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Oral and Craniofacial Pain: Contribution of Endogenous, Central Modulation Mechanisms

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Orofacial Pain Biomarkers

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Abstract

In this chapter, we will describe the main endogenous, central modulation and related maladaptive mechanisms involved in processing oral and craniofacial pain. In particular, we will explain how the functional anatomy and pathophysiology of brainstem, hypothalamic, and corticofugal networks may alter the excitability of the trigeminal system. We will describe our recent findings showing a direct anatomo-functional relationship between cortical, hypothalamic excitability disturbances and dysfunctions of medullary trigeminovascular regions. We will analyze the impact of such dysfunctions as putative biomarkers of central sensitization phenomena at the origin of sustained trigeminal pain.

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References

  1. Woda A, Molat JL, Luccarini P. Low doses of N-methyl-d-aspartate antagonists in superficial laminae of medulla oblongata facilitate wind-up of convergent neurones. Neuroscience. 2001;107:317–27.

    Article  PubMed  Google Scholar 

  2. Bereiter DA, Hirata H, Hu JW. Trigeminal subnucleus caudalis: beyond homologies with the spinal dorsal horn. Pain. 2000;88:221–4.

    Article  PubMed  Google Scholar 

  3. Jacquin MF, Chiaia NL, Haring JH, Rhoades RW. Intersubnuclear connections within the rat trigeminal brainstem complex. Somatosens Mot Res. 1990b;7:399–420.

    Article  PubMed  Google Scholar 

  4. DaSilva AF, Becerra L, Makris N, Strassman AM, Gonzalez RG, Geatrakis N, Borsook D. Somatotopic activation in the human trigeminal pain pathway. J Neurosci. 2002;22:8183–92.

    PubMed  Google Scholar 

  5. Jacquin MF, Barcia M, Rhoades RW. Structure-function relationships in rat brainstem subnucleus interpolaris: IV. Projection neurons. J Comp Neurol. 1989;282:45–62.

    Article  PubMed  Google Scholar 

  6. Peschanski M. Trigeminal afferents to the diencephalon in the rat. Neuroscience. 1984;12:465–87.

    Article  PubMed  Google Scholar 

  7. Henry JL, Sessle BJ, Lucier GE, Hu JW. Effects of substance P on nociceptive and non-nociceptive trigeminal brain stem neurons. Pain. 1980;8:33–45.

    Article  PubMed  Google Scholar 

  8. Bereiter DA, Bereiter DF. N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor antagonism reduces Fos-like immunoreactivity in central trigeminal neurons after corneal stimulation in the rat. Neuroscience. 1996;73:249–58.

    Article  PubMed  Google Scholar 

  9. Parada CA, Luccarini P, Woda A. Effect of an NMDA receptor antagonist on the wind-up of neurons in the trigeminal oralis subnucleus. Brain Res. 1997;761:313–20.

    Article  PubMed  Google Scholar 

  10. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971–9.

    Article  PubMed  Google Scholar 

  11. Le Bars D, Dickenson AH, Besson JM, Villanueva L. Aspects of sensory processing through convergent neurons. In: Yaksh TL, editor. Spinal afferent processing. New York: Plenum; 1986. p. 467–504.

    Chapter  Google Scholar 

  12. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139:267–84.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Miraucourt LS, Dallel R, Voisin DL. Glycine inhibitory dysfunction turns touch into pain through PKCgamma interneurons. PLoS One. 2007;2:e1116.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Nakajima A, Tsuboi Y, Suzuki I, Honda K, Shinoda M, Kondo M, et al. PKC{gamma} in Vc and C1/C2 is involved in trigeminal neuropathic pain. J Dent Res. 2011;90:777–81.

    Article  PubMed  Google Scholar 

  15. Woolf CJ, Mitchell D, Barrett GD. Antinociceptive effect of peripheral segmental electrical stimulation in the rat. Pain. 1980;8:237–52.

    Article  PubMed  Google Scholar 

  16. Chung JM, Lee KH, Hori Y, Endo K, Willis WD. Factors influencing peripheral nerve stimulation produced inhibition of primate spinothalamic tract cells. Pain. 1984;19:277–93.

    Article  PubMed  Google Scholar 

  17. Bouhassira D, Le Bars D, Villanueva L. Heterotopic activation of A delta and C fibres triggers inhibition of trigeminal and spinal convergent neurones in the rat. J Physiol. 1987;389:301–17.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Andersson SA. Pain control by sensory stimulation. In: Bonica J, Liebeskind JC, Albe-Fessard D, editors. Advances in pain research and therapy, vol. 3. Seattle: IASP Press; 1979. p. 569–85.

    Google Scholar 

  19. Melzack R. Acupuncture and related forms of folk medicine. In: Wall PD, Melzack R, editors. Texbook of pain. Edinburgh: Churchill Livingstone; 1984. p. 691–701.

    Google Scholar 

  20. Deslile D, Plaghki L. La neurostimulation électrique transcutanée est-elle capable de modifier la perception de la douleur ? Une méta-analyse Douleur et analgésie. 1990;3:115–22.

    Article  Google Scholar 

  21. Chesterton LS, Foster NE, Wright CC, Baxter GD, Barlas P. Effects of TENS frequency, intensity and stimulation site parameter manipulation on pressure pain thresholds in healthy human subjects. Pain. 2003;106:73–80.

    Article  PubMed  Google Scholar 

  22. Le Bars D, Dickenson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain. 1979;6:283–304.

    Article  PubMed  Google Scholar 

  23. Dickenson AH, Le Bars D, Besson JM. Diffuse noxious inhibitory controls (DNIC). Effects on trigeminal nucleus caudalis neurones in the rat. Brain Res. 1980;200:293–305.

    Article  PubMed  Google Scholar 

  24. Villanueva L, Cadden S, Le Bars D. Diffuse Noxious Inhibitory Controls (DNIC) : evidence for post-synaptic inhibition of trigeminal nucleus caudalis convergent neurones. Brain Res. 1984;321:165–8.

    Article  PubMed  Google Scholar 

  25. Villanueva L, Bouhassira D, Bing Z, Le Bars D. Convergence of heterotopic nociceptive information onto subnucleus reticularis dorsalis neurons in the rat medulla. J Neurophysiol. 1988;60:980–1009.

    PubMed  Google Scholar 

  26. Villanueva L, Bouhassira D, Le Bars D. The medullary subnucleus reticularis dorsalis (SRD) as a key link in both the transmission and modulation of pain signals. Pain. 1996;67:231–40.

    Article  PubMed  Google Scholar 

  27. Bouhassira D, Villanueva L, Bing Z, le Bars D. Involvement of the subnucleus reticularis dorsalis in diffuse noxious inhibitory controls in the rat. Brain Res. 1992;595(2):353–7.

    Article  PubMed  Google Scholar 

  28. De Broucker T, Cesaro P, Willer JC, Le Bars D. Diffuse noxious inhibitory controls in man. Involvement of the spinoreticular tract. Brain. 1990;113:1223–34.

    Article  PubMed  Google Scholar 

  29. Le Bars D. The whole body receptive field of dorsal horn multireceptive neurones. Brain Res Rev. 2002;40:29–44.

    Article  PubMed  Google Scholar 

  30. Defrin R, Tsedek I, Lugasi I, Moriles I, Urca G. The interactions between spatial summation and DNIC: effect of the distance between two painful stimuli and attentional factors on pain perception. Pain. 2010;151:489–95.

    Article  PubMed  Google Scholar 

  31. Villanueva L, Fields HL. Endogenous central mechanisms of pain modulation. In: Villanueva L, Dickenson AH, Ollat H, editors. The pain system in normal and pathological states: a primer for clinicians. Progress in pain research and management, vol. 31. Seattle: IASP Press; 2004. p. 223–46.

    Google Scholar 

  32. Roby-Brami A, Bussel B, Willer JC, Le Bars D. An electrophysiological investigation into the pain-relieving effects of heterotopic nociceptive stimuli. Probable involvement of a supraspinal loop. Brain. 1987;110:1497–508.

    Article  PubMed  Google Scholar 

  33. Maillou P, Cadden SW. Effects of remote deep somatic noxious stimuli on a jaw reflex in man. Arch Oral Biol. 1997;42:323–7.

    Article  PubMed  Google Scholar 

  34. Villanueva L, Le Bars D. The activation of bulbo-spinal controls by peripheral nociceptive inputs: diffuse noxious inhibitory controls. Biol Res. 1995;28:113–25.

    PubMed  Google Scholar 

  35. Piché M, Arsenault M, Rainville P. Cerebral and cerebrospinal processes underlying counterirritation analgesia. J Neurosci. 2009;29:14236–46.

    Article  PubMed  Google Scholar 

  36. Sprenger C, Bingel U, Buchel C. Treating pain with pain: supraspinal mechanisms of endogenous analgesia elicited by heterotopic noxious conditioning stimulation. Pain. 2011;152:428–39.

    Article  PubMed  Google Scholar 

  37. Bouhassira D, Danziger N, Attal N, Guirimand F. Comparison of the pain suppressive effects of clinical and experimental painful conditioning stimuli. Brain. 2003;126:1068–78.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  39. King CD, Wong F, Currie T, Mauderli AP, Fillingim RB, Riley 3rd JL. Deficiency in endogenous modulation of prolonged heat pain in patients with Irritable Bowel Syndrome and Temporomandibular Disorder. Pain. 2009;143:172–8.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Leonard G, Goffaux P, Mathieu D, Blanchard J, Kenny B, Marchand S. Evidence of descending inhibition deficits in atypical but not classical trigeminal neuralgia. Pain. 2009;147:217–23.

    Article  PubMed  Google Scholar 

  41. Pielsticker A, Haag G, Zaudig M, Lautenbacher S. Impairment of pain inhibition in chronic tension-type headache. Pain. 2005;118:215–23.

    Article  PubMed  Google Scholar 

  42. Cathcart S, Winefield AH, Lushington K, Rolan P. Noxious inhibition of temporal summation is impaired in chronic tension-type headache. Headache. 2010;50:403–12.

    Article  PubMed  Google Scholar 

  43. Okada-Ogawa A, Porreca F, Meng ID. Sustained morphine-induced sensitization and loss of diffuse noxious inhibitory controls in dura-sensitive medullary dorsal horn neurons. J Neurosci. 2009;29:15828–35.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Oliveras JL, Besson JM. Stimulation-produced analgesia in animals: behavioural investigations. In: Fields HL, Besson JM, editors. Pain modulation, Progress in brain research, vol. 77. Amsterdam/New York: Elsevier; 1988. p. 141–57.

    Google Scholar 

  45. Suzuki R, Morcuende S, Webber M, Hunt SP, Dickenson AH. Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways. Nat Neurosci. 2002;5:1319–26.

    Article  PubMed  Google Scholar 

  46. Craig AD. A new view of pain as a homeostatic emotion. Trends Neurosci. 2003;26:303–7.

    Article  PubMed  Google Scholar 

  47. Lovick TA. The medullary raphe nuclei: a system for integration and gain control in autonomic and somatomotor responsiveness? Exp Physiol. 1997;82:31–41.

    Article  PubMed  Google Scholar 

  48. Mason P. Contributions of the medullary raphe and ventromedial reticular region to pain modulation and other homeostatic functions. Annu Rev Neurosci. 2001;24:737–77.

    Article  PubMed  Google Scholar 

  49. Fields HL, Heinricher MM, Mason P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci. 1991;14:219–45.

    Article  PubMed  Google Scholar 

  50. Leung CG, Mason P. Physiological properties of raphe magnus neurons during sleep and waking. J Neurophysiol. 1999;81:584–95.

    PubMed  Google Scholar 

  51. Oliveras JL, Martin G, Montagne-Clavel J. Drastic changes of ventromedial medulla neuronal properties induced by barbiturate anesthesia. II. Modifications of the single-unit activity produced by Brevital, a short-acting barbiturate in the awake, freely moving rat. Brain Res. 1991;563:251–60.

    Article  PubMed  Google Scholar 

  52. McGaraughty S, Reinis S, Tsoukatos J. Two distinct unit activity responses to morphine in the rostral ventromedial medulla of awake rats. Brain Res. 1993;604:331–3.

    Article  PubMed  Google Scholar 

  53. Rivat C, Becker C, Blugeot A, Zeau B, Mauborgne A, Pohl M, et al. Chronic stress induces transient spinal neuroinflammation, triggering sensory hypersensitivity and long-lasting anxiety-induced hyperalgesia. Pain. 2010;150:358–68.

    Article  PubMed  Google Scholar 

  54. Craig AD, Bushnell MC. The thermal grill illusion: unmasking the burn of cold pain. Science. 1994;265(5169):252–5.

    Article  PubMed  Google Scholar 

  55. 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(4):463–84.

    Article  PubMed  Google Scholar 

  56. Colloca L, Benedetti F. Placebos and painkillers: is mind as real as matter? Nat Rev Neurosci. 2005;6(7):545–52.

    Article  PubMed  Google Scholar 

  57. Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55(3):377–91.

    Article  PubMed  Google Scholar 

  58. Sessle BJ, Hu JW, Dubner R, Lucier GE. Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). II. Modulation of responses to noxious and nonnoxious stimuli by periaqueductal gray, nucleus raphe magnus, cerebral cortex, and afferent influences, and effect of naloxone. J Neurophysiol. 1981;45:193–207.

    PubMed  Google Scholar 

  59. Bushnell MC, Duncan GH, Dubner R, He LF. Activity of trigeminothalamic neurons in medullary dorsal horn of awake monkeys trained in a thermal discrimination task. J Neurophysiol. 1984;52:170–87.

    PubMed  Google Scholar 

  60. Duncan GH, Bushnell MC, Dubner R. Task-related responses of monkey medullary dorsal horn neurons. J Neurophysiol. 1987;57:289–310.

    PubMed  Google Scholar 

  61. Avivi-Arber L, Martin R, Lee JC, Sessle BJ. Face sensorimotor cortex and its neuroplasticity related to orofacial sensorimotor functions. Arch Oral Biol. 2011;56(12):1440–65. doi:10.1016/j.archoralbio.2011.04.005.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  63. Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. Prog Neurobiol. 2009;87:81–97.

    Article  PubMed  Google Scholar 

  64. Deschênes M, Veinante P, Zhang ZW. The organization of corticothalamic projections: reciprocity versus parity. Brain Res Rev. 1998;28:286–308.

    Article  PubMed  Google Scholar 

  65. Rauscheker JP. Cortical control of the thalamus: top-down processing and plasticity. Nat Neurosci. 1998;1:179–80.

    Article  Google Scholar 

  66. Krupa DJ, Ghazanfar AA, Nicolelis MA. Immediate thalamic sensory plasticity depends on corticothalamic feedback. Proc Natl Acad Sci U S A. 1999;96:8200–5.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Monconduit L, Lopez-Avila A, Molat JL, Chalus M, Villanueva L. Corticothalamic feedback selectively modulates innocuous and noxious inputs in the rat spinothalamic system. J Neurosci. 2006;26:8441–50.

    Article  PubMed  Google Scholar 

  68. Nahmias F, Debes C, de Andrade DC, Mhalla A, Bouhassira D. Diffuse analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers. Pain. 2009;147:224–32.

    Article  PubMed  Google Scholar 

  69. Ramachadran VS. Consciousness and body image: lessons from phantom limbs, Capgras syndrome and pain asymbolia. Philos Trans R Soc Lond B Biol Sci. 1998;353:1851–9.

    Article  Google Scholar 

  70. Borsook D, Becerra L, Fishman S, et al. Acute plasticity in the human somatosensory cortex following amputation. Neuroreport. 1998;9:1013–7.

    Article  PubMed  Google Scholar 

  71. Gandevia SC, Phegan CM. Perceptual distortions of the human body image produced by local anaesthesia, pain and cutaneous stimulation. J Physiol. 1999;514:609–16.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Annu Rev Physiol. 2013;75:365–91.

    Article  PubMed  Google Scholar 

  73. 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;98:4687–92.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Coppola G, Pierelli F, Schoenen J. Is the cerebral cortex hyperexcitable or hyperresponsive in migraine? Cephalalgia. 2007;27:1427–39.

    Article  PubMed  Google Scholar 

  75. Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med. 2002;8:136–42.

    Article  PubMed  Google Scholar 

  76. Burstein R, Strassman A, Moskowitz M. Can cortical spreading depression activate central trigeminovascular neurons without peripheral input? Pitfalls of a new concept. Cephalalgia. 2012;32(6):509–11.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Noseda R, Constandil L, Bourgeais L, Chalus M, Villanueva L. Changes of meningeal excitability mediated by corticotrigeminal networks: a link for the endogenous modulation of migraine pain. J Neurosci. 2010;30:14420–9.

    Article  PubMed  Google Scholar 

  78. Theriot JJ, Toga AW, Prakash N, Ju YS, Brennan KC. Cortical sensory plasticity in a model of migraine with aura. J Neurosci. 2012;32(44):15252–61.

    Article  PubMed  PubMed Central  Google Scholar 

  79. May A. New insights into headache: an update on functional and structural imaging findings. Nat Rev Neurol. 2009;5:199–209.

    Article  PubMed  Google Scholar 

  80. Leone M, Franzini A, Bussone G. Stereotactic stimulation of posterior hypothalamic gray matter in a patient with intractable cluster headache. N Engl J Med. 2001;345(19):1428–9.

    Article  PubMed  Google Scholar 

  81. Robert C, Bourgeais L, Arreto CD, Condes-Lara M, Noseda R, Jay T, et al. Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches. J Neurosci. 2013;33(20):8827–40.

    Article  PubMed  Google Scholar 

  82. Akerman S, Holland PR, Summ O, Lasalandra MP, Goadsby PJ. A translational in vivo model of trigeminal autonomic cephalalgias: therapeutic characterization. Brain. 2012;135:3664–75.

    Article  PubMed  Google Scholar 

  83. Simmons DM, Swanson LW. Comparison of the spatial distribution of seven types of neuroendocrine neurons in the rat paraventricular nucleus: toward a global 3D model. J Comp Neurol. 2009;516:423–41.

    Article  PubMed  Google Scholar 

  84. Swanson LW, Sawchenko PE. Paraventricular nucleus: a site for the integration of neuroendocrine and autonomic mechanisms. Neuroendocrinology. 1980;31:410–7.

    Article  PubMed  Google Scholar 

  85. Hewitt SA, Wamsteeker JI, Kurz EU, Bains JS. Altered chloride homeostasis removes synaptic inhibitory constraint of the stress axis. Nat Neurosci. 2009;12:438–43.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors are very grateful to Pr. Yves Boucher for his valuable advice in the preparation of this manuscript. This work was supported by INSERM, Université Paris Descartes, Institut UPSA de la Douleur, and Association Gliaxone.

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Authors and Affiliations

  1. INSERM / Université Paris Descartes - UFR des Sciences Fondamentales et Biomédicales, UMR 894, Centre de Psychiatrie et Neurosciences, Paris, France

    Laurence Bourgeais Rambur PhD

  2. INSERM / Université Paris Descartes - Faculté de Chirurgie Dentaire, UMR 894, Centre de Psychiatrie et Neurosciences, Paris, France

    Charles-Daniel Arreto DDS, PhD & Claude Robert PhD

  3. INSERM, UMR 894, Centre de Psychiatrie et Neurosciences, Paris, France

    Luis Villanueva DDS, PhD

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  1. Laurence Bourgeais Rambur PhD
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  4. Luis Villanueva DDS, PhD
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Correspondence to Laurence Bourgeais Rambur PhD .

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Editors and Affiliations

  1. Faculté de médecine dentaire, Université Laval, Québec, Canada

    Jean-Paul Goulet

  2. Faculty of Dentistry, McGill University, Department of Dentistry of Jewish General Hospital, Montréal, Québec, Canada

    Ana Miriam Velly

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Rambur, L.B., Arreto, CD., Robert, C., Villanueva, L. (2017). Oral and Craniofacial Pain: Contribution of Endogenous, Central Modulation Mechanisms. In: Goulet, JP., Velly, A. (eds) Orofacial Pain Biomarkers. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-53994-1_4

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