Advertisement

Mechanisms of Pain and Headache

  • Alexandre F. M. DaSilvaEmail author
  • Marcos Fabio DosSantos
Chapter
Part of the Headache book series (HEAD)

Abstract

Recent years have witnessed great advances in the neuroimaging field that permitted the elaborated evaluation of the brain structure and, most importantly, the complex central activity that takes place in humans at rest and during different types of functional challenges or cognitive activities. Such functional and structural studies provided fundamental information that when correlated with clinical symptoms brought better understanding for the cortical and subcortical mechanisms related to chronic pain syndromes. With regard to primary headaches, most of the MRI-based neuroimaging studies explored the pathophysiology of migraine and its related signs and symptoms such as pain severity, nausea, phonophobia, photophobia, and allodynia. Considering the unique cyclic characteristic of the disease, migraine research offers additional opportunities and logistic challenges including the study of patients during and outside their attacks (ictal and interictal phases, respectively), the increased sensitive to stimuli from the environment, and response to treatment. More recent studies using positron-emission tomography (PET) have provided novel clues at molecular level of major endogenous modulatory systems that could play an important role in the development and maintenance of migraine and other chronic pain states. For instance, molecular neuroimaging has showed in vivo that there is a significant dysfunction in endogenous mu-opioidergic and dopaminergic mechanisms during migraine attacks and allodynia, as well as neuropathic pain. In this chapter, we discuss novel discoveries using neuroimaging, including the role of central molecular mechanisms in migraine/pain suffering and treatment.

Keywords

Chronic pain Migraine Fibromyalgia Neuroimaging Neuroplasticity Mu-opioid receptors Functional magnetic resonance imaging Positron-emission tomography 

References

  1. 1.
    Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ, Frackowiak RS, et al. A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Brain. 2005;128.(Pt 4:932–9.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Aimone LD, Jones SL, Gebhart GF. Stimulation-produced descending inhibition from the periaqueductal gray and nucleus raphe magnus in the rat: mediation by spinal monoamines but not opioids. Pain. 1987;31(1):123–36.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Apkarian AV, Sosa Y, Sonty S, Levy RM, Harden RN, Parrish TB, et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004;24(46):10410–5.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Baliki MN, Geha PY, Fields HL, Apkarian AV. Predicting value of pain and analgesia: nucleus accumbens response to noxious stimuli changes in the presence of chronic pain. Neuron. 2010;66(1):149–60.PubMedPubMedCentralCrossRefGoogle 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.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–84.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Benatto MT, Florencio LL, Carvalho GF, Dach F, Bigal ME, Chaves TC, et al. Cutaneous allodynia is more frequent in chronic migraine, and its presence and severity seems to be more associated with the duration of the disease. Arq Neuropsiquiatr. 2017;75(3):153–9.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Bigal ME, Ashina S, Burstein R, Reed ML, Buse D, Serrano D, et al. Prevalence and characteristics of allodynia in headache sufferers: a population study. Neurology. 2008;70(17):1525–33.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006;10(4):287–333.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Burstein R. Deconstructing migraine headache into peripheral and central sensitization. Pain. 2001;89(2–3):107–10.PubMedCrossRefGoogle Scholar
  11. 11.
    Burstein R, Cutrer MF, Yarnitsky D. The development of cutaneous allodynia during a migraine attack clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain. 2000;123(Pt 8):1703–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH. An association between migraine and cutaneous allodynia. Ann Neurol. 2000;47(5):614–24.PubMedCrossRefGoogle Scholar
  13. 13.
    Cao Y, Aurora SK, Nagesh V, Patel SC, Welch KM. Functional MRI-BOLD of brainstem structures during visually triggered migraine. Neurology. 2002;59(1):72–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Chen Z, Chen X, Liu M, Dong Z, Ma L, Yu S. Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis. J Headache Pain. 2017;18(1):7.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Chong CD, Dodick DW, Schlaggar BL, Schwedt TJ. Atypical age-related cortical thinning in episodic migraine. Cephalalgia. 2014;34(14):1115–24.PubMedCrossRefGoogle Scholar
  16. 16.
    Chong CD, Schwedt TJ, Dodick DW. Migraine: what imaging reveals. Curr Neurol Neurosci Rep. 2016;16(7):64.PubMedCrossRefGoogle Scholar
  17. 17.
    Chong CD, Schwedt TJ, Hougaard A. Brain functional connectivity in headache disorders: a narrative review of MRI investigations. J Cereb Blood Flow Metab. 2017:271678X17740794.Google Scholar
  18. 18.
    Coppola G, Di Renzo A, Tinelli E, Di Lorenzo C, Di Lorenzo G, Parisi V, et al. Thalamo-cortical network activity during spontaneous migraine attacks. Neurology. 2016;87(20):2154–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Coppola G, Di Renzo A, Tinelli E, Di Lorenzo C, Scapeccia M, Parisi V, et al. Resting state connectivity between default mode network and insula encodes acute migraine headache. Cephalalgia 2017:333102417715230.Google Scholar
  20. 20.
    DaSilva AF, Granziera C, Snyder J, Hadjikhani N. Thickening in the somatosensory cortex of patients with migraine. Neurology. 2007;69(21):1990–5.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    DaSilva A, Granziera C, Snyder J, Hadjikhani N. Thickening in the somatosensory cortex of patients with migraine. Neurology. 2007;69(21):1990–5.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    DaSilva A, Granziera C, Tuch D, Snyder J, Vincent M, Hadjikhani N. Interictal alterations of the trigeminal somatosensory pathway and periaqueductal gray matter in migraine. Neuroreport. 2007;18(4):301–5.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    DaSilva AF, Becerra L, Pendse G, Chizh B, Tully S, Borsook D. Colocalized structural and functional changes in the cortex of patients with trigeminal neuropathic pain. PLoS One. 2008;3(10):e3396.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    DaSilva AF, Nascimento TD, Love T, DosSantos MF, Martikainen IK, Cummiford CM, et al. 3D-neuronavigation in vivo through a patient’s brain during a spontaneous migraine headache. J Vis Exp. 2014;(88).Google Scholar
  25. 25.
    DaSilva AF, Nascimento TD, DosSantos MF, Lucas S, van HolsbeecK H, DeBoer M, et al. Association of μ-opioid activation in the prefrontal cortex with spontaneous migraine attacks—brief report I. Ann Clin Transl Neurol. 2014;1(6):439–44.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    DaSilva AF, Nascimento TD, Jassar H, Heffernan J, Toback RL, Lucas S, et al. Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo. Neurology. 2017;88(17):1634–41.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Datta R, Detre JA, Aguirre GK, Cucchiara B. Absence of changes in cortical thickness in patients with migraine. Cephalalgia. 2011;31(14):1452–8.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Demarquay G, Royet JP, Giraud P, Chazot G, Valade D, Ryvlin P. Rating of olfactory judgements in migraine patients. Cephalalgia. 2006;26(9):1123–30.PubMedCrossRefGoogle Scholar
  29. 29.
    Demarquay G, Lothe A, Royet JP, Costes N, Mick G, Mauguière F, et al. Brainstem changes in 5-HT1A receptor availability during migraine attack. Cephalalgia. 2011;31(1):84–94.PubMedCrossRefGoogle Scholar
  30. 30.
    Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G. Hypothalamic activation in spontaneous migraine attacks. Headache. 2007;47(10):1418–26.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Dodick D, Silberstein S. Central sensitization theory of migraine: clinical implications. Headache. 2006;46(Suppl 4):S182–91.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Dogrul A, Seyrek M, Yalcin B, Ulugol A. Involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception. Prog Neuro-Psychopharmacol Biol Psychiatry. 2012;38(1):97–105.CrossRefGoogle Scholar
  33. 33.
    Dossantos MF, Martikainen IK, Nascimento TD, Love TM, Deboer MD, Maslowski EC, et al. Reduced basal ganglia mu-opioid receptor availability in trigeminal neuropathic pain: a pilot study. Mol Pain. 2012;8(1):74.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Dworkin RH, Jensen MP, Gammaitoni AR, Olaleye DO, Galer BS. Symptom profiles differ in patients with neuropathic versus non-neuropathic pain. J Pain. 2007;8(2):118–26.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Elliott AM, Smith BH, Penny KI, Smith WC, Chambers WA. The epidemiology of chronic pain in the community. Lancet. 1999;354(9186):1248–52.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Elliott AM, Smith BH, Hannaford PC, Smith WC, Chambers WA. The course of chronic pain in the community: results of a 4-year follow-up study. Pain. 2002;99(1–2):299–307.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Fishman S, Ballantyne J, Rathmell JP, Bonica JJ. Bonica’s management of pain. Philadelphia: Lippincott, Williams & Wilkins; 2010.Google Scholar
  38. 38.
    Granziera C, DaSilva AF, Snyder J, Tuch DS, Hadjikhani N. Anatomical alterations of the visual motion processing network in migraine with and without aura. PLoS Med. 2006;3(10):e402.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A. 2001;98(8):4687–92.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Hadjikhani N, Ward N, Boshyan J, Napadow V, Maeda Y, Truini A, et al. The missing link: enhanced functional connectivity between amygdala and visceroceptive cortex in migraine. Cephalalgia. 2013;33(15):1264–8.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Hagelberg N, Forssell H, Aalto S, Rinne JO, Scheinin H, Taiminen T, et al. Altered dopamine D2 receptor binding in atypical facial pain. Pain. 2003;106(1–2):43–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Hagelberg N, Forssell H, Rinne JO, Scheinin H, Taiminen T, Aalto S, et al. Striatal dopamine D1 and D2 receptors in burning mouth syndrome. Pain. 2003;101(1–2):149–54.PubMedCrossRefGoogle Scholar
  43. 43.
    Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007;27(37):10000–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629–808.CrossRefGoogle Scholar
  45. 45.
    von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012;73(4):638–52.CrossRefGoogle Scholar
  46. 46.
    Heinricher MM, Tavares I, Leith JL, Lumb BM. Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev. 2009;60(1):214–25.PubMedCrossRefGoogle Scholar
  47. 47.
    Jensen MP, Dworkin RH, Gammaitoni AR, Olaleye DO, Oleka N, Galer BS. Assessment of pain quality in chronic neuropathic and nociceptive pain clinical trials with the Neuropathic Pain Scale. J Pain. 2005;6(2):98–106.PubMedCrossRefGoogle Scholar
  48. 48.
    Jones AK, Cunningham VJ, Ha-Kawa S, Fujiwara T, Luthra SK, Silva S, et al. Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis. Br J Rheumatol. 1994;33(10):909–16.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Kim J, Suh S, Seol H, Oh K, Seo W, Yu S, et al. Regional grey matter changes in patients with migraine: a voxel-based morphometry study. Cephalalgia. 2008;28(6):598–604.PubMedCrossRefGoogle Scholar
  50. 50.
    Kröger IL, May A. Triptan-induced disruption of trigemino-cortical connectivity. Neurology. 2015;84(21):2124–31.PubMedCrossRefGoogle Scholar
  51. 51.
    Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343–9.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Lipton RB, Bigal ME, Ashina S, Burstein R, Silberstein S, Reed ML, et al. Cutaneous allodynia in the migraine population. Ann Neurol. 2008;63(2):148–58.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Lothe A, Merlet I, Demarquay G, Costes N, Ryvlin P, Mauguière F. Interictal brain 5-HT1A receptors binding in migraine without aura: a 18F-MPPF-PET study. Cephalalgia. 2008;28(12):1282–91.PubMedCrossRefGoogle Scholar
  54. 54.
    Lovati C, D’Amico D, Bertora P. Allodynia in migraine: frequent random association or unavoidable consequence? Expert Rev Neurother. 2009;9(3):395–408.PubMedCrossRefGoogle Scholar
  55. 55.
    Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol. 2011;70(5):838–45.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Maleki N, Becerra L, Nutile L, Pendse G, Brawn J, Bigal M, et al. Migraine attacks the Basal Ganglia. Mol Pain. 2011;7:71.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Martikainen IK, Nuechterlein EB, Peciña M, Love TM, Cummiford CM, Green CR, et al. Chronic back pain is associated with alterations in dopamine neurotransmission in the ventral striatum. J Neurosci. 2015;35(27):9957–65.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Mason P. Ventromedial medulla: pain modulation and beyond. J Comp Neurol. 2005;493(1):2–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Matharu MS, Cohen AS, McGonigle DJ, Ward N, Frackowiak RS, Goadsby PJ. Posterior hypothalamic and brainstem activation in hemicrania continua. Headache. 2004;44(8):747–61.PubMedCrossRefGoogle Scholar
  60. 60.
    May A. New insights into headache: an update on functional and structural imaging findings. Nat Rev Neurol. 2009;5(4):199–209.PubMedCrossRefGoogle Scholar
  61. 61.
    May A. Understanding migraine as a cycling brain syndrome: reviewing the evidence from functional imaging. Neurol Sci. 2017;38(Suppl 1):125–30.PubMedCrossRefGoogle Scholar
  62. 62.
    May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ. Hypothalamic activation in cluster headache attacks. Lancet. 1998;352(9124):275–8.PubMedCrossRefGoogle Scholar
  63. 63.
    May A, Bahra A, Büchel C, Turner R, Goadsby PJ. Functional magnetic resonance imaging in spontaneous attacks of SUNCT: short-lasting neuralgiform headache with conjunctival injection and tearing. Ann Neurol. 1999;46(5):791–4.PubMedCrossRefGoogle Scholar
  64. 64.
    McMahon SB. Wall and Melzack’s textbook of pain. 6th ed. Philadelphia, PA: Elsevier/Saunders; 2013. xxix, 1153 p.Google Scholar
  65. 65.
    Melzack R, Casey KL. In: Kenshalo D, editor.. The skin senses Sensory, motivational, and central control determinants of pain: a new conceptual model. Springfield, IL: Charles C Thomas; 1968. p. 423–39.Google Scholar
  66. 66.
    Merskey H, Bogduk N, International Association for the Study of Pain. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. Seattle: IASP Press; 1994. xvi, 222 p.Google Scholar
  67. 67.
    Moulton EA, Burstein R, Tully S, Hargreaves R, Becerra L, Borsook D. Interictal dysfunction of a brainstem descending modulatory center in migraine patients. PLoS One. 2008;3(11):e3799.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Nascimento TD, DosSantos MF, Lucas S, van Holsbeeck H, DeBoer M, Maslowski E, et al. μ-Opioid activation in the midbrain during migraine allodynia - brief report II. Ann Clin Transl Neurol. 2014;1(6):445–50.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Niddam DM, Lai KL, Fuh JL, Chuang CY, Chen WT, Wang SJ. Reduced functional connectivity between salience and visual networks in migraine with aura. Cephalalgia. 2016;36(1):53–66.PubMedCrossRefGoogle Scholar
  70. 70.
    Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care. 2014;8(2):143–51.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Qiu E, Wang Y, Ma L, Tian L, Liu R, Dong Z, et al. Abnormal brain functional connectivity of the hypothalamus in cluster headaches. PLoS One. 2013;8(2):e57896.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Sarchielli P, Tarducci R, Presciutti O, Gobbi G, Pelliccioli GP, Stipa G, et al. Functional 1H-MRS findings in migraine patients with and without aura assessed interictally. NeuroImage. 2005;24(4):1025–31.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Schrepf A, Harper DE, Harte SE, Wang H, Ichesco E, Hampson JP, et al. Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study. Pain. 2016;157(10):2217–25.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Schulte LH, May A. Functional neuroimaging in migraine: chances and challenges. Headache. 2016;56(9):1474–81.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Schulte LH, May A. The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain. 2016;139.(Pt 7:1987–93.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Schulte LH, Allers A, May A. Hypothalamus as a mediator of chronic migraine: evidence from high-resolution fMRI. Neurology. 2017;88(21):2011–6.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Schwenkreis P, Scherens A, Rönnau AK, Höffken O, Tegenthoff M, Maier C. Cortical disinhibition occurs in chronic neuropathic, but not in chronic nociceptive pain. BMC Neurosci. 2010;11:73.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Sprenger T, Boecker H, Tolle TR, Bussone G, May A, Leone M. Specific hypothalamic activation during a spontaneous cluster headache attack. Neurology. 2004;62(3):516–7.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Sprenger T, Valet M, Platzer S, Pfaffenrath V, Steude U, Tolle TR. SUNCT: bilateral hypothalamic activation during headache attacks and resolving of symptoms after trigeminal decompression. Pain. 2005;113(3):422–6.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Stankewitz A, May A. Increased limbic and brainstem activity during migraine attacks following olfactory stimulation. Neurology. 2011;77(5):476–82.PubMedCrossRefGoogle Scholar
  81. 81.
    Stankewitz A, Aderjan D, Eippert F, May A. Trigeminal nociceptive transmission in migraineurs predicts migraine attacks. J Neurosci. 2011;31(6):1937–43.PubMedCrossRefGoogle Scholar
  82. 82.
    Steiner TJ, Stovner LJ, Katsarava Z, Lainez JM, Lampl C, Lantéri-Minet M, et al. The impact of headache in Europe: principal results of the Eurolight project. J Headache Pain. 2014;15:31.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Steiner TJ, Birbeck GL, Jensen RH, Katsarava Z, Stovner LJ, Martelletti P. Headache disorders are third cause of disability worldwide. J Headache Pain. 2015;16:58.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Stovner L, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27(3):193–210.PubMedCrossRefGoogle Scholar
  85. 85.
    Tedeschi G, Russo A, Conte F, Corbo D, Caiazzo G, Giordano A, et al. Increased interictal visual network connectivity in patients with migraine with aura. Cephalalgia. 2016;36(2):139–47.PubMedCrossRefGoogle Scholar
  86. 86.
    Vachon-Presseau E, Tétreault P, Petre B, Huang L, Berger SE, Torbey S, et al. Corticolimbic anatomical characteristics predetermine risk for chronic pain. Brain. 2016;139(Pt 7):1958–70.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Verhaak PF, Kerssens JJ, Dekker J, Sorbi MJ, Bensing JM. Prevalence of chronic benign pain disorder among adults: a review of the literature. Pain. 1998;77(3):231–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Weiller C, May A, Limmroth V, Jüptner M, Kaube H, Schayck RV, et al. Brain stem activation in spontaneous human migraine attacks. Nat Med. 1995;1(7):658–60.PubMedCrossRefGoogle Scholar
  89. 89.
    Willoch F, Schindler F, Wester HJ, Empl M, Straube A, Schwaiger M, et al. Central poststroke pain and reduced opioid receptor binding within pain processing circuitries: a [11C]diprenorphine PET study. Pain. 2004;108(3):213–20.PubMedCrossRefGoogle Scholar
  90. 90.
    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(12):3576–82.PubMedCrossRefGoogle Scholar
  91. 91.
    Xue T, Yuan K, Zhao L, Yu D, Dong T, Cheng P, et al. Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI. PLoS One. 2012;7(12):e52927.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Yang FC, Chou KH, Fuh JL, Lee PL, Lirng JF, Lin YY, et al. Altered hypothalamic functional connectivity in cluster headache: a longitudinal resting-state functional MRI study. J Neurol Neurosurg Psychiatry. 2015;86(4):437–45.PubMedCrossRefGoogle Scholar
  93. 93.
    Zhang J, Su J, Wang M, Zhao Y, Yao Q, Zhang Q, et al. Increased default mode network connectivity and increased regional homogeneity in migraineurs without aura. J Headache Pain. 2016;17(1):98.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Zubieta JK. Pain signal as threat and reward. Neuron. 2010;66(1):6–7.PubMedCrossRefGoogle Scholar
  95. 95.
    Zubieta J, Smith Y, Bueller J, Xu Y, Kilbourn M, Jewett D, et al. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science. 2001;293(5528):311–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Alexandre F. M. DaSilva
    • 1
    • 2
    Email author
  • Marcos Fabio DosSantos
    • 1
    • 3
  1. 1.Headache and Orofacial Pain Effort (H.O.P.E.), Department of Biologic and Materials Sciences, School of Dentistry, The Molecular and Behavioral Neuroscience Institute (MBNI)University of MichiganAnn ArborUSA
  2. 2.Center for Human Growth and DevelopmentUniversity of MichiganAnn ArborUSA
  3. 3.Laboratório de Morfogênese Celular (LMC), Instituto de Ciências Biomédicas (ICB)Universidade Federal do Rio de Janeiro (UFRJ)Rio de JaneiroBrazil

Personalised recommendations