Migraine and Autonomic Dysfunction: Which Is the Horse and Which Is the Jockey?


Purpose of Review

Symptoms of autonomic dysfunction are common in patients with migraine, both during and between migraine attacks. Studies evaluating objective autonomic testing in patients have found significant, though somewhat conflicting results. The purposes of this review are to summarize and interpret the key findings of these studies, including those evaluating heart rate variability, autonomic reflex testing, and functional imaging in patients with migraine. The neuroanatomy of the central autonomic network as it relates to migraine is also reviewed.

Recent Findings

Several studies have evaluated autonomic balance in migraineurs, with conflicting results on the magnitude of sympathetic versus parasympathetic dysfunction. Most studies demonstrate sympathetic impairment, with a lesser degree of parasympathetic impairment.


Three trends have emerged: (1) migraine with aura tends to produce more significant autonomic dysfunction than migraine without aura, (2) sympathetic impairment is more common than parasympathetic impairment, and (3) sympathetic impairment is common in the interictal period, with increased sympathetic responsiveness during the ictal period, suggesting adrenoreceptor hypersensitivity.

This is a preview of subscription content, log in to check access.

Fig. 1


Papers of particular interest, published recently, have been highlighted as: • Of importance.

  1. 1.

    Sacks O. Migraine; the evolution of a common disorder, [Internet]. University of California Press. 1973. [cited 2017 Nov 11]. 220 p. Available from: http://lmldb.stanford.edu/cgi-bin/Pwebrecon.cgi?BBRecID=42881&v2=1&SEQ=20171111223137&PID=xilessHzzeUvtJbHUN4TvFYbjbchR.

  2. 2.

    Cernuda-Morollón E, Martínez-Camblor P, Alvarez R, Larrosa D, Ramón C, Pascual J. Increased VIP levels in peripheral blood outside migraine attacks as a potential biomarker of cranial parasympathetic activation in chronic migraine. Cephalalgia [Internet]. 2015 [cited 2017 Nov 12];35(4):310–6. Available from: http://journals.sagepub.com/doi/10.1177/0333102414535111.

  3. 3.

    • Curfman D, Chilungu M, Daroff RB, Alshekhlee A, Chelimsky G, Chelimsky TC. Syncopal migraine. Clin Auton Res [Internet]. 2012 [cited 2017 Nov 15];22(1):17–23. Available from: http://link.springer.com/10.1007/s10286-011-0141-7. Interesting study that suggests that syncope may have a migrainous basis.

  4. 4.

    • Benarroch EE. The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clin Proc [Internet]. 1993 [cited 2017 Nov 11];68(10):988–1001. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8412366. Detailed review of the central autonomic network.

  5. 5.

    Benarroch EE. Pain-autonomic interactions. Neurol Sci [Internet]. 2006 [cited 2017 Nov 11];27 Suppl 2(S2):S130–3. Available from: http://link.springer.com/10.1007/s10072-006-0587-x

  6. 6.

    • Cutrer F. Pathophysiology of migraine. Semin Neurol [Internet]. 2010 [cited 2017 Nov 15];30(2):120–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20352582. Seminal review of migraine pathophysiology.

  7. 7.

    Evers S. Sleep and Headache: The Biological Basis. Headache J Head Face Pain [Internet]. 2010 [cited 2017 Nov 11];50(7):1246–51. Available from: http://doi.wiley.com/10.1111/j.1526-4610.2010.01730.x.

  8. 8.

    Goadsby PJ, Hoskin KL. The distribution of trigeminovascular afferents in the nonhuman primate brain Macaca nemestrina: a c-fos immunocytochemical study. J Anat [Internet]. 1997 [cited 2017 Nov 15];190 ( Pt 3):367–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9147223.

  9. 9.

    Zhu S, Marmura MJ. Non-invasive neuromodulation for headache disorders. Curr Neurol Neurosci Rep [Internet]. 2016 [cited 2017 Nov 12];16(2):11. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26750126.

  10. 10.

    Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia [Internet]. 1998 [cited 2017 Nov 12];39(7):677–86. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9670894.

  11. 11.

    • Koenig J, Williams DP, Kemp AH, Thayer JF. Vagally mediated heart rate variability in headache patients—a systematic review and meta-analysis. Cephalalgia [Internet]. 2016 [cited 2017 Nov 12];36(3):265–78. Available from: http://journals.sagepub.com/doi/10.1177/0333102415583989. Recent meta-analysis that reviews several HRV studies in migraine, demonstrating reduced parasympathetic tone.

  12. 12.

    Pogacnik T, Sega S, Pecnik B, Kiauta T. Autonomic function testing in patients with migraine. Headache [Internet]. [cited 2017 Nov 12];33(10):545–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8294192.

  13. 13.

    Mosek A, Novak V, Opfer-Gehrking TL, Swanson JW, Low PA. Autonomic dysfunction in migraineurs. Headache J Head Face Pain [Internet]. 1999 [cited 2017 Nov 8];39(2):108–17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15613203.

  14. 14.

    • Gotoh F, Komatsumoto S, Araki N, Gomi S. Noradrenergic nervous activity in migraine. Arch Neurol [Internet]. 1984 [cited 2017 Nov 11];41(9):951–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6477230. Detailed study that suggests that patients with migraine may have adrenoreceptor hypersensitivity due to noradrenergic deficiency.

  15. 15.

    Boccuni M, Alessandri M, Fusco BM, Cangi F. The pressor hyperresponsiveness to phenylephrine unmasks sympathetic hypofunction in migraine. [cited 2017 Nov 14]; Available from: http://journals.sagepub.com.laneproxy.stanford.edu/doi/pdf/10.1046/j.1468-2982.1989.0904239.x.

  16. 16.

    Matei D, Constantinescu V, Corciova C, Ignat B, Matei R, Popescu CD. Autonomic impairment in patients with migraine. Eur Rev Med Pharmacol Sci [Internet]. 2015 [cited 2017 Nov 5];19(20):3922–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26531280.

  17. 17.

    • Havanka-Kanniainen H. Cardiovascular reflex responses during migraine attack. Headache [Internet]. 1986 [cited 2017 Nov 12];26(9):442–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3781830. One of few studies that evaluated autonomic parameters in patients during the ictal period. The authors demonstrated that even while patients are demonstrating symptoms of autonomic impairment, their autonomic reflex testing was normal.

  18. 18.

    Koenig J, Williams DP, Kemp AH, Thayer JF. Vagally mediated heart rate variability in headache patients—a systematic review and meta-analysis. Cephalalgia [Internet]. 2016 [cited 2017 Nov 11];36(3):265–78. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25962595.

  19. 19.

    Thomsen LL, Iversen HK, Boesen F, Olesen J. Transcranial Doppler and cardiovascular responses during cardiovascular autonomic tests in migraineurs during and outside attacks. Brain [Internet]. 1995 [cited 2017 Nov 11];118 ( Pt 5):1319–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7496789.

  20. 20.

    Vollono C, Gnoni V, Testani E, Dittoni S, Losurdo A, Colicchio S, et al. Heart rate variability in sleep-related migraine without aura. J Clin Sleep Med [Internet]. 2013 [cited 2017 Nov 15];9(7):707–14. Available from: http://jcsm.aasm.org/ViewAbstract.aspx?pid=29036.

  21. 21.

    Boccuni M, Alessandri M, Fusco BM, Cangi F. The pressor hyperresponsiveness to phenylephrine unmasks sympathetic hypofunction in migraine. Cephalalgia [Internet]. 1989 [cited 2017 Nov 11];9(4):239–45. Available from: http://cep.sagepub.com/cgi/doi/10.1046/j.1468-2982.1989.0904239.x.

  22. 22.

    Mamontov O V, Babayan L, Amelin A V, Giniatullin R, Kamshilin AA. Autonomous control of cardiovascular reactivity in patients with episodic and chronic forms of migraine. J Headache Pain [Internet]. 2016 [cited 2017 Nov 5];17:52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27167136.

  23. 23.

    • Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G. Hypothalamic activation in spontaneous migraine attacks. Headache [Internet]. 2007 [cited 2017 Nov 14];47(10):1418–26. Available from: http://doi.wiley.com/10.1111/j.1526-4610.2007.00776. Functional imaging study that utilized PET to visualize metabolic activity during the ictal period, demonstrating increased activity in the hypothalamus.

  24. 24.

    Moulton EA, Becerra L, Johnson A, Burstein R, Borsook D. Altered hypothalamic functional connectivity with autonomic circuits and the locus coeruleus in migraine. Marinazzo D, editor. PLoS One [Internet]. 2014 [cited 2017 Nov 12];9(4):e95508. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24743801.

  25. 25.

    Thijs RD, Kruit MC, van Buchem MA, Ferrari MD, Launer LJ, van Dijk JG. Syncope in migraine: the population-based CAMERA study. Neurology [Internet]. 2006 [cited 2017 Nov 15];66(7):1034–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16606915.

  26. 26.

    Khurana RK, Eisenberg L. Orthostatic and non-orthostatic headache in postural tachycardia syndrome. Cephalalgia [Internet]. 2011 [cited 2017 Nov 10];31(4):409–15. Available from: http://journals.sagepub.com/doi/10.1177/0333102410382792.

  27. 27.

    Thieben MJ, Sandroni P, Sletten DM, Benrud-Larson LM, Fealey RD, Vernino S, et al. Postural orthostatic tachycardia syndrome: the Mayo clinic experience. Mayo Clin Proc [Internet]. 2007[cited 2017 Nov 10];82(3):308–13. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0025619611610276.

Download references

Author information



Corresponding author

Correspondence to Mitchell G. Miglis.

Ethics declarations

Conflict of Interest

Mitchell G. Miglis declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Migraine and Beyond

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Miglis, M.G. Migraine and Autonomic Dysfunction: Which Is the Horse and Which Is the Jockey?. Curr Pain Headache Rep 22, 19 (2018). https://doi.org/10.1007/s11916-018-0671-y

Download citation


  • Migraine
  • Autonomic
  • HRV
  • Tilt table
  • Valsalva
  • Syncope
  • POTS dysautonomia
  • Sympathetic
  • Parasympathetic