Effects of Transcutaneous Spinal Direct Current Stimulation (tsDCS) in Patients With Chronic Pain: A Clinical and Neurophysiological Study.

Background and Aims: Chronic pain is a complex clinical condition, often devastating for patients and unmanageable with pharmacological treatments. Converging evidence suggests that transcutaneous spinal Direct Current Stimulation (tsDCS) might represent a complementary therapy in managing chronic pain. In this randomized, double-blind and sham-controlled crossover study, we assessed tsDCS effects in chronic pain patients. Methods: Sixteen patients (aged 65.06 ± 16.16 years, eight women) with chronic pain of different etiology underwent sham and anodal tsDCS (anode over the tenth thoracic vertebra, cathode over the somatosensory cortical area: 2.5 mA, 20 min, 5 days for 1 week). As outcomes, we considered the Visual Analog Scale (VAS), the Neuropathic Pain Symptom Inventory (NPSI), and the components of the lower limb flexion reflex (LLFR), i.e., RIII threshold, RII latency and area, RIII latency and area, and flexion reflex (FR) total area. Assessments were conducted before (T0), immediately at the end of the treatment (T1), after 1 week (T2) and 1 month (T3). Results: Compared to sham, anodal tsDCS reduced RIII area at T2 (p = 0.0043) and T3 (p = 0.0012); similarly, FR total area was reduced at T3 (p = 0.03). Clinically, anodal tsDCS dampened VAS at T3 (p = 0.015), and NPSI scores at T1 (p = 0.0012), and T3 (p = 0.0015), whereas sham condition left them unchanged. Changes in VAS and NPSI scores linearly correlated with the reduction in LLFR areas (p = 0.0004). Conclusions: Our findings suggest that tsDCS could modulate nociceptive processing and pain perception in chronic pain syndromes.

Spinal direct current stimulation (tsDCS) in hereditary spastic paraplegias (HSP): A sham-controlled crossover study.

Objective: Hereditary spastic paraplegia (HSP) represents a heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and lower limb weakness. We assessed the effects of transcutaneous spinal direct current stimulation (tsDCS) in HSP.Design: A double-blind, randomized, crossover and sham-controlled study.Setting: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan.Participants: eleven patients with HSP (six men, mean age ± SD: 37.3 ± 8.1 years), eight affected by spastin/SPG4,1 by atlastin1/SPG3a, 1 by paraplegin/SPG7 and 1 by ZFYVE26/SPG15.Interventions: tsDCS (anodal or sham, 2.0 mA, 20', five days) delivered over the thoracic spinal cord (T10-T12).Outcome measures: Motor-evoked potentials (MEPs), the H-reflex (Hr), F-waves, the Ashworth scale for clinical spasticity, the Five Minutes Walking test and the Spastic Paraplegia Rating Scale (SPRS) were assessed. Patients were evaluated before tsDCS (T0), at the end of the stimulation (T1), after one week (T2), one month (T3) and two months (T4).Results: The score of the Ashworth scale improved in the anodal compared with sham group, up to two months following the end of stimulation (T1, P = .0137; T4, P = .0244), whereas the Five Minutes Walking test and SPRS did not differ between the two groups. Among neurophysiological measures, both anodal and sham tsDCS left Hr, F-waves and MEPs unchanged over time.Conclusions: Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.

High Hypnotizability Impairs the Cerebellar Control of Pain.

In the general population, transcranial anodal direct current stimulation of the cerebellum (ctDCS) reduces pain intensity and the amplitude of nociceptive laser evoked potentials (LEPs), whereas cathodal ctDCS elicits opposite effects. Since behavioral findings suggest that the cerebellar activity of highly hypnotizable individuals (highs) differs from the general population, we investigated whether hypnotizability-related differences occur in the modulation of pain by ctDCS. Sixteen healthy highs (according to the Stanford Hypnotic Susceptibility Scale, form A) and 16 participants not selected according to hypnotizability (controls) volunteered to undergo laser nociceptive stimulation of the dorsum of the left hand before and after anodal or cathodal ctDCS. LEPs amplitudes and latencies and the subjective pain experience (Numerical Rating Scale) were analyzed. Smaller LEP amplitudes and longer latencies were observed in highs with respect to controls independently of stimulation. After anodal and cathodal cerebellar stimulation, controls reported lower and higher pain than before it, respectively. In contrast, highs did not report significant changes in the perceived pain after both stimulations. They increased significantly their N2/P2 amplitude after anodal ctDCS and did not exhibit any significant change after cathodal tDCS, whereas controls decreased the N1 and N2P2 amplitude and increased their latency after anodal cerebellar stimulation and did the opposite after cathodal ctDCS. In conclusion, the study showed impaired cerebellar pain modulation and suggested altered cerebral cortical representation of pain in subjects with high hypnotizability scores.

An unexpected target of spinal direct current stimulation: Interhemispheric connectivity in humans.

BACKGROUND: Transcutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak electrical currents over spinal cord. NEW METHOD: We studied the effects of tsDCS on interhemispheric motor connectivity and visual processing by evaluating changes in ipsilateral Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual Evoked Potentials (hVEPs), before (T0) and at a different intervals following sham, anodal and cathodal tsDCS (T9-T11 level, 2.0 mA, 20'). Motor Evoked Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of a horizontal square wave grating with the display positioned in the right hemifield. RESULTS: Anodal tsDCS increased TCT (p < 0.001) and the interhemispheric delay for both the main VEP components (N1: p = 0.0003; P1: p < 0.0001), dampening at the same time iSP duration (APB: p < 0.0001; AH: p = 0.0005; deltoid: p < 0.0001), while cathodal stimulation elicited opposite effects (p < 0.0001). DISCUSSION: tsDCS modulates interhemispheric processing in a polarity-specific manner, with anodal stimulation leading to a functional disconnection between hemispheres. tsDCS would be a new promising therapeutic tool in managing a number of human diseases characterized by an impaired interhemispheric balance, or an early rehabilitation strategy in patients with acute brain lesions, when other non-invasive brain stimulation techniques (NIBS) are not indicated due to safety concerns.

Transcutaneous spinal direct current stimulation modulates human corticospinal system excitability.

This study aimed to assess the effects of thoracic anodal and cathodal transcutaneous spinal direct current stimulation (tsDCS) on upper and lower limb corticospinal excitability. Although there have been studies assessing how thoracic tsDCS influences the spinal ascending tract and reflexes, none has assessed the effects of this technique over upper and lower limb corticomotor neuronal connections. In 14 healthy subjects we recorded motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and hand abductor digiti minimi (ADM) muscles before (baseline) and at different time points (0 and 30 min) after anodal or cathodal tsDCS (2.5 mA, 20 min, T9-T11 level). In 8 of the 14 subjects we also tested the soleus H reflex and the F waves from AH and ADM before and after tsDCS. Both anodal and cathodal tsDCS left the upper limb MEPs and F wave unchanged. Conversely, while leaving lower limb H reflex unchanged, they oppositely affected lower limb MEPs: whereas anodal tsDCS increased resting motor threshold [(mean ± SE) 107.33 ± 3.3% increase immediately after tsDCS and 108.37 ± 3.2% increase 30 min after tsDCS compared with baseline] and had no effects on MEP area and latency, cathodal tsDCS increased MEP area (139.71 ± 12.9% increase immediately after tsDCS and 132.74 ± 22.0% increase 30 min after tsDCS compared with baseline) without affecting resting motor threshold and MEP latency. Our results show that tsDCS induces polarity-specific changes in corticospinal excitability that last for >30 min after tsDCS offset and selectively affect responses in lower limb muscles innervated by lumbar and sacral motor neurons.

Cathodal transcutaneous spinal direct current stimulation (tsDCS) improves motor unit recruitment in healthy subjects.

Transcutaneous spinal direct current stimulation (tsDCS) is a new promising technique for modulating spinal cord function in humans. However, its effects on corticospinal pathways and lower motorneuron excitability are poorly understood. We studied the effects of tsDCS on motor unit recruitment by evaluating changes in motor unit number (MUNE) and peripheral silent period (PSP) after sham (s-tsDCS), anodal (a-tsDCS) and cathodal (c-tsDCS) tsDCS applied either over the cervical or the lower thoracic spinal cord in healthy subjects. For the calculation of MUNE we used the multipoint incremental technique recording from either the ulnar nerve innervated abductor digiti minimi (ADM) or the median nerve innervated abductor pollicis brevis (APB) muscle. c-tsDCS dramatically increases MUNE values following cervical polarization, while sham and anodal polarization have no significant effect (APB: F(4,99)=26.4, p<0.001, two-way repeated measures ANOVA with "time" and "stimulation" as factors; ADM: F(4,99)=22.1, p<0.0001). At the same time, c-tsDCS dampened PSP respect to sham and anodal conditions (p<0.0001). Interestingly, also thoracic c-tsDCS significantly improved motor unit recruitment compared with both s-tsDCS and a-tsDCS (APB: F(4,99)=20.1, p<0.0001; ADM: F(4,99)=16.6, p<0.0001). Our data in healthy subjects suggest that tsDCS, possibly also through supraspinal effects, could provide a novel therapeutic tool in managing several pathological conditions characterized by reduced motor unit recruitment, such as stroke and spinal cord injuries.

Transcranial direct current stimulation (tDCS) for fatigue in multiple sclerosis.

BACKGROUND: The debilitating fatigue that patients with multiple sclerosis (MS) commonly experience during day-to-day living activities responds poorly to current therapeutic options. Direct currents (DC) delivered through the scalp (transcranial DC stimulation or tDCS) at weak intensities induce changes in motor cortical excitability that persist for almost an hour after current offset and depend on current polarity. tDCS successfully modulates cortical excitability in various clinical disorders but no information is available for MS related fatigue. OBJECTIVE: In this study we aimed to assess fatigue symptom after five consecutive sessions of anodal tDCS applied over the motor cortex in patients with MS. METHODS: We enrolled 25 patients with MS all of whom experienced fatigue. We delivered anodal and sham tDCS in random order in two separate experimental sessions at least 1 month apart. The stimulating current was delivered for 15 minutes once a day for 5 consecutive days. In each session the Fatigue Impact Scale (FIS) and the Back Depression Inventory (BDI) were administered before the treatment (baseline), immediately after treatment on day five (T1), one week (T2) and three weeks (T3) after the last tDCS session. RESULTS: All patients tolerated tDCS well without adverse events. The fatigue score significantly decreased after anodal tDCS in 65% of the patients (responders). After patients received tDCS for 5 days their FIS scores improved by about 30% and the tDCS-induced benefits persisted at T2 and T3. CONCLUSION: Our preliminary findings suggest that anodal tDCS applied over the motor cortex, could improve fatigue in most patients with MS.