Neuroimaging Studies of Somatoform Pain Disorder: How Far Have We Come?

  • Atsuo Yoshino
  • Yasumasa Okamoto
  • Shigeto Yamawaki


We review neuroimaging studies for somatoform pain disorder. It is important for studies of somatoform pain disorder to assess various psychosocial elements as well as somatic complaints per se. Multidimensional understandings are crucial for development of useful etiological models and treatment approaches. The brain regions altered in somatoform pain disorder appear to include the ACC, insula, amygdala, hippocampus, parahippocampus, SI, SII, basal ganglia, and PFC. We believe that negative psychosocial factors and restricted emotional responses are linked to such brain-based findings, and various studies have supported such relationships. However, somatoform pain disorder neuroimaging studies remain few and far between, and further study is needed to elucidate the relationship between pathophysiology in somatoform pain disorder and the associated brain mechanisms.


Insula Behavior Pain perception Fibromyalgia Parahippocampus Hemodynamic Psychosocial 


  1. 1.
    APA. Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Publishing Inc.; 1994.Google Scholar
  2. 2.
    APA. Diagnostic and statistical manual of mental disorders, (DSM-5®). American Psychiatric Publishing; 2013.Google Scholar
  3. 3.
    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.CrossRefPubMedGoogle Scholar
  4. 4.
    Atmaca M, Sirlier B, Yildirim H, Kayali A. Hippocampus and amygdalar volumes in patients with somatization disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(7):1699–703.CrossRefPubMedGoogle Scholar
  5. 5.
    Baliki MN, Petre B, Torbey S, Herrmann KM, Huang L, Schnitzer TJ, et al. Corticostriatal functional connectivity predicts transition to chronic back pain. Nat Neurosci. 2012;15(8):1117–9.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Barsky AJ, Goodson JD, Lane RS, Cleary PD. The amplification of somatic symptoms. Psychosom Med. 1988;50(5):510–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Bleich S, Römer K, Wiltfang J, Kornhuber J. Glutamate and the glutamate receptor system: a target for drug action. Int J Geriatr Psychiatry. 2003;18(S1):S33–40.CrossRefPubMedGoogle Scholar
  8. 8.
    Bushnell MC, Čeko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013;14(7):502–11.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Christopher deCharms R, 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 Nat Acad Sci USA. 2005;102(51):18626–31.Google Scholar
  10. 10.
    Coen SJ, Aziz Q, Yágüez L, Brammer M, Williams SC, Gregory LJ. Effects of attention on visceral stimulus intensity encoding in the male human brain. Gastroenterology. 2008;135(6):2065–74. e1.Google Scholar
  11. 11.
    Craig AB. How do you feel–now? The anterior insula and human awareness. Nat Rev Neurosci. 2009;10:59–70.CrossRefPubMedGoogle Scholar
  12. 12.
    Damasio AR, Grabowski TJ, Bechara A, Damasio H, Ponto LL, Parvizi J, et al. Subcortical and cortical brain activity during the feeling of self-generated emotions. Nat Neurosci. 2000;3(10):1049–56.CrossRefPubMedGoogle Scholar
  13. 13.
    de Greck M, Bölter AF, Lehmann L, Ulrich C, Stockum E, Enzi B et al. Changes in brain activity of somatoform disorder patients during emotional empathy after multimodal psychodynamic psychotherapy. Front Hum Neurosci. 2013;7.Google Scholar
  14. 14.
    de Greck M, Scheidt L, Bölter AF, Frommer J, Ulrich C, Stockum E, et al. Altered brain activity during emotional empathy in somatoform disorder. Hum Brain Mapp. 2012;33(11):2666–85.CrossRefPubMedGoogle Scholar
  15. 15.
    Dickenson AH, Matthews EA, Suzuki R. Neurobiology of neuropathic pain: mode of action of anticonvulsants. Eur J Pain. 2002;6(SA):51–60.Google Scholar
  16. 16.
    Fayed N, Andres E, Rojas G, Moreno S, Serrano-Blanco A, Roca M, et al. Brain dysfunction in fibromyalgia and somatization disorder using proton magnetic resonance spectroscopy: a controlled study. Acta Psychiatr Scand. 2012;126(2):115–25.CrossRefPubMedGoogle Scholar
  17. 17.
    Fayed N, Olmos S, Morales H, Modrego PJ. Physical basis of magnetic resonance spectroscopy and its application to central nervous system diseases. Am J Appl Sci. 2006;3(5):1836.CrossRefGoogle Scholar
  18. 18.
    Fink P, Hansen MS, Oxhoj M-L. The prevalence of somatoform disorders among internal medical inpatients. J Psychosom Res. 2004;56(4):413–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Gündel H, Valet M, Sorg C, Huber D, Zimmer C, Sprenger T, et al. Altered cerebral response to noxious heat stimulation in patients with somatoform pain disorder. Pain. 2008;137(2):413–21.CrossRefPubMedGoogle Scholar
  20. 20.
    Galhardoni R, Correia GS, Araujo H, Yeng LT, Fernandes DT, Kaziyama HH, et al. Repetitive transcranial magnetic stimulation in chronic pain: a review of the literature. Arch Phys Med Rehabil. 2015;96(4):S156–72.CrossRefPubMedGoogle Scholar
  21. 21.
    Garcia-Campayo J, Sanz-Carrillo C, Baringo T, Ceballos C. SPECT scan in somatization disorder patients: an exploratory study of eleven cases. Aust NZJ Psychiatry. 2001;35(3):359–63.CrossRefGoogle Scholar
  22. 22.
    Hakala M, Karlsson H, Kurki T, Aalto S, Koponen S, Vahlberg T, et al. Volumes of the caudate nuclei in women with somatization disorder and healthy women. Psychiatry Res Neuroimaging. 2004;131(1):71–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Hakala M, Vahlberg T. NIEMI PM, Karlsson H. Brain glucose metabolism and temperament in relation to severe somatization. Psychiatry Clin Neurosci. 2006; 60(6):669–75.CrossRefPubMedGoogle Scholar
  24. 24.
    Karibe H, Arakawa R, Tateno A, Mizumura S, Okada T, Ishii T, et al. Regional cerebral blood flow in patients with orally localized somatoform pain disorder: a single photon emission computed tomography study. Psychiatry Clin Neurosci. 2010;64(5):476–82.CrossRefPubMedGoogle Scholar
  25. 25.
    Koh KB, Sohn S-H, Kang JI. Lee Y-j, Lee JD. Relationship between neural activity and immunity in patients with undifferentiated somatoform disorder. Psychiatry Res Neuroimaging. 2012;202(3):252–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Kroenke K. Patients presenting with somatic complaints: epidemiology, psychiatric co-morbidity and management. Int J Methods Psychiatr Res. 2003;12(1):34–43.CrossRefPubMedGoogle Scholar
  27. 27.
    Kroenke K. Efficacy of treatment for somatoform disorders: a review of randomized controlled trials. Psychosom Med. 2007;69(9):881–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Lane RD, Carmichael C, Reis HT. Differentiation in the momentary rating of somatic symptoms covaries with trait emotional awareness in patients at risk for sudden cardiac death. Psychosom Med. 2011;73(2):185–92.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Lipowski ZJ. Somatization: the concept and its clinical application. Am J Psychiatry. 1988;145(11):1358–68.CrossRefPubMedGoogle Scholar
  30. 30.
    Mohr C, Leyendecker S, Mangels I, Machner B, Sander T, Helmchen C. Central representation of cold-evoked pain relief in capsaicin induced pain: an event-related fMRI study. Pain. 2008;139(2):416–30.CrossRefPubMedGoogle Scholar
  31. 31.
    Morgan V, Pickens D, Gautam S, Kessler R, Mertz H. Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome. Gut. 2005;54(5):601–7.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Muller JE, Wentzel I, Nel DG, Stein DJ. Depression and anxiety in multisomatoform disorder: Prevalence and clinical predictors in primary care. SAMJ S Afr Med J. 2008;98(6):473–6.PubMedGoogle Scholar
  33. 33.
    Niemi P, Portin R, Aalto S, Hakala M, Karlsson H. Cognitive functioning in severe somatization—a pilot study. Acta Psychiatr Scand. 2002;106(6):461–3.CrossRefPubMedGoogle Scholar
  34. 34.
    Noll-Hussong M, Otti A, Laeer L, Wohlschlaeger A, Zimmer C, Lahmann C, et al. Aftermath of sexual abuse history on adult patients suffering from chronic functional pain syndromes: an fMRI pilot study. J Psychosom Res. 2010;68(5):483–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Noll-Hussong M, Otti A, Wohlschlaeger AM, Zimmer C, Henningsen P, Lahmann C, et al. Neural correlates of deficits in pain-related affective meaning construction in patients with chronic pain disorder. Psychosom Med. 2013;75(2):124–36.CrossRefPubMedGoogle Scholar
  36. 36.
    Ochsner KN, Ludlow DH, Knierim K, Hanelin J, Ramachandran T, Glover GC, et al. Neural correlates of individual differences in pain-related fear and anxiety. Pain. 2006;120:69–77.CrossRefPubMedGoogle Scholar
  37. 37.
    Otti A, Guendel H, Wohlschläger A, Zimmer C, Noll-Hussong M. Frequency shifts in the anterior default mode network and the salience network in chronic pain disorder. BMC Psychiatry. 2013;13(1):84–92.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Pedrosa Gil F, Ridout N, Kessler H, Neuffer M, Schoechlin C, Traue HC et al. Facial emotion recognition and alexithymia in adults with somatoform disorders. Depress Anxiety. 2009;26(1):E26–E33.Google Scholar
  39. 39.
    Perahia DG, Pritchett YL, Desaiah D, Raskin J. Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect? Int Clin Psychopharmacol. 2006;21(6):311–7.CrossRefPubMedGoogle Scholar
  40. 40.
    Perez DL, Barsky AJ, Vago DR, Baslet G, Silbersweig DA. A neural circuit framework for somatosensory amplification in somatoform disorders. J Neuropsychiatry Clinic Neurosci. 2015.Google Scholar
  41. 41.
    Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain responses to pain. A review and meta-analysis. Clinic Neurophysiol. 2000;30:263–88. S0987-7053(00)00227-6 [pii].Google Scholar
  42. 42.
    Phillips K, Clauw DJ. Central pain mechanisms in chronic pain states–maybe it is all in their head. Best Pract Res Clin Rheumatol. 2011;25(2):141–54.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiat. 2003;54(5):504–14.CrossRefPubMedGoogle Scholar
  44. 44.
    Price DD. Central neural mechanisms that interrelate sensory and affective dimensions of pain. Mol Interv. 2002;2:392–403.CrossRefPubMedGoogle Scholar
  45. 45.
    Sadock BJ, Sadock VA. Synopsis of psychiatry. 2003.Google Scholar
  46. 46.
    Sawamoto N, Honda M, Okada T, Hanakawa T, Kanda M, Fukuyama H, et al. Expectation of pain enhances responses to nonpainful somatosensory stimulation in the anterior cingulate cortex and parietal operculum/posterior insula: an event-related functional magnetic resonance imaging study. J Neurosci. 2000;20(19):7438–45.PubMedGoogle Scholar
  47. 47.
    Smith GR Jr, Monson RA, Ray DC. Patients with multiple unexplained symptoms: their characteristics, functional health, and health care utilization. Arch Intern Med. 1986;146(1):69–72.CrossRefPubMedGoogle Scholar
  48. 48.
    Stefanie K, Peter A, Gerda S-Z, Marion F, Bernd S, Wolfgang P, et al. Dysfunctional pain modulation in somatoform pain disorder patients. Eur Arch Psychiatry Clin Neurosci. 2011;261(4):267–75.CrossRefPubMedGoogle Scholar
  49. 49.
    Stoeter P, Bauermann T, Nickel R, Corluka L, Gawehn J, Vucurevic G, et al. Cerebral activation in patients with somatoform pain disorder exposed to pain and stress: an fMRI study. Neuroimage. 2007;36(2):418–30.CrossRefPubMedGoogle Scholar
  50. 50.
    Su Q, Yao D, Jiang M, Liu F, Jiang J, Xu C, et al. Dissociation of regional activity in default mode network in medication-naive, first-episode somatization disorder. PLoS ONE. 2014;9(7):e99273.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Subic-Wrana C, Beutel ME, Knebel A, Lane RD. Theory of mind and emotional awareness deficits in patients with somatoform disorders. Psychosom Med. 2010;72(4):404–11.CrossRefPubMedGoogle Scholar
  52. 52.
    Tracey I. Can neuroimaging studies identify pain endophenotypes in humans? Nat Rev Neurol. 2011;7(3):173–81.CrossRefPubMedGoogle Scholar
  53. 53.
    Valet M, Gündel H, Sprenger T, Sorg C, Mühlau M, Zimmer C, et al. Patients with pain disorder show gray-matter loss in pain-processing structures: a voxel-based morphometric study. Psychosom Med. 2009;71(1):49–56.CrossRefPubMedGoogle Scholar
  54. 54.
    Vogt BA. Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci. 2005;6(7):533–44.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Wiech K, Ploner M, Tracey I. Neurocognitive aspects of pain perception. Trends Cognit Sci. 2008;12(8):306–13.CrossRefGoogle Scholar
  56. 56.
    Yoshino A, Okamoto Y, Horikoshi M, Oshita K, Nakamura R, Otsuru N et al. Effectiveness of group cognitive behavioral therapy (GCBT) for somatoform pain disorder patients in Japan: a preliminary non-case-control study. Psychiatry and clinical neurosciences. 2015; in press.Google Scholar
  57. 57.
    Yoshino A, Okamoto Y, Kunisato Y, Yoshimura S, Jinnin R, Hayashi Y, et al. Distinctive spontaneous regional neural activity in patients with somatoform pain disorder: a preliminary resting-state fMRI study. Psychiatry Res Neuroimaging. 2014;221:246–8.CrossRefPubMedGoogle Scholar
  58. 58.
    Yoshino A, Okamoto Y, Onoda K, Shishida K, Yoshimura S, Kunisato Y, et al. Sadness enhances the experience of pain and affects pain-evoked cortical activities: An MEG study. J Pain. 2012;13:628–35.CrossRefPubMedGoogle Scholar
  59. 59.
    Yoshino A, Okamoto Y, Onoda K, Yoshimura S, Kunisato Y, Demoto Y et al. Sadness enhances the experience of pain via neural activation in the anterior cingulate cortex and amygdala: an fMRI study. Neuroimage. 2010;50:1194–201. doi: 10.1016/j.neuroimage.2009.11.079 S1053-8119(09)01265-8 [pii].
  60. 60.
    Yoshino A, Okamoto Y, Yoshimura S, Shishida K, Toki S, Doi M et al. Distinctive neural responses to pain stimuli during induced sadness in patients with somatoform pain disorder: an fMRI study. Neuroimage: Clinic. 2013;2:782–9.Google Scholar
  61. 61.
    Zhang D, Raichle ME. Disease and the brain’s dark energy. Nat Rev Neurol. 2010;6(1):15–28.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Atsuo Yoshino
    • 1
  • Yasumasa Okamoto
    • 1
  • Shigeto Yamawaki
    • 1
  1. 1.Department of Psychiatry and Neurosciences, Division of Frontier Graduate School of Biomedical SciencesHiroshima UniversityMinami-kuJapan

Personalised recommendations