The Role of Adenosine Signaling in Headache: A Review
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Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA
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Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA 19107, USA
4
National Institutes of Health, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Stephanie Nahas
Brain Sci. 2017, 7(3), 30; https://doi.org/10.3390/brainsci7030030
Received: 28 December 2016
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Revised: 5 March 2017
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Accepted: 7 March 2017
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Published: 13 March 2017
(This article belongs to the Special Issue The Pathogenesis and Treatment of Headache Disorders)
Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments. In this review, we highlight evidence that supports the involvement of adenosine signaling in different forms of headache, headache triggers, and basic headache physiology. This evidence supports adenosine A2A receptors as a critical adenosine receptor subtype involved in headache pain. Adenosine A2A receptor signaling may contribute to headache via the modulation of intracellular Cyclic adenosine monophosphate (cAMP) production or 5' AMP-activated protein kinase (AMPK) activity in neurons and glia to affect glutamatergic synaptic transmission within the brainstem. This evidence supports the further study of adenosine signaling in headache and potentially illuminates it as a novel therapeutic target for migraine.
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Keywords:
migraine; headache; adenosine; adenosine receptors; mitochondria; astrocytes; trigeminal
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
MDPI and ACS Style
Fried, N.T.; Elliott, M.B.; Oshinsky, M.L. The Role of Adenosine Signaling in Headache: A Review. Brain Sci. 2017, 7, 30. https://doi.org/10.3390/brainsci7030030
AMA Style
Fried NT, Elliott MB, Oshinsky ML. The Role of Adenosine Signaling in Headache: A Review. Brain Sciences. 2017; 7(3):30. https://doi.org/10.3390/brainsci7030030
Chicago/Turabian StyleFried, Nathan T., Melanie B. Elliott, and Michael L. Oshinsky. 2017. "The Role of Adenosine Signaling in Headache: A Review" Brain Sciences 7, no. 3: 30. https://doi.org/10.3390/brainsci7030030
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