Abstract
Fibromyalgia is a disorder characterized by widespread musculoskeletal pain frequently accompanied by other symptoms such as fatigue. Moderate improvement from pharmacological and non-pharmacological treatments have proposed non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) to the occipital nerve (more specifically the C2 area) or to the dorsolateral prefrontal cortex (DLPFC) as potential treatments. We aimed to explore the effectiveness of repeated sessions of tDCS (eight sessions) targeting the C2 area and DLPFC in reducing fibromyalgia symptoms, more specifically pain and fatigue. Forty-two fibromyalgia patients received either C2 tDCS, DLPFC tDCS or sham procedure (15 C2 tDCS–11 DLPFC tDCS–16 sham). All groups were treated with eight sessions (two times a week for 4 weeks). Our results show that repeated sessions of C2 tDCS significantly improved pain, but not fatigue, in fibromyalgia patients, whereas repeated sessions of DLPFC tDCS significantly improved pain as well as fatigue. This study shows that eight sessions of tDCS targeting the DLPFC have a more general relief in fibromyalgia patients than when targeting the C2 area, suggesting that stimulating different targets with eight sessions of tDCS can lead to benefits on different symptom dimensions of fibromyalgia.
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References
Arnold LM (2008) Management of fibromyalgia and comorbid psychiatric disorders. J Clin Psychiatry 69(Suppl 2):14–19
Ayache SS, Palm U, Chalah MA et al (2016) Prefrontal tDCS decreases pain in patients with multiple sclerosis. Front Neurosci 10:147. doi:10.3389/fnins.2016.00147
Baliki MN, Geha PY, Apkarian AV, Chialvo DR (2008) Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics. J Neurosci 28:1398–1403. doi:10.1523/JNEUROSCI.4123-07.2008
Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L (2007) An internet survey of 2,596 people with fibromyalgia. BMC Musculoskelet Disord 8:27. doi:10.1186/1471-2474-8-27
Bester M, Lazar M, Petracca M, Babb JS, Herbert J, Grossman RI, Inglese M (2013) Tract-specific white matter correlates of fatigue and cognitive impairment in benign multiple sclerosis. J Neurol Sci 330:61–66. doi:10.1016/j.jns.2013.04.005
Boggio PS, Ferrucci R, Rigonatti SP, Covre P, Nitsche M, Pascual-Leone A, Fregni F (2006) Effects of transcranial direct current stimulation on working memory in patients with Parkinson’s disease. J Neurol Sci 249:31–38. doi:10.1016/j.jns.2006.05.062
Boggio PS, Zaghi S, Lopes M, Fregni F (2008) Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers. Eur J Neurol 15:1124–1130. doi:10.1111/j.1468-1331.2008.02270.x
Boissoneault J, Letzen J, Lai S, O’Shea A, Craggs J, Robinson ME, Staud R (2016) Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study. Magn Reson Imaging 34:603–608. doi:10.1016/j.mri.2015.12.008
Borckardt JJ, Weinstein M, Reeves ST et al (2006) Postoperative left prefrontal repetitive transcranial magnetic stimulation reduces patient-controlled analgesia use. Anesthesiology 105:557–562
Borckardt JJ, Smith AR, Reeves ST et al (2007) Fifteen minutes of left prefrontal repetitive transcranial magnetic stimulation acutely increases thermal pain thresholds in healthy adults. Pain Res Manag 12:287–290
Borckardt JJ, Smith AR, Reeves ST et al (2009) A pilot study investigating the effects of fast left prefrontal rTMS on chronic neuropathic pain. Pain Med 10:840–849. doi:10.1111/j.1526-4637.2009.00657.x
Borckardt JJ, Romagnuolo J, Reeves ST, Madan A, Frohman H, Beam W, George MS (2011) Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study. Gastrointest Endosc 73:1158–1164. doi:10.1016/j.gie.2011.01.050
Brighina F, De Tommaso M, Giglia F et al (2011) Modulation of pain perception by transcranial magnetic stimulation of left prefrontal cortex. J Headache Pain 12:185–191. doi:10.1007/s10194-011-0322-8
Brunelin J, Mondino M, Gassab L et al (2012) Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry 169:719–724. doi:10.1176/appi.ajp.2012.11071091
Castillo-Saavedra L, Gebodh N, Bikson M et al (2016) Clinically effective treatment of fibromyalgia pain with high-definition transcranial direct current stimulation: phase II open-label dose optimization. J Pain 17:14–26. doi:10.1016/j.jpain.2015.09.009
Chadaide Z, Arlt S, Antal A, Nitsche MA, Lang N, Paulus W (2007) Transcranial direct current stimulation reveals inhibitory deficiency in migraine. Cephalalgia 27:833–839. doi:10.1111/j.1468-2982.2007.01337.x
Chinn S, Caldwell W, Gritsenko K (2016) Fibromyalgia pathogenesis and treatment options update. Curr Pain Headache Rep 20:25. doi:10.1007/s11916-016-0556-x
Cook DB, O’Connor PJ, Lange G, Steffener J (2007a) Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. Neuroimage 36:108–122. doi:10.1016/j.neuroimage.2007.02.033
Cook DB, Stegner AJ, McLoughlin MJ (2007b) Imaging pain of fibromyalgia. Curr Pain Headache Rep 11:190–200
Cummiford CM, Nascimento TD, Foerster BR, Clauw DJ, Zubieta JK, Harris RE, DaSilva AF (2016) Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients. Arthritis Res Ther 18:40. doi:10.1186/s13075-016-0934-0
DallAgnol L, Pascoal-Faria P, Barros Cecilio S, Correa FI (2015) Transcranial direct current stimulation in the neuromodulation of pain in fibromyalgia: a case study. Ann Phys Rehabil Med 58:351–353. doi:10.1016/j.rehab.2015.10.002
Dehghan M, Schmidt-Wilcke T, Pfleiderer B et al (2016) Coordinate-based (ALE) meta-analysis of brain activation in patients with fibromyalgia. Hum Brain Mapp 37:1749–1758. doi:10.1002/hbm.23132
DeLuca J, Genova HM, Hillary FG, Wylie G (2008) Neural correlates of cognitive fatigue in multiple sclerosis using functional MRI. J Neurol Sci 270:28–39. doi:10.1016/j.jns.2008.01.018
Diers M, Koeppe C, Yilmaz P et al (2008) Pain ratings and somatosensory evoked responses to repetitive intramuscular and intracutaneous stimulation in fibromyalgia syndrome. J Clin Neurophysiol 25:153–160. doi:10.1097/WNP.0b013e31817759c5
Fagerlund AJ, Hansen OA, Aslaksen PM (2015) Transcranial direct current stimulation as a treatment for patients with fibromyalgia: a randomized controlled trial. Pain 156:62–71. doi:10.1016/j.pain.0000000000000006
Filippi M, Rocca MA, Colombo B, Falini A, Codella M, Scotti G, Comi G (2002) Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. Neuroimage 15:559–567. doi:10.1006/nimg.2001.1011
Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF (1994) Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis 18(Suppl 1):S79–S83
Foerster BR, Nascimento TD, DeBoer M et al (2015) Excitatory and inhibitory brain metabolites as targets of motor cortex transcranial direct current stimulation therapy and predictors of its efficacy in fibromyalgia. Arthritis Rheumatol 67:576–581. doi:10.1002/art.38945
Fregni F, Boggio PS, Nitsche MA, Marcolin MA, Rigonatti SP, Pascual-Leone A (2006a) Treatment of major depression with transcranial direct current stimulation. Bipolar Disord 8:203–204. doi:10.1111/j.1399-5618.2006.00291.x
Fregni F, Gimenes R, Valle AC et al (2006b) A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum 54:3988–3998. doi:10.1002/art.22195
Fregni F et al (2006c) A Randomized, Sham-Controlled, Proof of Principle Study of Transcranial Direct Current Stimulation for the Treatment of Pain in Fibromyalgia. Arthritis Rheum 54:3988–3998
Fregni F, Liguori P, Fecteau S, Nitsche MA, Pascual-Leone A, Boggio PS (2008) Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study. J Clin Psychiatry 69:32–40
Garcia-Larrea L, Peyron R (2013) Pain matrices and neuropathic pain matrices: a review. Pain 154(Suppl 1):S29–S43. doi:10.1016/j.pain.2013.09.001
Gay CW, Robinson ME, Lai S, O’Shea A, Craggs JG, Price DD, Staud R (2016) Abnormal resting-state functional connectivity in patients with chronic fatigue syndrome: results of seed and data-driven analyses. Brain Connect 6:48–56. doi:10.1089/brain.2015.0366
Ghavidel-Parsa B, Bidari A, Amir Maafi A, Ghalebaghi B (2015) The Iceberg nature of fibromyalgia burden: the clinical and economic aspects. Korean J Pain 28:169–176. doi:10.3344/kjp.2015.28.3.169
Graff-Guerrero A, Gonzalez-Olvera J, Fresan A, Gomez-Martin D, Mendez-Nunez JC, Pellicer F (2005) Repetitive transcranial magnetic stimulation of dorsolateral prefrontal cortex increases tolerance to human experimental pain. Brain Res Cogn Brain Res 25:153–160. doi:10.1016/j.cogbrainres.2005.05.002
Jensen KB, Srinivasan P, Spaeth R et al (2013) Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain. Arthritis Rheum 65:3293–3303. doi:10.1002/art.38170
Jones GT, Atzeni F, Beasley M, Fluss E, Sarzi-Puttini P, Macfarlane GJ (2015) The prevalence of fibromyalgia in the general population: a comparison of the American College of Rheumatology 1990, 2010, and modified 2010 classification criteria. Arthritis Rheumatol 67:568–575. doi:10.1002/art.38905
Kovacs S, Peeters R, De Ridder D, Plazier M, Menovsky T, Sunaert S (2011) Central effects of occipital nerve electrical stimulation studied by functional magnetic resonance imaging. Neuromodulation 14:46–55. doi:10.1111/j.1525-1403.2010.00312.x (discussion 56–47)
Lefaucheur JP, Andre-Obadia N, Antal A et al (2014) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 125:2150–2206. doi:10.1016/j.clinph.2014.05.021
Lefaucheur JP, Antal A, Ayache SS et al (2017) Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. doi:10.1016/j.clinph.2016.10.087
Lorenz J, Cross DJ, Minoshima S, Morrow TJ, Paulson PE, Casey KL (2002) A unique representation of heat allodynia in the human brain. Neuron 35:383–393
Lorenz J, Minoshima S, Casey KL (2003) Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation. Brain 126:1079–1091
Magis D, Bruno MA, Fumal A, Gerardy PY, Hustinx R, Laureys S, Schoenen J (2011) Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study. BMC Neurol 11:25. doi:10.1186/1471-2377-11-25
Marangolo P, Fiori V, Calpagnano MA, Campana S, Razzano C, Caltagirone C, Marini A (2013) tDCS over the left inferior frontal cortex improves speech production in aphasia. Front Hum Neurosci 7:539. doi:10.3389/fnhum.2013.00539
Marlow NM, Bonilha HS, Short EB (2013) Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. Pain Pract 13:131–145. doi:10.1111/j.1533-2500.2012.00562.x
Matharu MS, Bartsch T, Ward N, Frackowiak RS, Weiner R, Goadsby PJ (2004) Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study. Brain 127:220–230. doi:10.1093/brain/awh022
Mendonca ME, Simis M, Grecco LC, Battistella LR, Baptista AF, Fregni F (2016) Transcranial direct current stimulation combined with aerobic exercise to optimize analgesic responses in fibromyalgia: a randomized placebo-controlled clinical trial. Front Hum Neurosci 10:68. doi:10.3389/fnhum.2016.00068
Miranda PC, Lomarev M, Hallett M (2006) Modeling the current distribution during transcranial direct current stimulation. Clin Neurophysiol 117:1623–1629. doi:10.1016/j.clinph.2006.04.009
Montoya P, Sitges C, Garcia-Herrera M, Rodriguez-Cotes A, Izquierdo R, Truyols M, Collado D (2006) Reduced brain habituation to somatosensory stimulation in patients with fibromyalgia. Arthritis Rheum 54:1995–2003. doi:10.1002/art.21910
Nahmias F, Debes C, de Andrade DC, Mhalla A, Bouhassira D (2009) Diffuse analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers. Pain 147:224–232. doi:10.1016/j.pain.2009.09.016
Napadow V, Kim J, Clauw DJ, Harris RE (2012) Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. Arthritis Rheum 64:2398–2403. doi:10.1002/art.34412
Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527(Pt 3):633–639
Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W (2003) Modulation of cortical excitability by weak direct current stimulation—technical, safety and functional aspects. Suppl Clin Neurophysiol 56:255–276
Nordin LE, Moller MC, Julin P, Bartfai A, Hashim F, Li TQ (2016) Post mTBI fatigue is associated with abnormal brain functional connectivity. Sci Rep 6:21183. doi:10.1038/srep21183
Nuesch E, Hauser W, Bernardy K, Barth J, Juni P (2013) Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis. Ann Rheum Dis 72:955–962. doi:10.1136/annrheumdis-2011-201249
Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N (2004) Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol 4:14. doi:10.1186/1471-2377-4-14
O’Reardon JP, Solvason HB, Janicak PG et al (2007) Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 62:1208–1216. doi:10.1016/j.biopsych.2007.01.018
Osman A, Barrios FX, Kopper BA, Hauptmann W, Jones J, O’Neill E (1997) Factor structure, reliability, and validity of the Pain Catastrophizing Scale. J Behav Med 20:589–605
Pardini M, Bonzano L, Mancardi GL, Roccatagliata L (2010) Frontal networks play a role in fatigue perception in multiple sclerosis. Behav Neurosci 124:329–336. doi:10.1037/a0019585
Plazier M, Dekelver I, Vanneste S, Stassijns G, Menovsky T, Thimineur M, De Ridder D (2014) Occipital nerve stimulation in fibromyalgia: a double-blind placebo-controlled pilot study with a six-month follow-up. Neuromodulation 17:256–263. doi:10.1111/ner.12121 (discussion 263–254)
Plazier M, Ost J, Stassijns G, De Ridder D, Vanneste S (2015a) C2 nerve field stimulation for the treatment of fibromyalgia: a prospective, double-blind, randomized, controlled cross-over study. Brain Stimul 8:751–757. doi:10.1016/j.brs.2015.03.002
Plazier M, Ost J, Stassijns G, De Ridder D, Vanneste S (2015b) C2 nerve field stimulation for the treatment of fibromyalgia: a prospective, double-blind, randomized, controlled cross-over study. Brain Stimul 8:751–757. doi:10.1016/j.brs.2015.03.002
Plazier M, Tchen S, Ost J, Joos K, De Ridder D, Vanneste S (2015c) Is transcranial direct current stimulation an effective predictor for invasive occipital nerve stimulation treatment success in fibromyalgia Patients? Neuromodulation 18:623–629. doi:10.1111/ner.12340 (discussion 629)
Pujol J, Macia D, Garcia-Fontanals A et al (2014) The contribution of sensory system functional connectivity reduction to clinical pain in fibromyalgia. Pain 155:1492–1503. doi:10.1016/j.pain.2014.04.028
Riberto M, Marcon Alfieri F, de Benedetto Monteiro, Pacheco K, Dini Leite V, Nemoto Kaihami H, Fregni F, Rizzo Battistella L (2011) Efficacy of transcranial direct current stimulation coupled with a multidisciplinary rehabilitation program for the treatment of fibromyalgia. Open Rheumatol J 5:45–50. doi:10.2174/1874312901105010045
Roelcke U, Kappos L, Lechner-Scott J et al (1997) Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 48:1566–1571
Roizenblatt S, Fregni F, Gimenez R et al (2007) Site-specific effects of transcranial direct current stimulation on sleep and pain in fibromyalgia: a randomized, sham-controlled study. Pain Pract 7:297–306. doi:10.1111/j.1533-2500.2007.00152.x
Roizenblatt S et al (2011) Site-specific Effects of Transcranial Direct Current Stimulation on Sleep and Pain in Fibromyalgia: A Randomized, Sham-controlled Study. Pain Pract 7:297–306
Saiote C, Goldschmidt T, Timaus C et al (2014) Impact of transcranial direct current stimulation on fatigue in multiple sclerosis. Restor Neurol Neurosci 32:423–436. doi:10.3233/RNN-130372
Sauer K, Kemper C, Glaeske G (2011) Fibromyalgia syndrome: prevalence, pharmacological and non-pharmacological interventions in outpatient health care. An analysis of statutory health insurance data. Joint Bone Spine 78:80–84. doi:10.1016/j.jbspin.2010.05.003
Sepulcre J, Masdeu JC, Goni J, Arrondo G, Velez de Mendizabal N, Bejarano B, Villoslada P (2009) Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways. Mult Scler 15:337–344. doi:10.1177/1352458508098373
Stagg CJ, Bachtiar V, O’Shea J et al (2012) Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke. Brain 135:276–284. doi:10.1093/brain/awr313
Theadom A, Cropley M (2008) Dysfunctional beliefs, stress and sleep disturbance in fibromyalgia. Sleep Med 9:376–381. doi:10.1016/j.sleep.2007.06.005
Thimineur M, De Ridder D (2007) C2 area neurostimulation: a surgical treatment for fibromyalgia. Pain Med 8:639–646. doi:10.1111/j.1526-4637.2007.00365.x
Valle A, Roizenblatt S, Botte S et al (2009) 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 2:353–361
Vanneste S, Plazier M, Ost J, van der Loo E, Van de Heyning P, De Ridder D (2010) Bilateral dorsolateral prefrontal cortex modulation for tinnitus by transcranial direct current stimulation: a preliminary clinical study. Exp Brain Res 202:779–785. doi:10.1007/s00221-010-2183-9
Villamar MF, Wivatvongvana P, Patumanond J, Bikson M, Truong DQ, Datta A, Fregni F (2013) Focal modulation of the primary motor cortex in fibromyalgia using 4x1-ring high-definition transcranial direct current stimulation (HD-tDCS): immediate and delayed analgesic effects of cathodal and anodal stimulation. J Pain 14:371–383. doi:10.1016/j.jpain.2012.12.007
Wolfe F, Smythe HA, Yunus MB et al (1990) The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 33:160–172
Zhu CE, Yu B, Zhang W, Chen WH, Qi Q, Miao Y (2017) Effiectiveness and safety of transcranial direct current stimulation in fibromyalgia: a systematic review and meta-analysis. J Rehabil Med 49:2–9. doi:10.2340/16501977-2179
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To, W.T., James, E., Ost, J. et al. Differential effects of bifrontal and occipital nerve stimulation on pain and fatigue using transcranial direct current stimulation in fibromyalgia patients. J Neural Transm 124, 799–808 (2017). https://doi.org/10.1007/s00702-017-1714-y
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DOI: https://doi.org/10.1007/s00702-017-1714-y