Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


Getting closer to a cure for migraine

In the past few years the scientific community has witnessed a prodigious surge in research activity, publication of data and progress in understanding the mechanistic components of migraine. This renaissance is the result of efforts initiated decades ago that are finally being translated into benefits for individuals affected by this disease.

Key advances

  • Trials have demonstrated that monoclonal antibodies that target calcitonin gene-related peptide 1 induce marked improvements (>75%) among a small but meaningful proportion of patients with chronic migraine1 or episodic migraine2.

  • Noninvasive vagal nerve stimulation delivered with two short-duration stimulations at the neck level has proved effective in the treatment of migraine attacks: one-third of patients achieved pain-free status at 2 h (ref.4).

  • Preclinical data support the idea that pituitary adenylate cyclase-activating polypeptide and its G-protein-coupled receptors are viable targets for new migraine treatments8.

  • Intriguing findings obtained in a migraine-specific animal model point to another potential pathway implicated in migraine pain: inhibition of acid-sensing ion channels prevents cephalic allodynia10.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Mechanism of action of monoclonal antibodies that target calcitonin gene-related peptide 1.


  1. 1.

    Ashina, M. et al. Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: a subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia 38, 1611–1621 (2018).

    Article  Google Scholar 

  2. 2.

    Stauffer, V. L. et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 75, 1080–1088 (2018).

    Article  Google Scholar 

  3. 3.

    Halker Singh, R. B. et al. Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab: post-hoc analyses from phase 2 trials. Cephalalgia (2018).

    Article  PubMed  Google Scholar 

  4. 4.

    Tassorelli, C. et al. Noninvasive vagus nerve stimulation as acute therapy for migraine: the randomized PRESTO study. Neurology 91, e364–e373 (2018).

    Article  Google Scholar 

  5. 5.

    Moeller, M., Schroeder, C. F. & May, A. Vagus nerve stimulation modulates the cranial trigeminal autonomic reflex. Ann. Neurol. 84, 886–892 (2018).

    Article  Google Scholar 

  6. 6.

    De Icco, R. et al. Peripheral vagal nerve stimulation modulates the nociceptive withdrawal reflex in healthy subjects: a randomized, cross-over, sham-controlled study. Cephalalgia 38, 1658–1664 (2018).

    Article  Google Scholar 

  7. 7.

    Vollesen, A. L., Guo, S. & Ashina, M. PACAP38 dose–response pilot study in migraine patients. Cephalalgia 37, 391–395 (2017).

    Article  Google Scholar 

  8. 8.

    Frederiksen, S. D., Warfvinge, K., Ohlsson, L. & Edvinsson, L. Expression of pituitary adenylate cyclase-activating peptide, calcitonin gene-related peptide and headache targets in the trigeminal ganglia of rats and humans. Neuroscience 393, 319–332 (2018).

    CAS  Article  Google Scholar 

  9. 9.

    Waschek, J. A., Baca, S. M. & Akerman, S. PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma. J. Headache Pain 19, 23 (2018).

    Article  Google Scholar 

  10. 10.

    Verkest, C. et al. Effects of systemic inhibitors of acid-sensing ion channels 1 (ASIC1) against acute and chronic mechanical allodynia in a rodent model of migraine. Br. J. Pharmacol. 175, 4154–4166 (2018).

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Cristina Tassorelli.

Ethics declarations

Competing interests

C.T. declares that she has received fees for serving on scientific advisory boards for Allergan, ElectroCore, Eli Lilly, Novartis and Teva. R.D.I. declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tassorelli, C., De Icco, R. Getting closer to a cure for migraine. Nat Rev Neurol 15, 64–65 (2019).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing