral arteries were evaluated by means of transcranial Doppler before (T0), after 10 min (T1) and after 2 (T2), 5 (T3) and 24 h (T4) from rTMS. Heart rate variability (HRV) was studied within the same timing interval, assessing low frequency/high frequency (LF/HF) ratio as index of autonomic balance.ResultsAfter real rTMS compared with sham stimulation, MFV decreased bilaterally at T1 (F = 3.240, P = .030) while VMR increased bilaterally (F = 5.116, P = .002) for at least 5 h (T3). LF/HF ratio decreased early after real rTMS (F = 2.881, P = .040).Conclusion1-Hz rTMS may induce a bilateral long-lasting increase of VMR, while its effect on MFV is short-lasting. Moreover, HRV changes induced by rTMS suggest a possible autonomic nervous system modulation.     

Electrical Thalamic Stimulation in the Anterior Part of the Ventral Posterolateral Nucleus for the Treatment of Patients With Central Poststroke Pain

ObjectivesThe effects of thalamic stimulation of the anterior part of the ventral posterolateral nucleus (VPLa) for central poststroke pain (CPSP) and the pain-related electrophysiological characteristics of this structure were investigated.Materials and MethodsNine patients with CPSP manifesting as hemibody pain were enrolled. Stereotactic thalamic VPLa stimulation was implemented, and intraoperative electrophysiological studies on hyperactive and unstable discharges (HUDs) and responses to sensory and electrical stimulation were performed in the sensory thalamus. A preoperative somatosensory-evoked potential (SEP) study was carried out in all nine patients and in eight other patients with localized pain.ResultsThe patients were classified into two groups: a HUD-dominant group (group H, n = 5) and a sensory response-dominant group (group R, n = 4). HUDs were frequently encountered in the thalamic VPLa in the former group. The total number of HUDs and the number along the trajectory to the VPLa in group H were significantly larger than those in group R. The improvements on the pain numeric rating scale in group H were significantly higher than those in group R two years after surgery. The amplitude ratio of the SEP N20s in the ipsilateral to the contralateral side of CVD lesion in the study group was significantly lower than in the localized pain group.ConclusionsAdequate and stable pain relief with thalamic VPLa stimulation is obtainable in patients with CPSP who exhibit hyperactivity and electrical instability along the trajectory to this nucleus. Both responders and nonresponders were found to have severe dysfunction of the lemniscal system.     

The effect of transcranial direct stimulation as an add-on treatment to conventional physical therapy on pain intensity and functional ability in individuals with knee osteoarthritis: A randomized controlled trial

ObjectiveTo investigate the effect of adding transcranial direct current stimulation (tDCS) to conventional physiotherapy treatment (PT) on pain and performance of individuals with knee osteoarthritis (KOA).MethodsEighty people suffering from chronic KOA participated in this study. They were randomly divided into four treatment groups, including PT combined with tDCS over the primary motor cortex (M1), PT combined with tDCS over the primary sensory cortex (S1), PT combined with tDCS over the dorsolateral prefrontal cortex (DLPFC), and PT combined with sham tDCS. A visual analog scale (VAS) for pain intensity, the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire for knee-related disability, and several performance tests (stepping 15 s, chair stand test in 30 s, and walking 4 × 10 m) were used for assessment following 10 sessions of tDCS (T1), and one month after the last session of tDCS (T2).ResultsDifferential effects on pain intensity, knee-related disability, and performance were found between groups. Compared to sham tDCS: (i) tDCS over M1 improved VAS pain score, KOOS disability score, and performance tests at T1 and T2; (ii) tDCS over S1 improved VAS pain score at T1 and T2 and KOOS disability score and performance tests at T2; (iii) tDCS over the DLPFC improved VAS pain score at T1 and performance tests at T1 and T2.ConclusiontDCS could be a beneficial add-on treatment to conventional PT for pain relief, disability reduction and functional improvement in patients with KOA.     

Testing a Neurobiological Model of Depersonalization Disorder Using Repetitive Transcranial Magnetic Stimulation

BackgroundDepersonalization disorder (DPD) includes changes in subjective experiencing of self, encompassing emotional numbing. Functional magnetic resonance imaging (fMRI) has pointed to ventrolateral prefrontal cortex (VLPFC) inhibition of insula as a neurocognitive correlate of the disorder.ObjectiveWe hypothesized that inhibition to right VLPFC using repetitive transcranial magnetic stimulation (rTMS) would lead to increased arousal and reduced symptoms.MethodsPatients with medication-resistant DSM-IV DPD (N = 17) and controls (N = 20) were randomized to receive one session of right-sided rTMS to VLPFC or temporo-parietal junction (TPJ). 1Hz rTMS was guided using neuronavigation and delivered for 15 min. Co-primary outcomes were: (a) maximum skin conductance capacity, and (b) reduction in depersonalization symptoms (Cambridge Depersonalisation Scale (CDS) [state version]). Secondary outcomes included spontaneous fluctuations (SFs) and event-related skin conductance responses.ResultsIn patients with DPD, rTMS to VLPFC led to increased electrodermal capacity, namely maximum skin conductance deflections. Patients but not controls also showed increased SFs post rTMS. Patients who had either VLPFC or TPJ rTMS showed a similar significant reduction in symptoms. Event-related electrodermal activity did not change.ConclusionsA single session of right-sided rTMS to VLPFC (but not TPJ) significantly increased physiological arousal capacity supporting our model regarding the relevance of increased VLPFC activity to emotional numbing in DPD. rTMS to both sites led to reduced depersonalization scores but since this was independent of physiological arousal, this may be a non-specific effect. TMS is a potential therapeutic option for DPD; modulation of VLPFC, if replicated, is a plausible mechanism.     

Late-onset thermal hypersensitivity after focal ischemic thalamic infarcts as a model for central post-stroke pain in rats

Central post-stroke pain (CPSP) is a neuropathic pain syndrome that often develops in a delayed manner after thalamic stroke. Here, we describe a new model of CPSP by stereotaxic thalamic injection of endothelin-1. Stroke rats (n=12), but not saline-injected controls (n=12), developed a progressive, contralateral cutaneous thermal hyperalgesia over 4 weeks, without motor deficits. Lesions were highly focal and mainly affected the ventral posterior thalamic complex. Tchis model reproduces the infarct location and delayed hypersensitivity typical of CPSP, and may be useful to investigate its pathophysiology and test therapies targeting recovery and pain after thalamic stroke.     

Antidepressant Efficacy of High and Low Frequency rTMS at 110% of Motor Threshold versus Sham Stimulation over Left Prefrontal Cortex

BackgroundWhile the efficacy of repetitive transcranial magnetic stimulation (rTMS) at 10 Hz over the left prefrontal cortex has been repeatedly demonstrated, it is not clear that the optimal parameters for the treatment of depression have been adequately elucidated.ObjectivesWe sought to assess the antidepressant effectiveness of high and low frequency at a higher intensity rTMS compared to sham in patients with moderately treatment resistant depression.MethodThe authors conducted a three-week, double-blind, randomized, sham-controlled study of 24 acutely depressed patients given either active 20 Hz (n = 8) or 1 Hz (n = 8) rTMS (at 110% of motor threshold [MT]) or sham treatments (n = 8) over the left prefrontal cortex. Hamilton Depression ratings were analyzed by ANOVA.ResultsPatients on both frequencies showed greater improvement than on sham, which was associated with minor increases in depression. During open continuation to allow 7 weeks of active treatment in all individuals, additional improvement was observed.ConclusionsThe results seen here using 110% of MT for 3 weeks were more robust than those of previous studies of 1-Hz or 20-Hz rTMS for 2 weeks (at 80% and 100% of MT). The results also raise the possibility that both high and low frequency rTMS over left prefrontal cortex (and not just low frequency over the right prefrontal cortex) exert antidepressant effects, but further work is required to assess what parameters may be most effective in general and for a given individual.     

A Double-blind,Randomized Trial of Deep Repetitive Transcranial Magnetic Stimulation (rTMS) for Autism Spectrum Disorder

BackgroundBiomedical treatment options for autism spectrum disorder (ASD) are extremely limited. Repetitive transcranial magnetic stimulation (rTMS) is a safe and efficacious technique when targeting specific areas of cortical dysfunction in major depressive disorder, and a similar approach could yield therapeutic benefits in ASD, if applied to relevant cortical regions.ObjectiveThe aim of this study was to examine whether deep rTMS to bilateral dorsomedial prefrontal cortex improves social relating in ASD.Methods28 adults diagnosed with either autistic disorder (high-functioning) or Asperger's disorder completed a prospective, double-blind, randomized, placebo-controlled design with 2 weeks of daily weekday treatment. This involved deep rTMS to bilateral dorsomedial prefrontal cortex (5 Hz, 10-s train duration, 20-s inter-train interval) for 15 min (1500 pulses per session) using a HAUT-Coil. The sham rTMS coil was encased in the same helmet of the active deep rTMS coil, but no effective field was delivered into the brain. Assessments were conducted before, after, and one month following treatment.ResultsParticipants in the active condition showed a near significant reduction in self-reported social relating symptoms from pre-treatment to one month follow-up, and a significant reduction in social relating symptoms (relative to sham participants) for both post-treatment assessments. Those in the active condition also showed a reduction in self-oriented anxiety during difficult and emotional social situations from pre-treatment to one month follow-up. There were no changes for those in the sham condition.ConclusionDeep rTMS to bilateral dorsomedial prefrontal cortex yielded a reduction in social relating impairment and socially-related anxiety. Further research in this area should employ extended rTMS protocols that approximate those used in depression in an attempt to replicate and amplify the clinical response.     

Effects of high-frequency repetitive transcranial magnetic stimulation on reducing hemiplegic shoulder pain in patients with chronic stoke: a randomized controlled trial

Objective: To examine whether high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS), applied over the primary motor cortex of the affected hemisphere, could be used to manage hemiplegic shoulder pain (HSP).

Methods: Twenty-four chronic stroke patients with chronic HSP, randomly assigned into the rTMS group (10 sessions of high-frequency stimulation) or the sham group (sham stimulation), were performed. The Numeric Rating Scale (NRS) was used to evaluate the intensity of pain at pretreatment, and at 1 day, and 1, 2 and 4 weeks after treatment. Changes in upper-limb motor function were evaluated using the Motricity Index (MI-UL) and modified Brunnstrom Classification (MBC).

Results: When compared to pretreatment, the rTMS group showed a significant decrease in the NRS score at 1 day, and 1, 2 and 4 weeks after finishing rTMS sessions, with no significant change in the sham group. The NRS score after the rTMS sessions reduced by 30.1% at 1 day, 29.3% at 1 week, 28.0% at 2 weeks and 25.3% at 4 weeks. Passive shoulder range of motion, MI-UL, and MBC, however, did not significantly change in either group.

Conclusions: High-frequency rTMS could be used as a safe, beneficial therapeutic tool to manage HSP. We think it can be used as an adjuvant therapeutic modality to enhance the therapeutic outcome of HSP.     

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.