Current Pain and Headache Reports

, Volume 10, Issue 3, pp 231–238 | Cite as

Cutaneous allodynia and migraine: Another view

  • Carl Dahlöf


The paradigm of early treatment of the migraine attack at mild pain intensity has become one alternative to circumventing the problem of compromised oral absorption of symptomatic drugs due to migraine-induced gastrointestinal dysmotility. Early treatment also has been proposed to be advantageous because most migraineurs could be less responsive to delayed treatment, owing to the development of central sensitization of the trigeminal pain transmission. Ranking the underlying principles, it seems that the improved response to an oral triptan formulation at mild migraine symptom intensity has more to do with less impaired gastrointestinal absorption in the early stage of the attack than decreasing the time and preventing chances for central sensitization and development of cutaneous allodynia. Furthermore, parenteral administration of a triptan is always more likely to provide relief of symptoms than conventional tablets, even when it is used later in the course of the migraine attack. Individually tailored use of the available triptan formulations will increase, without any doubt, the within-migraineur consistency of response. It also will reduce the overall proportion of migraine attacks or migraineurs not responding to triptan treatment. Notwithstanding, the recommendation of early treatment during the migraine attack when the pain is mild remains valid.


Migraine Sumatriptan Migraine Attack Central Sensitization Zolmitriptan 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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References and Recommended Reading

  1. 1.
    Headache Classification Committee of The International Headache Society: The International Classification of Headache Disorders, edn 2. Cephalalgia 2004, 1:9–160.Google Scholar
  2. 2.
    Sanchez del Rio M, Reuter U: Pathophysiology of headache. Curr Neurol Neurosci Rep 2003, 3:109–114.PubMedGoogle Scholar
  3. 3.
    Bussone G: Pathophysiology of migraine. Neurol Sci 2004, 25(suppl 3):S239-S241.PubMedCrossRefGoogle Scholar
  4. 4.
    Silberstein SD: Migraine pathophysiology and its clinical implications. Cephalalgia 2004, 24(suppl 2):2–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Burstein R, Jakubowski M: Unitary hypothesis for multiple triggers of the pain and strain of migraine. J Comp Neurol 2005, 493:9–14. An interesting proposal of a neuroanatomical roadmap by which the trigeminovascular pathway by means of bidirectional trafficing can activate the same brain areas that have triggered its own activity.PubMedCrossRefGoogle Scholar
  6. 6.
    Buzzi MG, Moskowitz MA. The pathophysiology of migraine: year 2005. J Headache Pain 2005, 6:105–111.PubMedCrossRefGoogle Scholar
  7. 7.
    Goadsby PJ: Migraine pathophysiology. Headache 2005, 45(suppl 1):S14-S24.PubMedCrossRefGoogle Scholar
  8. 8.
    Waeber C, Moskowitz MA: Migraine as an infiammatory disorder. Neurology 2005, 64(suppl 2):S9-S15.PubMedGoogle Scholar
  9. 9.
    Olesen J, Jansen-Olesen I: Nitric oxide mechanisms in migraine. Pathol Biol 2000, 48:648–657.PubMedGoogle Scholar
  10. 10.
    Yetkin E, Ozisik H, Ozcan C, et al.: Decreased endotheliumdependent vasodilatation in patients with migraine: a new aspect to vascular pathophysiology of migraine. Coron Artery Dis 2006, 17:29–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Welch KM: Concepts of migraine headache pathogenesis: insights into mechanisms of chronicity and new drug targets. Neurol Sci 2003, 24:S149-S153.PubMedCrossRefGoogle Scholar
  12. 12.
    Welch KM: Contemporary concepts of migraine pathogenesis. Neurology 2003, 61(suppl 4):S2-S8.PubMedGoogle Scholar
  13. 13.
    Nedeltchev K, Arnold M, Schwerzmann M, et al.: Cerebrovascular response to repetitive visual stimulation in interictal migraine with aura. Cephalalgia 2004, 24:700–706.PubMedCrossRefGoogle Scholar
  14. 14.
    Welch KM: Brain hyperexcitability: the basis for antiepileptic drugs in migraine prevention. Headache 2005, 45(suppl 1):S25-S32.PubMedCrossRefGoogle Scholar
  15. 15.
    Valeriani M, Rinalduzzi S, Vigevano F: Multilevel somatosensory system disinhibition in children with migraine. Pain 2005, 118:137–144.PubMedCrossRefGoogle Scholar
  16. 16.
    Gupta VK: Migraine, cortical excitability, and evoked potentials: a clinico-pharmacological perspective. Brain 2005, 128:E36; author reply E37.PubMedCrossRefGoogle Scholar
  17. 17.
    Drummond PD: Triggers of motion sickness in migraine sufferers. Headache 2005, 45:653–656.PubMedCrossRefGoogle Scholar
  18. 18.
    de Tommaso M, Lo Sito L, Di Fruscolo O, et al.: Lack of habituation of nociceptive evoked responses and pain sensitivity during migraine attack. Clin Neurophysiol 2005, 116:1254–1264.PubMedCrossRefGoogle Scholar
  19. 19.
    de Tommaso M: Central nervous system excitability in migraine: Who is right? Pain 2005, 118:1–2.PubMedCrossRefGoogle Scholar
  20. 20.
    Kroner-Herwig B, Ruhmland M, Zintel W, Siniatchkin M: Are migraineurs hypersensitive? A test of the stimulus processing disorder hypothesis. Eur J Pain 2005, 9:661–671.PubMedCrossRefGoogle Scholar
  21. 21.
    Custers A, Mulleners WM, Chronicle EP: Assessing cortical excitability in migraine: reliability of magnetic suppression of perceptual accuracy technique over time. Headache 2005, 45:1202–1207.PubMedCrossRefGoogle Scholar
  22. 22.
    Coppola G, Vandenheede M, Di Clemente L, et al.: Somatosensory evoked high-frequency oscillations refiecting thalamo-cortical activity are decreased in migraine patients between attacks. Brain 2005, 128:98–103.PubMedCrossRefGoogle Scholar
  23. 23.
    Bowyer SM, Mason KM, Moran JE, et al.: Cortical hyperexcitability in migraine patients before and after sodium valproate treatment. J Clin Neurophysiol 2005, 22:65–67.PubMedCrossRefGoogle Scholar
  24. 24.
    Ambrosini A, Schoenen J: The electrophysiology of migraine. Curr Opin Neurol 2003, 16:327–331.PubMedCrossRefGoogle Scholar
  25. 25.
    Mayberg M, Langer RS, Zervas NT, Moskowitz MA: Perivascular meningeal projections from cat trigeminal ganglia: possible pathway for vascular headaches in man. Science 1981, 213:228–230.PubMedCrossRefGoogle Scholar
  26. 26.
    Keller JT, Van Loveren H: Pathophysiology of the pain of trigeminal neuralgia and atypical facial pain: a neuroanatomical perspective. Clin Neurosurg 1985, 32:275–293.PubMedGoogle Scholar
  27. 27.
    Bartsch T, Goadsby PJ: Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input. Brain 2002, 125:1496–1509.PubMedCrossRefGoogle Scholar
  28. 28.
    Bartsch T: Migraine and the neck: new insights from basic data. Curr Pain Headache Rep 2005, 9:191–196.PubMedGoogle Scholar
  29. 29.
    Zagami AS, Lambert GA: Craniovascular application of capsaicin activates nociceptive thalamic neurones in the cat. Neurosci Lett 1991, 121:187–190.PubMedCrossRefGoogle Scholar
  30. 30.
    Zagami AS, Goadsby PJ, Edvinsson L: Stimulation of the superior sagittal sinus in the cat causes release of vasoactive peptides. Neuropeptides 1990, 16:69–75.PubMedCrossRefGoogle Scholar
  31. 31.
    Busch V, Jakob W, Juergens T, et al.: Functional connectivity between trigeminal and occipital nerves revealed by occipital nerve blockade and nociceptive blink refiexes. Cephalalgia 2006, 26:50–55. A neurophysiologic study providing evidence for a functional connectivity between the sensory occipital (C2-) segments and the ophthalmaic branch of the trigeminal nociceptive system in humans.PubMedCrossRefGoogle Scholar
  32. 32.
    Kerr FW, Olafson RA: Trigeminal and cervical volleys: convergence on single units in the spinal gray at C-1 and C-2. Arch Neurol 1961, 5:171–178.PubMedGoogle Scholar
  33. 33.
    Liveing E: On Megrim, Sick Headache, and Some Allied Disorders: A contribution to the Pathology of Nerve Storms. Nijmegen: Arts & Boeve Publishers (Facsimlie reprint 1997); 1873.Google Scholar
  34. 34.
    Selby G, Lance JW: Observations on 500 cases of migraine and allied vascular headache. J Neurol Neurosurg Psychiatry 1960, 23:23–32.PubMedCrossRefGoogle Scholar
  35. 35.
    Drummond PD: Scalp tenderness and sensitivity to pain in migraine and tension headache. Headache 1987, 27:45–50.PubMedCrossRefGoogle Scholar
  36. 36.
    Burstein R: Deconstructing migraine headache into peripheral and central sensitization. Pain 2001, 89:107–110.PubMedCrossRefGoogle Scholar
  37. 37.
    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, 123:1703–1709.PubMedCrossRefGoogle Scholar
  38. 38.
    Burstein R, Yarnitsky D, Goor-Aryeh I, et al.: An association between migraine and cutaneous allodynia. Ann Neurol 2000, 47:614–624.PubMedCrossRefGoogle Scholar
  39. 39.
    Burstein R, Jakubowski M: Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization. Ann Neurol 2004, 55:27–36.PubMedCrossRefGoogle Scholar
  40. 40.
    Blau JN, Solomon F: Smell and other sensory disturbances in migraine. J Neurol 1985, 232:275–276.PubMedCrossRefGoogle Scholar
  41. 41.
    Waelkens J: Warning symptoms in migraine: characteristics and therapeutic implications. Cephalalgia 1985, 5:223–228.PubMedCrossRefGoogle Scholar
  42. 42.
    Linde M, Elam M, Lundblad L, et al.: Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia. Cephalalgia 2004, 24:1057–1066.PubMedCrossRefGoogle Scholar
  43. 43.
    Burstein R, Collins B, Jakubowski M: Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol 2004, 55:19–26.PubMedCrossRefGoogle Scholar
  44. 44.
    Ashkenazi A, Young WB: Dynamic mechanical (brush) allodynia in cluster headache. Headache 2004, 44:1010–1012.PubMedCrossRefGoogle Scholar
  45. 45.
    Jakubowski M, Silberstein S, Ashkenazi A, Burstein R: Can allodynic migraine patients be identified interictally using a questionnaire? Neurology 2005, 65:1419–1422.PubMedCrossRefGoogle Scholar
  46. 46.
    Levy D, Jakubowski M, Burstein R: Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists. Proc Natl Acad Sci U S A 2004, 101:4274–4279.PubMedCrossRefGoogle Scholar
  47. 47.
    Jakubowski M, Levy D, Goor-Aryeh I, et al.: Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors. Headache 2005, 45:850–861.PubMedCrossRefGoogle Scholar
  48. 48.
    Ferrari M, Goadsby P, Roon K, Lipton R: Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia 2002, 22:633–658.PubMedCrossRefGoogle Scholar
  49. 49.
    Dahlöf C: Integrating the triptans into clinical practice. Curr Opin Neurol 2002, 15:317–322.PubMedCrossRefGoogle Scholar
  50. 50.
    Silberstein SD: Migraine. Lancet 2004, 363:381–391.PubMedCrossRefGoogle Scholar
  51. 51.
    Barger G: Ergot and Ergotism: A Monograph. London: Gurney and Jackson; 1931.Google Scholar
  52. 52.
    Dahlöf C, Ekbom K, Persson L: Clinical experiences from Sweden on the use of subcutaneously administered sumatriptan in migraine and cluster headache. Arch Neurol 1994, 51:1256–1261.PubMedGoogle Scholar
  53. 53.
    Black P, Caldwell J: Skin sensitivity to sumatriptan. N Z Med J 1994, 107:20–21.PubMedGoogle Scholar
  54. 54.
    Dahlöf CG: How does sumatriptan perform in clinical practice? Cephalalgia 1995, 15(suppl 15):21–28.PubMedGoogle Scholar
  55. 55.
    Visser WH, de Vriend RH, Jaspers NH, Ferrari MD: Sumatriptannonresponders: a survey in 366 migraine patients. Headache 1996, 36:471–475.PubMedCrossRefGoogle Scholar
  56. 56.
    Dahlöf CG, Mathew N: Cardiovascular safety of 5HT1B/1D agonists: Is there a cause for concern? Cephalalgia 1998, 18:539–545.PubMedCrossRefGoogle Scholar
  57. 57.
    Dahlöf CG, Saiers J: Sumatriptan injection and tablets in clinical practice: results of a survey of 707 migraineurs. Headache 1998, 38:756–763.PubMedCrossRefGoogle Scholar
  58. 58.
    Burstein R, Jakubowski M, Levy D: Anti-migraine action of triptans is preceded by transient aggravation of headache caused by activation of meningeal nociceptors. Pain 2005, 115:21–28.PubMedCrossRefGoogle Scholar
  59. 59.
    Visser WH, de Vriend RH, Jaspers MW, Ferrari MD: Sumatriptan in clinical practice: a 2-year review of 453 migraine patients. Neurology 1996, 47:46–51.PubMedGoogle Scholar
  60. 60.
    Visser WH, Jaspers NM, de Vriend RH, Ferrari MD: Chest symptoms after sumatriptan: a two-year clinical practice review in 735 consecutive migraine patients. Cephalalgia 1996, 16:554–559.PubMedCrossRefGoogle Scholar
  61. 61.
    Dahlöf CG: Non-oral formulations of triptans and their use in acute migraine. Curr Pain Headache Rep 2005, 9:206–212.PubMedGoogle Scholar
  62. 62.
    Dahlöf CG: Sumatriptan: pharmacological basis and clinical results. Curr Med Res Opin 2001, 17:s35-s45.PubMedCrossRefGoogle Scholar
  63. 63.
    Dahlöf CG, Lipton RB, Lines CR, et al.: Consistency of pain relief over multiple migraine attacks following treatment with rizatriptan. In Frontiers in Headache Research—The Triptans: Novel Drugs for Migraine: Edited by Olesen J, Ferrari M, Humphrey PP. Oxford: Oxford University Press; 2001:222–227.Google Scholar
  64. 64.
    Ifergane G, Wirgguin I, Shvartzman P: Triptans: Why once? Headache 2006, in pressGoogle Scholar
  65. 65.
    Dahlöf C, Jones M, Davis K, et al.: A comparison of preference for and efficacy of tablet formulations of sumatriptan (50 mg and 100 mg), naratriptan (2.5 mg), rizatriptan (10 mg) and zolmitriptan 2.5 mg) in the acute treatment of migraine. J Headache Pain 2004, 5:115–122.Google Scholar
  66. 66.
    Lipton RB, Stewart WF: Acute migraine therapy: Do doctors understand what patients with migraine want from therapy? Headache 1999, 39(suppl 2):S20-S26.CrossRefGoogle Scholar
  67. 67.
    Dahlöf CG: Characteristics of different routes of administration. In Frontiers in Headache Research—The Triptans: Novel Drugs for Migraine. Edited by Olesen J, Ferrari M, Humphrey PP. Oxford: Oxford University Press; 2001:80–90.Google Scholar
  68. 68.
    MacGregor EA, Brandes J, Eikermann A: Migraine prevalence and treatment patterns: the global Migraine and Zolmitriptan Evaluation survey. Headache 2003, 43:19–26.PubMedCrossRefGoogle Scholar
  69. 69.
    Dahlöf CG, Hargreaves RJ: Pathophysiology and pharmacology of migraine: Is there a place for antiemetics in future treatment strategies? Cephalalgia 1998, 18:593–604.PubMedCrossRefGoogle Scholar
  70. 70.
    Kaufman JS, Levine I: Acute gastric dilatation of stomach during attack of migraine. Radiology 1936, 27:301–302.Google Scholar
  71. 71.
    Volans GN: Migraine and drug absorption. Clin Pharmacokinet 1978, 3:313–318.PubMedGoogle Scholar
  72. 72.
    Tokola RA, Kangasniemi P, Neuvonen PJ, Tokola O: Tolfenamic acid, metoclopramide, caffeine, and their combinations in the treatment of migraine attacks. Cephalalgia 1984, 4:253–263.PubMedCrossRefGoogle Scholar
  73. 73.
    Tokola RA, Neuvonen PJ: Effects of migraine attack and metoclopramide on the absorption of tolfenamic acid. Br J Clin Pharmacol 1984, 17:67–75.PubMedGoogle Scholar
  74. 74.
    Houghton LA, Fowler P, Keene ON, Read NW: Effect of sumatriptan, a new selective 5HT1-like agonist, on liquid gastric emptying in man. Aliment Pharmacol Ther 1992, 6:685–691.PubMedCrossRefGoogle Scholar
  75. 75.
    Tack J: The physiology and the pathophysiology of the gastric accommodation refiex in man. Verh K Acad Geneeskd Belg 2000, 62:183–207.PubMedGoogle Scholar
  76. 76.
    Cipolla G, Sacco S, Crema F, et al.: Gastric motor effects of triptans: open questions and future perspectives. Pharmacol Res 2001, 43:205–210.PubMedCrossRefGoogle Scholar
  77. 77.
    Sheftell FD, Dahlöf CG, Brandes JL, et al.: Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets. Clin Ther 2005, 27:407–417.PubMedCrossRefGoogle Scholar
  78. 78.
    Schoenen J: When should triptans be taken during a migraine attack? CNS Drugs 2001, 15:583–587.PubMedCrossRefGoogle Scholar
  79. 79.
    Cady RK, Lipton RB, Hall C, et al.: Treatment of mild headache in disabled migraine sufferers: results of the Spectrum Study. Headache 2000, 40:792–797.PubMedCrossRefGoogle Scholar
  80. 80.
    Hu XH, Raskin NH, Cowan R, et al.: Treatment of migraine with rizatriptan: when to take the medication. Headache 2002, 42:16–20.PubMedCrossRefGoogle Scholar
  81. 81.
    Pascual J: Clinical benefists of early triptan therapy for migraine. Headache 2002, 1:10–17.CrossRefGoogle Scholar
  82. 82.
    Mathew NT, Kailasam J, Meadors L: Early treatment of migraine with rizatriptan: a placebo-controlled study. Headache 2004, 44:669–673.PubMedCrossRefGoogle Scholar
  83. 83.
    Klapper J, Lucas C, Rosjo O, Charlesworth B: Benefits of treating highly disabled migraine patients with zolmitriptan while pain is mild. Cephalalgia 2004, 24:918–924.PubMedCrossRefGoogle Scholar
  84. 84.
    Diener HC: Eletriptan in migraine. Expert Rev Neurother 2005, 5:43–53.PubMedCrossRefGoogle Scholar
  85. 85.
    Winner P, Landy S, Richardson M, Ames M: Early inter vention in migraine with sumatriptan tablets 50 mg versus 100 mg: a pooled analysis of data from six clinical trials. Clin Ther 2005, 27:1785–1794.PubMedCrossRefGoogle Scholar
  86. 86.
    Linde M, Mellberg A, Dahlöf C: Subcutaneous sumatriptan provides symptomatic relief at any pain intensity or time during the migraine attack. Cephalalgia 2006, 26:113–121. Delayed administration of subcutaneous sumatriptan by almost 6 hours does not impair efficacy.PubMedCrossRefGoogle Scholar
  87. 87.
    Diamond S, Freitag FG: Sumatriptan 6 mg subcutaneous as a successful treatment for migraine associated with allodynia. Neurology 2004, 62(suppl 5):A149.Google Scholar
  88. 88.
    Freitag FG, Diamond S: Sumatriptan 6 mg subcutaneous as an effective migraine treatment in patients who historically fail to respond to oral triptans. Neurology 2004, 62 (suppl 5):A150.Google Scholar

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© Current Science Inc 2006

Authors and Affiliations

  1. 1.Gothenburg Migraine ClinicGothenburgSweden

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