Advertisement

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

  • Mauricio F. Villamar
    Affiliations
    Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

    School of Medicine, Pontifical Catholic University of Ecuador, Quito, Ecuador
    Search for articles by this author
  • Pakorn Wivatvongvana
    Affiliations
    Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

    Department of Rehabilitation Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
    Search for articles by this author
  • Jayanton Patumanond
    Affiliations
    Clinical Epidemiology & Clinical Statistics Unit, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
    Search for articles by this author
  • Marom Bikson
    Affiliations
    Department of Biomedical Engineering, The City College of New York of CUNY, New York, New York
    Search for articles by this author
  • Dennis Q. Truong
    Affiliations
    Department of Biomedical Engineering, The City College of New York of CUNY, New York, New York
    Search for articles by this author
  • Abhishek Datta
    Affiliations
    Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

    Department of Biomedical Engineering, The City College of New York of CUNY, New York, New York
    Search for articles by this author
  • Felipe Fregni
    Correspondence
    Address reprint requests to Felipe Fregni, MD, PhD, MPH, Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, 125 Nashua St #726, Boston, MA 02114.
    Affiliations
    Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
    Search for articles by this author
Published:February 18, 2013DOI:https://doi.org/10.1016/j.jpain.2012.12.007

      Abstract

      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.

      Perspective

      4×1-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.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Andre-Obadia N.
        • Peyron R.
        • Mertens P.
        • Mauguiere F.
        • Laurent B.
        • Garcia-Larrea L.
        Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy.
        Clin Neurophysiol. 2006; 117: 1536-1544
        • Antal A.
        • Brepohl N.
        • Poreisz C.
        • Boros K.
        • Csifcsak G.
        • Paulus W.
        Transcranial direct current stimulation over somatosensory cortex decreases experimentally induced acute pain perception.
        Clin J Pain. 2008; 24: 56-63
        • Antal A.
        • Paulus W.
        A case of refractory orofacial pain treated by transcranial direct current stimulation applied over hand motor area in combination with NMDA agonist drug intake.
        Brain Stimul. 2011; 4: 117-121
        • Antal A.
        • Terney D.
        • Kuhnl S.
        • Paulus W.
        Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition.
        J Pain Symptom Manage. 2010; 39: 890-903
        • Bachmann C.G.
        • Muschinsky S.
        • Nitsche M.A.
        • Rolke R.
        • Magerl W.
        • Treede R.D.
        • Paulus W.
        • Happe S.
        Transcranial direct current stimulation of the motor cortex induces distinct changes in thermal and mechanical sensory percepts.
        Clinical Neurophysiol. 2010; 121: 2083-2089
        • Bannwarth B.
        • Blotman F.
        • Roue-Le Lay K.
        • Caubere J.P.
        • Andre E.
        • Taieb C.
        Fibromyalgia syndrome in the general population of France: A prevalence study.
        Joint Bone Spine. 2009; 76: 184-187
        • Beck A.T.
        • Steer R.A.
        • Brown G.K.
        Manual for Beck Depression Inventory II (BDI-II).
        Psychology Corporation, San Antonio, TX1996
        • Boggio P.S.
        • Zaghi S.
        • Lopes M.
        • Fregni F.
        Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers.
        Eur J Neurol. 2008; 15: 1124-1130
        • Borckardt J.J.
        • Bikson M.
        • Frohman H.
        • Reeves S.T.
        • Datta A.
        • Bansal V.
        • Madan A.
        • Barth K.
        • George M.S.
        A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception.
        J Pain. 2012; 13: 112-120
        • Burckhardt C.S.
        • Woods S.L.
        • Schultz A.A.
        • Ziebarth D.M.
        Quality of life of adults with chronic illness: A psychometric study.
        Res Nurs Health. 1989; 12: 347-354
        • Dasilva A.F.
        • Mendonca M.E.
        • Zaghi S.
        • Lopes M.
        • Dossantos M.F.
        • Spierings E.L.
        • Bajwa Z.
        • Datta A.
        • Bikson M.
        • Fregni F.
        tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine.
        Headache. 2012; 52: 1283-1295
        • Datta A.
        • Bansal V.
        • Diaz J.
        • Patel J.
        • Reato D.
        • Bikson M.
        Gyri-precise head model of transcranial DC stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad.
        Brain Stimul. 2009; 2: 201-207
        • Diers M.
        • Koeppe C.
        • Yilmaz P.
        • Thieme K.
        • Markela-Lerenc J.
        • Schiltenwolf M.
        • van Ackern K.
        • Flor H.
        Pain ratings and somatosensory evoked responses to repetitive intramuscular and intracutaneous stimulation in fibromyalgia syndrome.
        J Clin Neurophysiol. 2008; 25: 153-160
        • Dmochowski J.P.
        • Datta A.
        • Bikson M.
        • Su Y.
        • Parra L.C.
        Optimized multi-electrode stimulation increases focality and intensity at target.
        J Neural Eng. 2011; 8: 046011
        • Fenton B.W.
        • Palmieri P.A.
        • Boggio P.
        • Fanning J.
        • Fregni F.
        A preliminary study of transcranial direct current stimulation for the treatment of refractory chronic pelvic pain.
        Brain Stimul. 2009; 2: 103-107
        • Fregni F.
        • Freedman S.
        • Pascual-Leone A.
        Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques.
        Lancet Neurol. 2007; 6: 188-191
        • Fregni F.
        • Gimenes R.
        • Valle A.C.
        • Ferreira M.J.
        • Rocha R.R.
        • Natalle L.
        • Bravo R.
        • Rigonatti S.P.
        • Freedman S.D.
        • Nitsche M.A.
        • Pascual-Leone A.
        • Boggio P.S.
        A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia.
        Arthritis Rheum. 2006; 54: 3988-3998
        • Fricke K.
        • Seeber A.A.
        • Thirugnanasambandam N.
        • Paulus W.
        • Nitsche M.A.
        • Rothwell J.C.
        Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex.
        J Neurophysiol. 2011; 105: 1141-1149
        • Gandiga P.C.
        • Hummel F.C.
        • Cohen L.G.
        Transcranial DC stimulation (tDCS): A tool for double-blind sham-controlled clinical studies in brain stimulation.
        Clin Neurophysiol. 2006; 117: 845-850
        • Hahn C.
        • Rice J.
        • Macuff S.
        • Minhas P.
        • Rahman A.
        • Bikson M.
        Methods for extra-low voltage transcranial direct current stimulation: Current and time dependent impedance decreases.
        Clin Neurophysiol. 2012 Sep 29; ([Epub ahead of print])
        • Harris R.E.
        • Williams D.A.
        • McLean S.A.
        • Sen A.
        • Hufford M.
        • Gendreau R.M.
        • Gracely R.H.
        • Clauw D.J.
        Characterization and consequences of pain variability in individuals with fibromyalgia.
        Arthritis Rheum. 2005; 52: 3670-3674
        • Henry D.E.
        • Chiodo A.E.
        • Yang W.
        Central nervous system reorganization in a variety of chronic pain states: A review.
        PM R. 2011; 3: 1116-1125
        • Jacobson L.
        • Koslowsky M.
        • Lavidor M.
        tDCS polarity effects in motor and cognitive domains: A meta-analytical review.
        Exp Brain Res. 2012; 216: 1-10
        • Knotkova H.
        • Homel P.
        • Cruciani R.A.
        Cathodal tDCS over the somatosensory cortex relieved chronic neuropathic pain in a patient with complex regional pain syndrome (CRPS/RSD).
        J Pain Manag. 2009; 2: 365-368
        • Kuo H.I.
        • Bikson M.
        • Datta A.
        • Minhas P.
        • Paulus W.
        • Kuo M.F.
        • Nitsche M.A.
        Comparing cortical plasticity induced by conventional and high-definition 4 x 1 ring tDCS: A neurophysiological study.
        Brain Stimul. 2012 Oct 13; ([Epub ahead of print])
        • Lang N.
        • Siebner H.R.
        • Ward N.S.
        • Lee L.
        • Nitsche M.A.
        • Paulus W.
        • Rothwell J.C.
        • Lemon R.N.
        • Frackowiak R.S.
        How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?.
        Eur J Neurosci. 2005; 22: 495-504
        • Lima M.C.
        • Fregni F.
        Motor cortex stimulation for chronic pain: Systematic review and meta-analysis of the literature.
        Neurology. 2008; 70: 2329-2337
        • Meeus M.
        • Nijs J.
        Central sensitization: A biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome.
        Clin Rheumatol. 2007; 26: 465-473
        • Merrill D.R.
        • Bikson M.
        • Jefferys J.G.
        Electrical stimulation of excitable tissue: Design of efficacious and safe protocols.
        J Neurosci Methods. 2005; 141: 171-198
        • Mhalla A.
        • Baudic S.
        • Ciampi de Andrade D.
        • Gautron M.
        • Perrot S.
        • Teixeira M.J.
        • Attal N.
        • Bouhassira D.
        Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia.
        Pain. 2011; 152: 1478-1485
        • Minhas P.
        • Bansal V.
        • Patel J.
        • Ho J.S.
        • Diaz J.
        • Datta A.
        • Bikson M.
        Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS.
        J Neurosci Methods. 2010; 190: 188-197
        • Neumann L.
        • Buskila D.
        Epidemiology of fibromyalgia.
        Curr Pain Headache Rep. 2003; 7: 362-368
        • Nitsche M.A.
        • Cohen L.G.
        • Wassermann E.M.
        • Priori A.
        • Lang N.
        • Antal A.
        • Paulus W.
        • Hummel F.
        • Boggio P.S.
        • Fregni F.
        • Pascual-Leone A.
        Transcranial direct current stimulation: State of the art 2008.
        Brain Stimul. 2008; 1: 206-223
        • Nitsche M.A.
        • Liebetanz D.
        • Schlitterlau A.
        • Henschke U.
        • Fricke K.
        • Frommann K.
        • Lang N.
        • Henning S.
        • Paulus W.
        • Tergau F.
        GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans.
        Eur J Neurosci. 2004; 19: 2720-2726
        • Nitsche M.A.
        • Paulus W.
        Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.
        J Physiol. 2000; 527: 633-639
        • Nitsche M.A.
        • Paulus W.
        Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans.
        Neurology. 2001; 57: 1899-1901
        • O’Connell N.E.
        • Wand B.M.
        • Marston L.
        • Spencer S.
        • Desouza L.H.
        Non-invasive brain stimulation techniques for chronic pain.
        Cochrane database of systematic reviews. 2010; : CD008208
        • Passard A.
        • Attal N.
        • Benadhira R.
        • Brasseur L.
        • Saba G.
        • Sichere P.
        • Perrot S.
        • Januel D.
        • Bouhassira D.
        Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia.
        Brain. 2007; 130: 2661-2670
        • Petzke F.
        • Khine A.
        • Williams D.
        • Groner K.
        • Clauw D.J.
        • Gracely R.H.
        Dolorimetry performed at 3 paired tender points highly predicts overall tenderness.
        J Rheumatol. 2001; 28: 2568-2569
        • Polania R.
        • Paulus W.
        • Nitsche M.A.
        Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation.
        Hum Brain Mapp. 2012; 33: 2499-2508
        • Reidler J.S.
        • Mendonca M.E.
        • Santana M.B.
        • Wang X.
        • Lenkinski R.
        • Motta A.F.
        • Marchand S.
        • Latif L.
        • Fregni F.
        Effects of motor cortex modulation and descending inhibitory systems on pain thresholds in healthy subjects.
        J Pain. 2012; 13: 450-458
        • Reilly E.L.
        EEG recording and operation of the apparatus.
        in: Niedermeyer E. Lopes da Silva F.H. Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. Lippincott Williams & Wilkins, Philadelphia, PA2004: 139-141
        • Riberto M.
        • Marcon Alfieri F.
        • Monteiro de Benedetto Pacheco K.
        • Dini Leite V.
        • Nemoto Kaihami H.
        • Fregni F.
        • Rizzo Battistella L.
        Efficacy of transcranial direct current stimulation coupled with a multidisciplinary rehabilitation program for the treatment of fibromyalgia.
        Open Rheumatol J. 2011; 5: 45-50
        • Roizenblatt S.
        • Fregni F.
        • Gimenez R.
        • Wetzel T.
        • Rigonatti S.P.
        • Tufik S.
        • Boggio P.S.
        • Valle A.C.
        Site-specific effects of transcranial direct current stimulation on sleep and pain in fibromyalgia: A randomized, sham-controlled study.
        Pain Pract. 2007; 7: 297-306
        • Sadleir R.J.
        • Vannorsdall T.D.
        • Schretlen D.J.
        • Gordon B.
        Transcranial direct current stimulation (tDCS) in a realistic head model.
        Neuroimage. 2010; 51: 1310-1318
        • Schulz K.F.
        • Altman D.G.
        • Moher D.
        • Fergusson D.
        CONSORT 2010 changes and testing blindness in RCTs.
        Lancet. 2010; 375: 1144-1146
        • Short E.B.
        • Borckardt J.J.
        • Anderson B.S.
        • Frohman H.
        • Beam W.
        • Reeves S.T.
        • George M.S.
        Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: A randomized, controlled pilot study.
        Pain. 2011; 152: 2477-2484
        • Tastekin N.
        • Uzunca K.
        • Sut N.
        • Birtane M.
        • Mercimek O.B.
        Discriminative value of tender points in fibromyalgia syndrome.
        Pain Med. 2010; 11: 466-471
      1. Truong DQ, Datta A, Xu J, Fregni F, Bikson M: Prefrontal Cortex transcranial direct current stimulation via a combined high definition and conventional electrode montage: A FEM modeling studying. Conference proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 2012:6608-6611, 2012

      2. Truong DQ, Magerowski G, Pascual-Leone A, Alonso-Alonso M, Bikson M: Finite Element Study of skin and fat delineation in an obese subject for transcranial direct current stimulation. Conference proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 2012:6587-6590, 2012

        • Valle A.
        • Roizenblatt S.
        • Botte S.
        • Zaghi S.
        • Riberto M.
        • Tufik S.
        • Boggio P.S.
        • Fregni F.
        Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: Results of a randomized, sham-controlled longitudinal clinical trial.
        J Pain Manag. 2009; 2: 353-361
        • Villamar M.F.
        • Contreras V.S.
        • Kuntz R.E.
        • Fregni F.
        The reporting of blinding in physical medicine and rehabilitation randomized controlled trials: A systematic review.
        J Rehabil Med. 2013; 45: 6-13
        • Villamar M.F.
        • Santos Portilla A.
        • Fregni F.
        • Zafonte R.
        Noninvasive brain stimulation to modulate neuroplasticity in traumatic brain injury.
        Neuromodulation. 2012; 15: 326-338
        • Wolfe F.
        • Clauw D.J.
        • Fitzcharles M.A.
        • Goldenberg D.L.
        • Katz R.S.
        • Mease P.
        • Russell A.S.
        • Russell I.J.
        • Winfield J.B.
        • Yunus M.B.
        The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.
        Arthritis Care Res (Hoboken). 2010; 62: 600-610
        • Wolfe F.
        • Ross K.
        • Anderson J.
        • Russell I.J.
        • Hebert L.
        The prevalence and characteristics of fibromyalgia in the general population.
        Arthritis Rheum. 1995; 38: 19-28
        • Woolf C.J.
        Central sensitization: Implications for the diagnosis and treatment of pain.
        Pain. 2011; 152: S2-15