Skip to main content

Advertisement

SpringerLink
Log in

Brain Imaging in Fibromyalgia

  • Fibromyalgia (MFP Peres, Section Editor)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

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

  1. Russel IJ, Larson AA. Neurophysiopathogenesis of fibromyalgia syndrome: a unified hypothesis. Rheum Dis Clin North Am. 2009;35:421–35.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  3. Cook DB, Steghner AJ, McLoughlin MJ. Imaging pain of fibromyalgia. Curr Pain Headache Rep. 2007;11:190–200.

    Article  PubMed  Google Scholar 

  4. DeSantana JM, Sluka KA. Central mechanisms in the maintenance of chronic widespread noninflamatory muscle pain. Curr Pain Headache Rep. 2008;12:338–43.

    Article  PubMed  Google Scholar 

  5. Staud R. Evidence of involvement of central neural mechanisms in generating fibromyalgia pain. Curr Rheumatol Rep. 2002;4:299–305.

    Article  PubMed  Google Scholar 

  6. Schweinhardt P, Sauro KM, Bushnell MC. Fibromyalgia: a disorder of the brain? Neuroscientist. 2008;14:415–21.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  9. Borsook D, Becerra LR. Breaking down the barriers: fMRI applications in pain, analgesia and analgesics. Moll Pain. 2006;2:30.

    Article  Google Scholar 

  10. Schmidt-Wilcke T. Variations in brain volume and regional morphology associated to chronic pain. Curr Rheumatol Rep. 2008;10:467–74.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  12. Ceko M, Buschnell C, Gracely RH. Neurobiology underlying fibromyalgia symptoms. Pain Res Treat. 2012;2012:585419.

    PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  17. Wood PB, Patterson II JC, Jasmin LD. Insular hypometabolism in a patient with fibromyalgia: a case study. Pain Med. 2008;9:365–70.

    Article  PubMed  Google Scholar 

  18. Wik G, Fischer H, Bragee B, Kristianson M, Fredrikson M. Retrosplenial cortical activation in the fibromyalgia syndrome. NeuroReport. 2003;14:619–21.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  28. Williams DA, Gracely RH. Biology and therapy of fibromyalgia: functional magnetic resonance imaging findings in fibromyalgia. Arthritis Res Ther. 2006;8:224.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  31. Kang DH, Son JH, Yong CK. Neuroimaging studies of chronic pain. Korean J Pain. 2010;23:159–65.

    Article  Google Scholar 

  32. Staud R. Brain imaging in fibromyalgia syndrome. Clin Exp Rheumatol. 2011;29:S109–17.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  36. Nebel MB, Gracely RH. Neuroimaging of fibromyalgia. Rheum Dis Clin N Am. 2009;35:313–27.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

  41. Burgmer M, Pogatzki-Zahn E, Gaubitz M, et al. Altered brain activity during pain processing in fibromyalgia. NeuroImage. 2009;44:502–8.

    Article  PubMed  Google Scholar 

  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. Park DC, Glass JM, Minear M, Crofford LJ. Cognitive function in fibromyalgia patients. Arthritis Rheum. 2001;44:2125–33.

    Article  PubMed  CAS  Google Scholar 

  44. Dick BD, Verrier MJ, Harker KT, Rashiq S. Disruption of cognitive function in fibromyalgia syndrome. Pain. 2008;139:610–16.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  46. Harris RE. Elevated excitatory neurotransmitter levels in the fibromyalgia brain. Arthritis Res Ther. 2010;12:141.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  52. Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CSN Neurol Disord Drug Targets. 2007;6:219–33.

    Article  CAS  Google Scholar 

  53. Cordoba J, Blei AT. Brain edema and hepatic encephalopathy. Semin Liver Dis. 1996;16:271–80.

    Article  PubMed  CAS  Google Scholar 

  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.

  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.

    Article  PubMed  CAS  Google Scholar 

  56. May A. Chronic pain may change the structure of the brain. Brain. 2008;137:7–15.

    Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

  67. Ibañez A, Gleichgerrcht E, Manes F. Clinical effects of insular damage in humans. Brain Struct Funct. 2010;214:397–410.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  73. Usui C, Doi N, Nishioka M, et al. Electroconvulsive therapy improves severe pain associated with fibromyalgia. Pain. 2006;121:276–80.

    Article  PubMed  Google Scholar 

  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.

  75. Mainguy Y. Functional Magnetic resonance imagery (fMRI) in fibromyalgia and the response to milnacipran. Hum Psychopharmacol. 2009;24:S19–23.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  79. Schmidt-Wilke T, Clauw DJ. Fibromyalgia: from pathophysiology to therapy. Nat Rev Rheumatol. 2011;7:518–27.

    Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Hospital Israelita Albert Einstein and Instituto de Reabilitação “Lucy Montoro”, Avenida Albert Einstein, 627 3rd Floor Block D, 05651901, Morumbi, Sao Paulo, Brazil

    Liliana Lourenço Jorge

  2. Instituto do Cérebro, Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627 4th Floor Block D, 05651901, Morumbi, Sao Paulo, Brazil

    Edson Amaro Jr.

  3. Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil

    Edson Amaro Jr.

Authors
  1. Liliana Lourenço Jorge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edson Amaro Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liliana Lourenço Jorge.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jorge, L.L., Amaro, E. Brain Imaging in Fibromyalgia. Curr Pain Headache Rep 16, 388–398 (2012). https://doi.org/10.1007/s11916-012-0284-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-012-0284-9

Keywords

Search

Navigation