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How Excedrin Migraine Works

Migraines are more than just a bad headache. Here’s how this over-the-counter pain reliever can soothe your symptoms—fast.

Migraines are a complex neurovascular disorder. What does this mean? It means that the nerves and blood vessels are involved in the pathophysiology of a migraine. A migraine headache arises from activation of certain nerve cells which results in the release of inflammatory chemicals. This causes inflammation and swelling of the blood vessels in the head—activating the pain receptors that transmit pain signals to the brain and create the sensation of pain.1

When the telltale signs of a migraine strike—the pulsing or throbbing pain on one or both sides of your head, sensitivity to light or sound, nausea, and even a loss of vision—it can be downright scary.1 After all, this type of head pain is often debilitating, and symptoms can last anywhere from four to 72 hours.

Excedrin® Migraine contains three components: acetaminophen, aspirin, and caffeine, which help target pain in different ways. Research has demonstrated that not only is this combination of ingredients effective in treating migraines, but it is also significantly more effective than the individual components alone.2, 3 For exactly how it works, read on.

Aspirin Tames Pain-Causing Inflammation

A well-known non-steroidal anti-inflammatory that has been used for more than a century, aspirin works is by blocking the body’s production of prostaglandins in the peripheral nervous system. Prostaglandins are one of the inflammatory chemicals that cause the blood vessels to become inflamed and swell during a migraine attack.4 In general, aspirin helps to prevent the transmission of pain signals to the brain by stopping the production of prostaglandins.

Acetaminophen: The Tried-and-True Pain Reliever

Acetaminophen, like aspirin, also appears to inhibits enzymes in the body that produce pain-causing prostaglandins.4, 5 However, while aspirin inhibits prostaglandins in the peripheral nervous system, acetaminophen appears to focus its pain-fighting power in the central nervous system.5 While the way acetaminophen works is not fully understood, it is believed to elevate the pain threshold. This allows you to tolerate more pain, therefore providing pain relief.

Caffeine: The Amplifier

Caffeine has been shown to increase the potency of aspirin and acetaminophen—the two pain relievers in Excedrin® Migraine —by up to 40 percent.6 This means less acetaminophen and aspirin is needed to relieve your migraine pain when combined with caffeine.

Ease Your Migraine Pain With Excedrin® Migraine

Even though the cause of migraines is still largely unknown, and triggers vary from person to person, you should treat your migraines right away. One study found that a whopping 49 percent of migraine sufferers avoid or delay taking medications when they feel an attack coming on.7 Treating a migraine as soon as you feel pain leads to a better outcome.8 Be sure to talk to your doctor about your migraines and the best treatment plan for you.


  1. Silberstein, Stephen D. “Migraine - Neurologic Disorders.” Merck Manuals Professional Edition,
  2. Diener, H C, et al. “The Fixed Combination of Acetylsalicylic Acid, Paracetamol and Caffeine Is More Effective than Single Substances and Dual Combination for the Treatment of Headache: a Multicentre, Randomized, Double-Blind, Single-Dose, Placebo-Controlled Parallel Group Study.” Cephalalgia : an International Journal of Headache., U.S. National Library of Medicine, Oct. 2005,
  3. Lipton, Richard B. “Efficacy and Safety of Acetaminophen, Aspirin, and Caffeine in Alleviating Migraine Headache Pain.” Archives of Neurology, American Medical Association, 1 Feb. 1998,
  4. DeMaagd, George. “The Pharmacological Management Of Migraine, Part 1: Overview and Abortive Therapy.” Pharmacy and Therapeutics, MediMedia USA, Inc., July 2008,
  5. Sharma, Chhaya V, and Vivek Mehta. “Paracetamol: Mechanisms and Updates.” OUP Academic, Oxford University Press, 10 Oct. 2013,
  6. Laska, E M, et al. “Caffeine as an Analgesic Adjuvant.” JAMA., U.S. National Library of Medicine, 6 Apr. 1984,
  7. Foley, K A, et al. “Treating Early versus Treating Mild: Timing of Migraine Prescription Medications among Patients with Diagnosed Migraine.” Headache., U.S. National Library of Medicine, May 2005,
  8. “Migraine.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 26 Apr. 2017,


References: migraine treatmentscaffeine



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