Migraine is a disabling neurological disorder most often characterized by the accompanying headache, but it is much more than just an episodic headache as it includes many other symptoms such as phonophobia, photophobia, nausea, and visual auras during the prodromal phase in a subset of patients. Headache is described as pain located above the orbitomeatal line that transects the head, approximately from the top of the eyes to the back of the skull. In this review, we present mounting evidence that demonstrates adenosine’s role in migraine and headache, revealing it as a potential therapeutic target for migraine and headache treatment. Now that migraine is thought to be a neurological and not a vascular disorder, caffeine’s common inclusion in migraine treatments suggests an alternative, non-vascular mechanism of action behind its efficacy in migraine patients. Caffeine was originally included in many migraine treatments due to the previous assumption that migraine was a vascular disorder. Combining caffeine with other treatments can improve pain relief by as much as 40% in patients. A component of some of these treatment options is caffeine, a non-specific adenosine receptor antagonist. Some patients who are non-responders to these treatments choose to undergo surgical implantation of invasive nerve stimulators to relieve pain. Ĭurrent treatment options for headache and migraine include analgesics, triptans, ergots, behavioral intervention, and nerve stimulation, while new treatments, such as monoclonal antibodies against Calcitonin gene-related peptide (CGRP) or the CGRP receptor and CGRP inhibitors, are under development. ![]() Although progress has been made in understanding adenosine’s role in certain pain states, less is known about how it is involved in migraine. Not surprisingly, adenosine is appreciated for its complex role in many nervous system disorders such as alcoholism, epilepsy, traumatic brain injury, ischemia, anxiety, Alzheimer’s disease, Parkinson’s, and brain cancer. This evidence supports the further study of adenosine signaling in headache and potentially illuminates it as a novel therapeutic target for migraine.Īdenosine is a purine nucleoside that plays a critical role in numerous cellular and molecular functions throughout the brain such as metabolism, cell signaling, purinergic neuronal signaling, and inflammation. Adenosine A 2A 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 adenosine A 2A receptors as a critical adenosine receptor subtype involved in headache pain. 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 is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. 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. ![]() ![]() ![]() Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete.
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