Current Pain and Headache Reports

, Volume 7, Issue 5, pp 371–376 | Cite as

The trigeminocervical complex and migraine: Current concepts and synthesis

  • T. Bartsch
  • Peter J. Goadsby
Article

Abstract

Neurones in the trigeminocervical complex are the major relay neurones for nociceptive afferent input from the meninges and cervical structures; therefore, they are the neural substrates of head pain. This review highlights the importance of two basic mechanisms in headache physiology: convergence of nociceptive afferents and sensitization of trigeminocervical neurones. These physiologic findings have clinical correlates such as hypersensitivity and spread and referral of pain frequently seen in patients with primary headache, such as migraine. Special reference is made to the influence of structures from the upper cervical spine in generating and contributing to migraine headaches. The pathophysiology and functional relevance of these basic mechanisms to headaches is discussed in the context of recent experimental findings with regard to pain processing.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Goadsby PJ, Lipton RB, Ferrari MD: Migraine: current understanding and treatment. N Engl J Med 2002, 346:257–227.PubMedCrossRefGoogle Scholar
  2. 2.
    Anthony M: Headache and the greater occipital nerve. Clin Neurol Neurosurg 1992, 94:297–301.PubMedCrossRefGoogle Scholar
  3. 3.
    Bogduk N. Headache and the neck. In Headache. Edited by Goadsby PJ, Silberstein SD. Oxford: Butterworth Heinemann; 1997:369–381 (Edited by Asbury AK, Marsden CD. Blue Books in Practical Neurology, vol 17).Google Scholar
  4. 4.
    Selby G, Lance JW: Observations on 500 cases of migraine and allied vascular headache. J Neurol Neurosurg Psychiatry 1960, 23:23–32.PubMedGoogle Scholar
  5. 5.
    Kerr FW: A mechanism to account for frontal headache in cases of posterior fossa tumous. J Neurosurg 1961, 18:60.Google Scholar
  6. 6.
    Wolff HG: Headache and Other Head Pain, edn 1. New York: Oxford University Press; 1948.Google Scholar
  7. 7.
    Hunter CR, Mayfield FH: Role of the upper cervical roots in the production of pain in the head. Am J Surg 1949, 78:743–749.PubMedCrossRefGoogle Scholar
  8. 8.
    Cremer P, Halmagyi GM, Goadsby PJ: Secondary cluster headache responsive to sumatriptan. J Neurol Neurosurg Psychiatry 1995, 59:633–634.PubMedGoogle Scholar
  9. 9.
    Hutchinson PJ, Pickard JD, Higgins JN: Vertebral artery dissection presenting as cerebellar infarction. J Neurol Neurosurg Psychiatry 2000, 68:98–99.PubMedCrossRefGoogle Scholar
  10. 10.
    Piovesan EJ, Kowacs PA, Tatsui CE, et al.: Referred pain after painful stimulation of the greater occipital nerve in humans: evidence of convergence of cervical afferents on trigeminal nuclei. Cephalalgia 2001, 21:107–109.PubMedCrossRefGoogle Scholar
  11. 11.
    Feinstein B, Langton JN, Jameson RM, Schiller F: Experiments on pain referred from deep somatic tissues. J Bone Joint Surg 1954, 36A:981–997.Google Scholar
  12. 12.
    Wirth FP, van Buren JM: Referral of pain from dural stimulation in man. J Neurosurg 1971, 34:630–642.PubMedCrossRefGoogle Scholar
  13. 13.
    Ruch TC: Pathophysiology of pain. In Physiology and Biophysics. Edited by Ruch TC, Patton HD. Philadelphia: WB Saunders; 1965:345–363.Google Scholar
  14. 14.
    Mackenzie J: Symptoms and Their Interpretation. London: Shaw and Sons; 1909.Google Scholar
  15. 15.
    Strassman AM, Raymond SA, Burstein R: Sensitization of meningeal sensory neurons and the origin of headaches. Nature 1996, 384:560–563.PubMedCrossRefGoogle Scholar
  16. 16.
    Burstein R, Cutrer MF, Yarnitsky D: The development of cutaneous allodynia during a migraine attack. Brain 2000, 123:1703–1709. A study showing that the features of a central sensitization of the nociceptive system are present during a migraine attack.PubMedCrossRefGoogle Scholar
  17. 17.
    Ray BS, Wolff HG: Experimental studies on headache: pain sensitive structures of the head and their significance in headache. Arch Surg 1940, 41:813–856.Google Scholar
  18. 18.
    Penfield W, McNaughton FL: Dural headache and the innervation of the dura mater. Arch Neurol Psychiatry 1940, 44:43–75.Google Scholar
  19. 19.
    Burstein R, Yamamura H, Malick A, Strassman AM: Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J Neurophysiol 1998, 79:964–982.PubMedGoogle Scholar
  20. 20.
    Schepelmann K, Ebersberger A, Pawlak M, et al.: Response properties of trigeminal brain stem neurons with input from dura mater encephali in the rat. Neuroscience 1999, 90:543–554.PubMedCrossRefGoogle Scholar
  21. 21.
    Bartsch T, Goadsby PJ: Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input. Brain 2002, 125:1496–1509. An electrophysiologic study describing the convergence of dural afferents and cervical afferents in the GON on to neurons in the trigeminocervical complex with subsequent sensitization of dural input by stimulation of the GON. The study describes a model of how common clinical features in patients with headache, such as hypersensitivity, spread, and referral from structures of the upper cervical spine in the trigeminal domain can be attributed to basic neuronal mechanisms in the trigeminocervical complex.PubMedCrossRefGoogle Scholar
  22. 22.
    Levy D, Strassman A: Mechanical response properties of A and C primary afferent neurons innervating the rat intracranial dura. J Neurophysiol 2002, 88:3021–3031. A study that describes a detailed and thorough analysis of the mechanosensitive innervation of the dura mater using electrophysiologic methods.PubMedCrossRefGoogle Scholar
  23. 23.
    Strassman AM, Mineta Y, Vos BP: Distribution of fos-like immunoreactivity in the medullary and upper cervical dorsal horn produced by stimulation of dural blood vessels in the rat. J Neurosci 1994, 14:3725–3735.PubMedGoogle Scholar
  24. 24.
    Kaube H, Keay KA, Hoskin KL, et al.: Expression of c-Fos-like immunoreactivity in the caudal medulla and upper cervical cord following stimulation of the superior sagittal sinus in the cat. Brain Res 1993, 629:95–102.PubMedCrossRefGoogle Scholar
  25. 25.
    Goadsby PJ, Hoskin KL: The distribution of trigeminovascular afferents in the non-human primate brain Macaca nemestrina: a c-fos immunocytochemical study. J Anat 1997, 190:367–337.PubMedCrossRefGoogle Scholar
  26. 26.
    Bogduk N: Cervicogenic headache: anatomic basis and pathophysiologic mechanisms. Curr Pain Headache Rep 2001, 5:382–386. A critical review outlining the anatomy of the cervical spine with regard to strict diagnostic criteria of cervicogenic headache.PubMedCrossRefGoogle Scholar
  27. 27.
    Bogduk N, Aprill C: On the nature of neck pain, discography and cervical zygapophysial joint blocks. Pain 1993, 54:213–217.PubMedCrossRefGoogle Scholar
  28. 28.
    Bakker DA, Richmond FJ, Abrahams VC: Central projections from cat suboccipital muscles: a study using transganglionic transport of horseradish peroxidase. J Comp Neurol 1984, 228:409–421.PubMedCrossRefGoogle Scholar
  29. 29.
    Neuhuber WL, Zenker W: Central distribution of cervical primary afferents in the rat, with emphasis on proprioceptive projections to vestibular, perihypoglossal, and upper thoracic spinal nuclei. J Comp Neurol 1989, 280:231–253.PubMedCrossRefGoogle Scholar
  30. 30.
    Pfister J, Zenker W: The splenius capitis muscle of the rat, architecture and histochemistry, afferent and efferent innervation as compared with that of the quadriceps muscle. Anat Embryol (Berl) 1984, 169:79–89.CrossRefGoogle Scholar
  31. 31.
    Scheurer S, Gottschall J, Groh V: Afferent projections of the rat major occipital nerve studied by transganglionic transport of HRP. Anat Embryol (Berl) 1983, 1983:425–438.CrossRefGoogle Scholar
  32. 32.
    Goadsby PJ, Hoskin KL, Knight YE: Stimulation of the greater occipital nerve increases metabolic activity in the trigeminal nucleus caudalis and cervical dorsal horn of the cat. Pain 1997, 73:23–28.PubMedCrossRefGoogle Scholar
  33. 33.
    Vital JM, Grenier F, Dautheribes M, et al.: An anatomic and dynamic study of the greater occipital nerve (n. of Arnold): applications to the treatment of Arnold’s neuralgia. Surg Radiol Anat 1989, 11:205–210.PubMedCrossRefGoogle Scholar
  34. 34.
    Becser N, Bovim G, Sjaastad O: Extracranial nerves in the posterior part of the head: anatomic variations and their possible clinical significance. Spine 1998, 23:1435–1441.PubMedCrossRefGoogle Scholar
  35. 35.
    Bovim G, Bonamico L, Fredriksen TA, et al.: Topographical variations in the peripheral course of the greater occipital nerve: autopsy study with clinical correlations. Spine 1991, 16:475–478.PubMedCrossRefGoogle Scholar
  36. 36.
    Kerr FW, Olafson RA: Trigeminal and cervical volleys. Arch Neurol 1961, 5:69–76.Google Scholar
  37. 37.
    Jacquin MF, Semba K, Rhoades RW, Egger MD: Trigeminal primary afferents project bilaterally to dorsal horn and ipsilaterally to cerebellum, reticular formation, and cuneate, solitary, supratrigeminal and vagal nuclei. Brain Res 1982, 246:285–291.PubMedCrossRefGoogle Scholar
  38. 38.
    Pfaller K, Arvidsson J: Central distribution of trigeminal and upper cervical primary afferents in the rat studied by anterograde transport of horseradish peroxidase conjugated to wheat germ agglutinin. J Comp Neurol 1988, 268:91–108.PubMedCrossRefGoogle Scholar
  39. 39.
    Ellrich J, Messlinger K: Afferent input to the medullary dorsal horn from the contralateral face in rat. Brain Res 1999, 826:321–324.PubMedCrossRefGoogle Scholar
  40. 40.
    Cervero F, Lumb BM: Bilateral inputs and supraspinal control of viscerosomatic neurons in the lower thoracic spinal cord of the cat. J Physiol 1988, 403:221–237.PubMedGoogle Scholar
  41. 41.
    Linderoth B, Brodin E: ‘Mirror pain’ and indications of bilateral dorsal horn activation in response to unilateral nociception. Pain 1994, 58:277–288.PubMedCrossRefGoogle Scholar
  42. 42.
    Cervero F: Fine afferent fibres from viscera and visceral pain: anatomy and physiology of viscero-somatic convergence. In Fine Afferent Nerve Fibres and Pain. Edited by Schmidt RF, Schaible HG, Vahle-Hinz C. Weinheim, Germany: VCH; 1987:321–333.Google Scholar
  43. 43.
    Cervero F, Laird JM: Visceral pain. Lancet 1999, 353:2145–2148.PubMedCrossRefGoogle Scholar
  44. 44.
    Herrero JF, Laird JM, Lopez-Garcia JA: Wind-up of spinal cord neurons and pain sensation: much ado about something? Prog Neurobiol 2000, 61:169–203.PubMedCrossRefGoogle Scholar
  45. 45.
    Schaible HG, Grubb BD: Afferent and spinal mechanisms of joint pain. Pain 1993, 55:45–54.CrossRefGoogle Scholar
  46. 46.
    Mense S: Nociception from skeletal muscle in relation to clinical muscle pain. Pain 1993, 54:241–289.PubMedCrossRefGoogle Scholar
  47. 47.
    McMahon SB, Lewin GR, Wall PD: Central hyperexcitability triggered by noxious inputs. Curr Opin Neurobiol 1993, 3:602–610.PubMedCrossRefGoogle Scholar
  48. 48.
    Woolf CJ, Salter MW: Neuronal plasticity: increasing the gain in pain. Science 2000, 288:1765–1769.PubMedCrossRefGoogle Scholar
  49. 49.
    Koltzenburg M: Neural mechanisms of cutaneous nociceptive pain. Clin J Pain 2000, 16:S131-S138.PubMedGoogle Scholar
  50. 50.
    Bartsch T, Goadsby PJ: Increased responses in trigeminocervical nociceptive neurons to cervical input after stimulation of the dura mater. Brain 2003, 126:1801–1813.PubMedCrossRefGoogle Scholar
  51. 51.
    Bovim G, Sand I: Cervicogenic headache, migraine without aura and tension-type headache: diagnostic blockade of the greater occipital and supraorbital nerves. Pain 1992, 51:43–48.PubMedCrossRefGoogle Scholar
  52. 52.
    Peres MF, Stiles MA, Siow HC, et al.: Greater occipital nerve blockade for cluster headache. Cephalalgia 2002, 22:520–522.PubMedCrossRefGoogle Scholar
  53. 53.
    Katsarava Z, Lehnerdt G, Duda B, et al.: Sensitization of trigeminal nociception specific for migraine but not pain of sinusitis. Neurology 2002, 59:1450–1453. A study showing facilitation of the blink reflex response in patients with migraine, but not in patients with sinusitis, implying a specific sensitization in migraine.PubMedGoogle Scholar
  54. 54.
    Kaube H, Katsarava Z, Przywara S, et al.: Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus? Neurology 2002, 58:1234–1238.PubMedGoogle Scholar
  55. 55.
    Burstein R, Yarnitsky D, Goor-Aryeh I, et al.: An association between migraine and cutaneous allodynia. Ann Neurol 2000, 47:614–624.PubMedCrossRefGoogle Scholar
  56. 56.
    Behbehani MM: Functional characteristics of the midbrain periaqueductal gray. Prog Neurobiol 1995, 46:575–605.PubMedCrossRefGoogle Scholar
  57. 57.
    Sandkuhler J, Fu QG, Zimmermann M: Spinal pathways mediating tonic or stimulation-produced descending inhibition from the periaqueductal gray or nucleus raphe magnus are separate in the cat. J Neurophysiol 1987, 58:327–341.PubMedGoogle Scholar
  58. 58.
    Fields HL, Heinricher MM: Anatomy and physiology of a nociceptive modulatory system. Philos Trans R Soc Lond B Biol Sci 1985, 308:361–374.PubMedGoogle Scholar
  59. 59.
    Fields HL, Heinricher MM, Mason P: Neurotransmitters in nociceptive modulatory circuits. Ann Rev Neurosci 1991, 14:219–245.PubMedCrossRefGoogle Scholar
  60. 60.
    Keay KA, Bandler R: Vascular head pain selectively activates ventrolateral periaqueductal gray in the cat. Neurosci Lett 1998, 245:58–60.PubMedCrossRefGoogle Scholar
  61. 61.
    Hoskin KL, Bulmer DC, Lasalandra M, et al.: Fos expression in the midbrain periaqueductal grey after trigeminovascular stimulation. J Anat 2001, 197:29–35.CrossRefGoogle Scholar
  62. 62.
    Knight YE, Bartsch T, Kaube H, Goadsby PJ: P/Q-type calcium channel blockade in the PAG facilitates trigeminal nociception: a functional genetic link for migraine? J Neurosci 2002, 22:1–6. Experimental study demonstrating (for the first time) blockade of P/Qtype voltage-gated calcium channels in the midbrain PAG facilitating trigeminal dural nociception. A particularly interesting study because missense mutations in these channels are pathogenic in familial hemiplegic migraine.Google Scholar
  63. 63.
    Knight YE, Goadsby PJ: The periaqueductal gray matter modulates trigeminovascular input: a role in migraine? Neuroscience 2001, 106:793–800.PubMedCrossRefGoogle Scholar
  64. 64.
    Urban MO, Gebhart GF: Supraspinal contributions to hyperalgesia. PNAS 1999, 96:7687–7692.PubMedCrossRefGoogle Scholar
  65. 65.
    Lin Q, Wu J, Peng YB, et al.: Nitric oxide-mediated spinal disinhibition contributes to the sensitization of primate spinothalamic tract neurons. J Neurophysiol 1999, 81:1086–1094.PubMedGoogle Scholar
  66. 66.
    Ren K, Dubner R: Descending modulation in persistent pain: an update. Pain 2002, 100:1–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Ophoff RA, Terwindt GM, Vergouwe MN, et al.: Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996, 87:543–552.PubMedCrossRefGoogle Scholar
  68. 68.
    Hans M, Luvisetto S, Williams ME, et al.: Functional consequences of mutations in the human alpha(1A) calcium channel subunit linked to familial hemiplegic migraine. J Neurosci 1999, 19:1610–1619.PubMedGoogle Scholar
  69. 69.
    May A, Ophoff RA, Terwindt GM, et al.: Familial hemiplegic migraine locus on chromosome 19p13 is involved in common forms of migraine with and without aura. Hum Genet 1995, 96:604–608.PubMedCrossRefGoogle Scholar
  70. 70.
    Terwindt GM, Ophoff RA, van Eijk R, et al.: Involvement of the CACNA1A gene containing region on 19p13 in migraine with and without aura. Neurology 2001, 56:1028–1032.PubMedGoogle Scholar
  71. 71.
    Weiller C, May A, Limmroth V, et al.: Brain stem activation in spontaneous human migraine attacks. Nat Med 1995, 1:658–660.PubMedCrossRefGoogle Scholar
  72. 72.
    Matharu MS, Bartsch T, Ward N, et al.: Central modulation in chronic migraine with implanted suboccipital stimulators. Neurology 2003, 60(suppl 1):A404-A405.Google Scholar
  73. 73.
    May A, Kaube H, Buechel C, et al.: Experimental cranial pain elicited by capsaicin: a PET-study. Pain 1998, 74:61–66.PubMedCrossRefGoogle Scholar
  74. 74.
    Knight YE, Bartsch T, Goadsby PJ: Trigeminal antinociception induced by bicuculline in the periaqueductal grey (PAG) is not affected by PAG P/Q-type calcium channel blockade in rat. Neurosci Lett 2003, 336:113–116.PubMedCrossRefGoogle Scholar
  75. 75.
    Richter F, Ebersberger A, Mikulik O, Schaible HG: P/Q-type channels in the brainstem regulate activity of neurons with input from the dura by controlling GABA release from inhibitory interneurons. Soc Neurosci [Abstract] 2002, 28:349:13.Google Scholar

Copyright information

© Current Science Inc 2003

Authors and Affiliations

  • T. Bartsch
  • Peter J. Goadsby
    • 1
  1. 1.Institute of NeurologyLondonUK

Personalised recommendations