The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment

Background: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clini...

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Main Authors: Eliana Berra, Roberto Bergamaschi, Roberto De Icco, Carlotta Dagna, Armando Perrotta, Marco Rovaris, Maria Grazia Grasso, Maria G. Anastasio, Giovanna Pinardi, Federico Martello, Stefano Tamburin, Giorgio Sandrini, Cristina Tassorelli
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-02-01
Series:Frontiers in Human Neuroscience
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Online Access:https://www.frontiersin.org/article/10.3389/fnhum.2019.00031/full
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author Eliana Berra
Roberto Bergamaschi
Roberto Bergamaschi
Roberto De Icco
Roberto De Icco
Carlotta Dagna
Armando Perrotta
Marco Rovaris
Maria Grazia Grasso
Maria G. Anastasio
Giovanna Pinardi
Federico Martello
Stefano Tamburin
Giorgio Sandrini
Giorgio Sandrini
Cristina Tassorelli
Cristina Tassorelli
spellingShingle Eliana Berra
Roberto Bergamaschi
Roberto Bergamaschi
Roberto De Icco
Roberto De Icco
Carlotta Dagna
Armando Perrotta
Marco Rovaris
Maria Grazia Grasso
Maria G. Anastasio
Giovanna Pinardi
Federico Martello
Stefano Tamburin
Giorgio Sandrini
Giorgio Sandrini
Cristina Tassorelli
Cristina Tassorelli
The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment
Frontiers in Human Neuroscience
neuropathic pain
transcutaneous spinal direct current stimulation (ts-DCS)
non-invasive
nociceptive withdrawal reflex
neuromodulation
multiple sclerosis
author_facet Eliana Berra
Roberto Bergamaschi
Roberto Bergamaschi
Roberto De Icco
Roberto De Icco
Carlotta Dagna
Armando Perrotta
Marco Rovaris
Maria Grazia Grasso
Maria G. Anastasio
Giovanna Pinardi
Federico Martello
Stefano Tamburin
Giorgio Sandrini
Giorgio Sandrini
Cristina Tassorelli
Cristina Tassorelli
author_sort Eliana Berra
title The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment
title_short The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment
title_full The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment
title_fullStr The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment
title_full_unstemmed The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment
title_sort effects of transcutaneous spinal direct current stimulation on neuropathic pain in multiple sclerosis: clinical and neurophysiological assessment
publisher Frontiers Media S.A.
series Frontiers in Human Neuroscience
issn 1662-5161
publishDate 2019-02-01
description Background: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients.Methods: Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group (n = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group (n = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS (n = 12) and sham ts-DCS (n = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level.Results: Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline.Conclusions: Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception.Clinical Trial Registration:www.ClinicalTrials.gov, identifier #NCT02331654.
topic neuropathic pain
transcutaneous spinal direct current stimulation (ts-DCS)
non-invasive
nociceptive withdrawal reflex
neuromodulation
multiple sclerosis
url https://www.frontiersin.org/article/10.3389/fnhum.2019.00031/full
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spelling doaj-2d1c8a8482284743ac5758fc3e5fbed12020-11-25T02:49:27ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612019-02-011310.3389/fnhum.2019.00031421502The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological AssessmentEliana Berra0Roberto Bergamaschi1Roberto Bergamaschi2Roberto De Icco3Roberto De Icco4Carlotta Dagna5Armando Perrotta6Marco Rovaris7Maria Grazia Grasso8Maria G. Anastasio9Giovanna Pinardi10Federico Martello11Stefano Tamburin12Giorgio Sandrini13Giorgio Sandrini14Cristina Tassorelli15Cristina Tassorelli16Neurorehabilitation Unit, Department of Neurology, IRCCS C. Mondino Foundation, Pavia, ItalyNeurorehabilitation Unit, Department of Neurology, IRCCS C. Mondino Foundation, Pavia, ItalyMultiple Sclerosis Center, IRCCS C. Mondino Foundation, Pavia, ItalyNeurorehabilitation Unit, Department of Neurology, IRCCS C. Mondino Foundation, Pavia, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyDepartment of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, ItalyIRCCS Neuromed, Pozzilli, ItalyNeurorehabilitation Unit and Multiple Sclerosis Center, IRCCS Santa Maria Nascente, Don Carlo Gnocchi Foundation, Milan, ItalyMultiple Sclerosis Unit, Rehabilitation Hospital Santa Lucia Foundation, Rome, ItalyIRCCS Neuromed, Pozzilli, ItalyNeurorehabilitation Unit and Multiple Sclerosis Center, IRCCS Santa Maria Nascente, Don Carlo Gnocchi Foundation, Milan, ItalyMultiple Sclerosis Unit, Rehabilitation Hospital Santa Lucia Foundation, Rome, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, ItalyNeurorehabilitation Unit, Department of Neurology, IRCCS C. Mondino Foundation, Pavia, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyNeurorehabilitation Unit, Department of Neurology, IRCCS C. Mondino Foundation, Pavia, ItalyDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalyBackground: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients.Methods: Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group (n = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group (n = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS (n = 12) and sham ts-DCS (n = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level.Results: Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline.Conclusions: Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception.Clinical Trial Registration:www.ClinicalTrials.gov, identifier #NCT02331654.https://www.frontiersin.org/article/10.3389/fnhum.2019.00031/fullneuropathic paintranscutaneous spinal direct current stimulation (ts-DCS)non-invasivenociceptive withdrawal reflexneuromodulationmultiple sclerosis