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  • Review Article
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Post-traumatic headache: epidemiology and pathophysiological insights

Nature Reviews Neurology volume 15, pages 607–617 (2019)Cite this article

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Abstract

Post-traumatic headache (PTH) is a highly disabling secondary headache disorder and one of the most common sequelae of mild traumatic brain injury, also known as concussion. Considerable overlap exists between PTH and common primary headache disorders. The most common PTH phenotypes are migraine-like headache and tension-type-like headache. A better understanding of the pathophysiological similarities and differences between primary headache disorders and PTH could uncover unique treatment targets for PTH. Although possible underlying mechanisms of PTH have been elucidated, a substantial void remains in our understanding, and further research is needed. In this Review, we describe the evidence from animal and human studies that indicates involvement of several potential mechanisms in the development and persistence of PTH. These mechanisms include impaired descending modulation, neurometabolic changes, neuroinflammation and activation of the trigeminal sensory system. Furthermore, we outline future research directions to establish biomarkers involved in progression from acute to persistent PTH, and we identify potential drug targets to prevent and treat persistent PTH.

Key points

  • Post-traumatic headache (PTH) is one of the most common sequelae of traumatic brain injury; the most common headache phenotypes in PTH are migraine-like headache and tension-type-like headache.

  • PTH is associated with somatic symptoms, including nausea, vomiting, photophobia and phonophobia, and cognitive and psychological symptoms.

  • Possible disease mechanisms of PTH include impaired descending modulation, neurometabolic changes and activation of the trigeminal sensory system.

  • The emphasis of future studies of PTH should be on establishing biomarkers of progression from acute PTH to persistent PTH.

  • Identification of potential treatment targets, such as calcitonin gene-related peptide, should enable randomized controlled trials to be conducted in patients with PTH.

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Fig. 1: Classification of headache attributed to trauma or injury to the head.
Fig. 2: Possible mechanisms underlying the pathophysiology of PTH.

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Acknowledgements

The authors thank PhD student T. P. Do, University of Copenhagen, for drawing a preliminary sketch of figure 2. No compensation was received for this contribution.

Authors contributions

All authors researched data for the article, discussed the content, wrote the text, and reviewed and edited the manuscript before submission.

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  1. These authors contributed equally: Henrik Winther Schytz, David W. Dodick

Authors and Affiliations

  1. Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Håkan Ashina, Faisal Mohammad Amin, Messoud Ashina & Henrik Winther Schytz

  2. Department of Pharmacology, University of Arizona, Tucson, Phoenix, AZ, USA

    Frank Porreca

  3. Department of Neurology, Mayo Clinic, Phoenix, AZ, USA

    Frank Porreca & David W. Dodick

  4. Department of Basic Medical Sciences, University of Arizona, Phoenix, AZ, USA

    Trent Anderson

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Competing interests

F.M.A. is a lecturer or scientific adviser for Novartis and Teva. M.A. is a consultant, speaker or scientific adviser for Alder, Allergan, Amgen, Eli Lilly, Novartis and Teva. H.W.S. is a lecturer for Novartis. D.W.D. reports the following competing interests: personal fees from Alder, Allergan, Amgen, Association of Translational Medicine, Autonomic Technologies, Aural Analytics, Biohaven, Charleston Laboratories, Daniel Edelman, Axsome, Dr Reddy’s Laboratories/Promius, Electrocore, Eli Lilly, eNeura, Foresite Capital, Impel, Ipsen, Neurolief, Nocira, Novartis, Oppenheimer, PSL Group Services, Satsuma, Sun Pharma (India), Supernus, Teva, Theranica, University of British Columbia, University Health Network, Vedanta, WL Gore, XoC, Zosano and ZP Opco; CME fees or royalty payments from Academy for Continued Healthcare Learning, Cambridge University Press, Chameleon, Global Access Meetings, Global Life Sciences, Global Scientific Communications, Haymarket, Healthlogix, Medicom Worldwide, Medlogix Communications, Mednet, Miller Medical, Oxford University Press, PeerView, Universal Meeting Management, UpToDate (Elsevier), WebMD Health/Medscape and Wolters Kluwer Health; stock options with Aural Analytics, Epien, GBS/Nocira, Healint, King-Devick Technologies, Matterhorn/Ontologics, Second Opinon/Mobile Health and Theranica; consulting without fee for Aural Analytics, Epien, Healint and Second Opinion/Mobile Health; position on the board of directors for Epien, King-Devick Technologies and Matterhorn/Ontologics; patent 17189376.1-1466: vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis without fee; research funding from American Migraine Foundation, Henry Jackson Foundation, Patient-Centered Outcomes Research Institute and US Department of Defence; professional society fees or reimbursement for travel from American Academy of Neurology, American Brain Foundation, American Headache Society, American Migraine Foundation, Canadian Headache Society and International Headache Society; and use agreement through employer for Myndshft. The other authors declare no competing interests.

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Review criteria

Articles discussed in this Review were identified by PubMed searches performed between 1 May 2018 and 1 September 2018 with no restrictions on the date of publication. The search terms used were ‘post-traumatic headache’, ‘PTH’, ‘concussion’, ‘traumatic brain injury’, ‘pathophysiology’ and ‘imaging’. The reference lists of identified papers were searched for further relevant articles, and related citations for identified papers as listed on the PubMed site were evaluated. The final references included were chosen based on the relevance to the scope of this Review.

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Ashina, H., Porreca, F., Anderson, T. et al. Post-traumatic headache: epidemiology and pathophysiological insights. Nat Rev Neurol 15, 607–617 (2019). https://doi.org/10.1038/s41582-019-0243-8

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