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Current Pain and Headache Reports

, Volume 16, Issue 5, pp 388–398 | Cite as

Brain Imaging in Fibromyalgia

  • Liliana Lourenço JorgeEmail author
  • Edson AmaroJr.
Fibromyalgia (MFP Peres, Section Editor)

Abstract

Fibromyalgia is a primary brain disorder or a result of peripheral dysfunctions inducing brain alterations, with underlying mechanisms that partially overlap with other painful conditions. Although there are methodologic variations, neuroimaging studies propose neural correlations to clinical findings of abnormal pain modulation in fibromyalgia. Growing evidences of specific differences of brain activations in resting states and pain-evoked conditions confirm clinical hyperalgesia and impaired inhibitory descending systems, and also demonstrate cognitive-affective influences on painful experiences, leading to augmented pain-processing. Functional data of neural activation abnormalities parallel structural findings of gray matter atrophy, alterations of intrinsic connectivity networks, and variations in metabolites levels along multiple pathways. Data from positron-emission tomography, single-photon-emission-computed tomography, blood-oxygen-level-dependent, voxel-based morphometry, diffusion tensor imaging, default mode network analysis, and spectroscopy enable the understanding of fibromyalgia pathophysiology, and favor the future establishment of more tailored treatments.

Keywords

Fibromyalgia Magnetic resonance imaging Chronic pain Postsynaptic potential summation Pain measurement Brain mapping Functional neuroimaging Tomography Emission-computed, single-photon Positron-emission tomography 

Notes

Acknowledgments

The authors thank Dr Mario Peres and Dr David Borsook (invitation), and Mara Beloni (proofreading).

Disclosures

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Russel IJ, Larson AA. Neurophysiopathogenesis of fibromyalgia syndrome: a unified hypothesis. Rheum Dis Clin North Am. 2009;35:421–35.CrossRefGoogle Scholar
  2. 2.
    Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RS, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol. 2011;38:1113–22.PubMedCrossRefGoogle Scholar
  3. 3.
    Cook DB, Steghner AJ, McLoughlin MJ. Imaging pain of fibromyalgia. Curr Pain Headache Rep. 2007;11:190–200.PubMedCrossRefGoogle Scholar
  4. 4.
    DeSantana JM, Sluka KA. Central mechanisms in the maintenance of chronic widespread noninflamatory muscle pain. Curr Pain Headache Rep. 2008;12:338–43.PubMedCrossRefGoogle Scholar
  5. 5.
    Staud R. Evidence of involvement of central neural mechanisms in generating fibromyalgia pain. Curr Rheumatol Rep. 2002;4:299–305.PubMedCrossRefGoogle Scholar
  6. 6.
    Schweinhardt P, Sauro KM, Bushnell MC. Fibromyalgia: a disorder of the brain? Neuroscientist. 2008;14:415–21.PubMedCrossRefGoogle Scholar
  7. 7.
    Becker S, Schweinhardt P. Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological action on these systems. Pain Res Treat. 2012;2012:741746.PubMedGoogle Scholar
  8. 8.
    Frank B, Niesler B, Bondy B, Späth M, Pongratz DE, Ackenheil M, et al. Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients. Clin Rheumatol. 2004;23:338–44.PubMedCrossRefGoogle Scholar
  9. 9.
    Borsook D, Becerra LR. Breaking down the barriers: fMRI applications in pain, analgesia and analgesics. Moll Pain. 2006;2:30.CrossRefGoogle Scholar
  10. 10.
    Schmidt-Wilcke T. Variations in brain volume and regional morphology associated to chronic pain. Curr Rheumatol Rep. 2008;10:467–74.PubMedCrossRefGoogle Scholar
  11. 11.
    Schmidt-Wilcke T, Luerding R, Weigand T, Jürgens T, Schuierer G, Leinisch E, et al. Striatal grey matter increase in patients suffering from fibromyalgia – a voxel-based morphometry study. Pain. 2007;132:S109–16.PubMedCrossRefGoogle Scholar
  12. 12.
    Ceko M, Buschnell C, Gracely RH. Neurobiology underlying fibromyalgia symptoms. Pain Res Treat. 2012;2012:585419.PubMedGoogle Scholar
  13. 13.
    Wood PB, Patterson JC II, Sunderland JJ, Tainter KH, Glabus MF, Lilien DL. Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study. Pain. 2007;8:51–8.CrossRefGoogle Scholar
  14. 14.
    Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, et al. Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci. 2007;25:3576–82.PubMedCrossRefGoogle Scholar
  15. 15.
    Schmidt-Wilcke T, Leinisch E, Straube A, et al. Gray matter decrease in patients with chronic tension type headache. Neurology. 2005;65:1483–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007;27:10000–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Wood PB, Patterson II JC, Jasmin LD. Insular hypometabolism in a patient with fibromyalgia: a case study. Pain Med. 2008;9:365–70.PubMedCrossRefGoogle Scholar
  18. 18.
    Wik G, Fischer H, Bragee B, Kristianson M, Fredrikson M. Retrosplenial cortical activation in the fibromyalgia syndrome. NeuroReport. 2003;14:619–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Iadarola MJ, Max MB, Berman KF, et al. Unilateral decrease in thalamic activity observed with positron emission tomography in patients with chronic neuropathic pain. Pain. 1995;63:55–64.PubMedCrossRefGoogle Scholar
  20. 20.
    Di Piero V, Jones AK, Iannotti F, Powell M, Perani D, Lenzi GL, et al. Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy. Pain. 1991;46:9–12.PubMedCrossRefGoogle Scholar
  21. 21.
    Ness TJ, San Pedro EC, Richards JS, Kezar L, Liu HG, Mountz JM. A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin. Pain. 1998;78:139–43.Google Scholar
  22. 22.
    Mountz JM, Bradley LA, Modell JG, Alexander RW, Triana-Alexander M, Aaron LA, et al. Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. 1995;38:926–38.PubMedCrossRefGoogle Scholar
  23. 23.
    Kwiatek R, Barnden L, Tedman R, Jarrett R, Chew J, Rowe C, et al. Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in teh pontine tegmentum and thalami. Arthritis Rheum. 2000;43:2823–33.PubMedCrossRefGoogle Scholar
  24. 24.
    Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9:463–84.PubMedCrossRefGoogle Scholar
  25. 25.
    Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002;46:1333–43.PubMedCrossRefGoogle Scholar
  26. 26.
    Giesecke T, Gracely RH, Grant MA, et al. Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum. 2004;50:613–23.PubMedCrossRefGoogle Scholar
  27. 27.
    Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH. Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol. 2004;31:364–78.PubMedGoogle Scholar
  28. 28.
    Williams DA, Gracely RH. Biology and therapy of fibromyalgia: functional magnetic resonance imaging findings in fibromyalgia. Arthritis Res Ther. 2006;8:224.PubMedCrossRefGoogle Scholar
  29. 29.
    Staud R, Craggs JG, Perlstein WM, et al. Brain activity associated with slow temporal summation of C-fiber evoked pain in fibromyalgia patients and healthy controls. Eur J Pain. 2008;12:1078–89.PubMedCrossRefGoogle Scholar
  30. 30.
    Kim SH, Chang Y, Kim JH, et al. Insular cortex is a trait marker for pain processing in fibromyalgia syndrome—blood oxigenation level-dependent functional magnetic resonance imaging study in Korea. Clin Exp Rheumatol. 2011;29:S19–27.PubMedGoogle Scholar
  31. 31.
    Kang DH, Son JH, Yong CK. Neuroimaging studies of chronic pain. Korean J Pain. 2010;23:159–65.CrossRefGoogle Scholar
  32. 32.
    Staud R. Brain imaging in fibromyalgia syndrome. Clin Exp Rheumatol. 2011;29:S109–17.PubMedGoogle Scholar
  33. 33.
    Jensen KB, Kosek E, Petzke F, et al. Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain. Pain. 2009;144:95–100.PubMedCrossRefGoogle Scholar
  34. 34.
    Giesecke T, Gracely RH, Williams DA, Geisser M, Petzke F, et al. The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis Rheum. 2005;52:1577–84.PubMedCrossRefGoogle Scholar
  35. 35.
    Gracely RH, Geisser ME, Giesecke T, et al. Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain. 2004;127:835–43.PubMedCrossRefGoogle Scholar
  36. 36.
    Nebel MB, Gracely RH. Neuroimaging of fibromyalgia. Rheum Dis Clin N Am. 2009;35:313–27.CrossRefGoogle Scholar
  37. 37.
    Torres X, Collado A, Arias A, Peri JM, Bailles E, et al. Pain locus of control predicts return to work among Spanish fibromyalgia patients after completion of a multidisciplinary pain program. Gen Hosp Psychiatry. 2009;31:137–45.PubMedCrossRefGoogle Scholar
  38. 38.
    Pastor MA, Salas E, López S, Rodríguez J, Sánchez S, et al. Patients' beliefs about their lack of pain control in primary fibromyalgia syndrome. Br J Rheumatol. 1993;32:484–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Burton AK, Tillotson KM, Main CJ, Hollis S. Psychosocial predictors of outcome in acute and subchronic low back trouble. Spine. 1995;20:722–28.PubMedCrossRefGoogle Scholar
  40. 40.
    • Burgmer M, Pogatzki-Zahn E, Gaubitz M, et al. Fibromyalgia unique temporal brain activation during experimental pain: a controlled fMRI Study. J Neural Transm. 2010;117:123–31. This study uses a factorial design of continuous pain stimulation to verify anticipation mechanisms associated with pain, and also nociception over time.Google Scholar
  41. 41.
    Burgmer M, Pogatzki-Zahn E, Gaubitz M, et al. Altered brain activity during pain processing in fibromyalgia. NeuroImage. 2009;44:502–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Jorge LL, Gerard C, Revel M. Evidences of memory dysfunction and maladaptive coping in chronic low back pain and rheumatoid patients: challenges for rehabilitation. Eur J Phys Rehab Med. 2009;45:469–77.Google Scholar
  43. 43.
    Park DC, Glass JM, Minear M, Crofford LJ. Cognitive function in fibromyalgia patients. Arthritis Rheum. 2001;44:2125–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Dick BD, Verrier MJ, Harker KT, Rashiq S. Disruption of cognitive function in fibromyalgia syndrome. Pain. 2008;139:610–16.PubMedCrossRefGoogle Scholar
  45. 45.
    García-Campayo J, Fayed N, Serrano-Blanco A, Roca M. Brain dysfunction behind functional symptoms: neuroimaging and somatoform, conversive and dissociative disorders. Curr Opin Psychiatry. 2009;22:224–31.PubMedCrossRefGoogle Scholar
  46. 46.
    Harris RE. Elevated excitatory neurotransmitter levels in the fibromyalgia brain. Arthritis Res Ther. 2010;12:141.PubMedCrossRefGoogle Scholar
  47. 47.
    Harris RE, Sundgren PC, Craig AD, et al. Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis Rheum. 2009;60:3146–52.PubMedCrossRefGoogle Scholar
  48. 48.
    Harris RE, Sundgren PC, Pang Y. Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia. Arthritis Rheum. 2008;58:903–7.PubMedCrossRefGoogle Scholar
  49. 49.
    • Fayed N, Garcia-Campayo J, Magallón R, et al. Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate. Arthritis Res Ther. 2010;12:R134. This study uses 3 techniques (HMRS, DTI, and DWI) to demonstrate that Glx may be a pathological factor in FM. This is one of the first studies combining new fMRI techniques for the understanding of FM pathophysiology.Google Scholar
  50. 50.
    Valdés M, Collado A, Bargalló N, et al. Increased glutamate/glutamine compounds in the brain of patients with fibromialgia: a magnetic resonance spectroscopy study. Arthritis Rheum. 2010;62:1829–36.PubMedCrossRefGoogle Scholar
  51. 51.
    Silverstone PH, McGrath BM, Kim H. Bipolar disorder and myo-inositol: a review of the magnetic resonance spectroscopy findings. Bipolar Disord. 2005;7:1–10.PubMedCrossRefGoogle Scholar
  52. 52.
    Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CSN Neurol Disord Drug Targets. 2007;6:219–33.CrossRefGoogle Scholar
  53. 53.
    Cordoba J, Blei AT. Brain edema and hepatic encephalopathy. Semin Liver Dis. 1996;16:271–80.PubMedCrossRefGoogle Scholar
  54. 54.
    • Robinson MC, Craggs JG, Price DD, Perlstein WM, Staud R.Gray matter volumes of pain-related brain areas are decreased in fibromyalgia syndrome. J Pain. 2011;12:436–43. Gray matter atrophy has been a controversy among the VBM studies. Using a more stringent analysis, this study provides evidence of gray matter loss in sensory-affective, pain-related areas.Google Scholar
  55. 55.
    Davis KD, Pope G, Chen J, et al. Cortical thinning in IBS: implications for homeostatic, attention, and pain processing. Neurology. 2008;70:153–4.PubMedCrossRefGoogle Scholar
  56. 56.
    May A. Chronic pain may change the structure of the brain. Brain. 2008;137:7–15.Google Scholar
  57. 57.
    Kuchinad A, Schweinhardt P, Seminowicz DA, et al. Accelerated brain Gray matter loss in fibromyalgia patients: premature aging of the brain? Neurosci. 2007;27:4004–7.CrossRefGoogle Scholar
  58. 58.
    Burgmer M, Gaubiz M, Konrad C, et al. Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia. Psychosom Med. 2009;71:566–73.PubMedCrossRefGoogle Scholar
  59. 59.
    Schmidt-Wilke TLR, Weigand T, et al. Striatal grey matter increase in patients suffering from fibromyalgia -a voxel-based morphometry study. Pain. 2007;132:S109–16.CrossRefGoogle Scholar
  60. 60.
    Luerding R, Weigand T, Bogdahn U, Schmidt-Wilke T. Working memory performance us correlated with local brain morphology in the medial frontal and anterior cingulate cortex in fibromyalgia patients: structural correlates of pain-cognition interaction. Brain. 2008;131:3222–31.PubMedCrossRefGoogle Scholar
  61. 61.
    Apkarian AV, Sosa Y, Krauss BR, et al. Chronic back pain is associated with decrease prefrontal and thalamic gray matter density. J Neurosci. 2004;24:10410–15.PubMedCrossRefGoogle Scholar
  62. 62.
    • Du MY, Wu QZ, Yue Q, et al. Voxelwise meta-analysis of gray matter reduction in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2012;36:11–16. A voxel-wise meta-analysis of gray matter loss is possible in patients with fibromyalgia, considering the findings from several works so far. This study is relevant in terms of methodological approach, and also because affective disorders and fibromyalgia share clinical features and neural substrates to some degree.Google Scholar
  63. 63.
    Hsu MC, Harris RE, Sundgren PC, et al. No consistent difference in gray matter volume between individuals with fibromyalgia and age-matched healthy subjects when controlling for affective disorder. Pain. 2009;143:262–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Regland B, Andersson M, Abrahamsson L, et al. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol. 1997;26:301–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Cauda F, D'Agata F, Sacco K, Duca S, Cocito D, et al. Altered resting state attentional networks in diabetic neuropathic pain. J Neurol Neurosurg Psychiatry. 2010;81:806–11.PubMedCrossRefGoogle Scholar
  66. 66.
    • Napadow V, LaCount L, Park K, et al. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum. 2010;62:2545–88. This is one of the first resting-state fMRI studies for the analysis of intrinsic connectivity in FM, and shows that resting-brain activity, spontaneous pain, and impairment of multiple networks may corroborate other biochemical and structural findings.Google Scholar
  67. 67.
    Ibañez A, Gleichgerrcht E, Manes F. Clinical effects of insular damage in humans. Brain Struct Funct. 2010;214:397–410.PubMedCrossRefGoogle Scholar
  68. 68.
    Lutz J, Jäger L, de Quervain D, et al. White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study. Arthritis Rheum. 2008;58:3960–69.PubMedCrossRefGoogle Scholar
  69. 69.
    Sundgren PC, Petrou M, Harris RE, et al. Diffusion-weighted and diffusion tensor imaging in fibromyalgia patients: a prospective study of whole brain diffusivity, apparent diffusion coefficient, and fraction anisotropy in different regions of the brain and correlation with symptom severity. Acad Radiol. 2007;14:839–46.PubMedCrossRefGoogle Scholar
  70. 70.
    Owen DG, Bureau Y, Thomas AW, et al. Quantification of pain-induced changes in cerebral blood flow by perfusion MRI. Pain. 2008;136:85–96.PubMedCrossRefGoogle Scholar
  71. 71.
    Foerster BR, Petrou M, Harris RE, et al. Cerebral blood flow alterations in pain-processing regions of patients with fibromyalgia using perfusion MR imaging. AJNR Am J Neuroradiol. 2011;32:1873–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Adigüzel O, Kaptanoglu E, Turgut B, Nacitarhan V. The possible effect of clinical recovery on regional cerebral blood flow deficits in fibromyalgia: a prospective study with semiquantitative SPECT. South Med J. 2004;97:651–5.PubMedCrossRefGoogle Scholar
  73. 73.
    Usui C, Doi N, Nishioka M, et al. Electroconvulsive therapy improves severe pain associated with fibromyalgia. Pain. 2006;121:276–80.PubMedCrossRefGoogle Scholar
  74. 74.
    • Usui C, Hatta K, Doi N, et al. Brain perfusion in fibromyalgia patients and its differences between responders and poor responders to gabapentin. Arthritis Res Ther. 2010;12:R64. This study follows a recent tendency to use neuroimaging as an objective instrument for measuring a treatment’s efficacy.Google Scholar
  75. 75.
    Mainguy Y. Functional Magnetic resonance imagery (fMRI) in fibromyalgia and the response to milnacipran. Hum Psychopharmacol. 2009;24:S19–23.PubMedCrossRefGoogle Scholar
  76. 76.
    Morris LD, Grimmer-Somers KA, Spottiswoode B, Louw QA. Virtual reality exposure therapy as treatment for pain catastrophizing in fibromyalgia patients: proof-of-concept study (Study Protocol). BMC Musculoskelet Disord. 2011;12:85.PubMedCrossRefGoogle Scholar
  77. 77.
    deCharms RC, Maeda F, Glover GH, Ludlow D, Pauly JM, Soneji D, et al. Control over brain activation and pain learned by using real-time functional MRI. Proc Natl Acad Sci USA. 2005;102(51):18626–31.Google Scholar
  78. 78.
    Walitt B, Roebuck-Spencer T, Esposito G, et al. The effects of multidisciplinary therapy on positron emission tomography of the brain in fibromyalgia: a pilot study. Rheumatol Int. 2007;27:1019–24.PubMedCrossRefGoogle Scholar
  79. 79.
    Schmidt-Wilke T, Clauw DJ. Fibromyalgia: from pathophysiology to therapy. Nat Rev Rheumatol. 2011;7:518–27.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Hospital Israelita Albert Einstein and Instituto de Reabilitação “Lucy Montoro”MorumbiBrazil
  2. 2.Instituto do Cérebro, Hospital Israelita Albert EinsteinMorumbiBrazil
  3. 3.Department of RadiologyUniversity of Sao PauloSao PauloBrazil

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