Inflammation in Migraine…or Not…: A Critical Evaluation of the Evidence

Andrew Charles MD; Sinifunanya E. Nwaobi MD, PhD; Peter Goadsby MD, PhD

Disclosures

Headache. 2021;61(10):1575-1578. 

In This Article

Inflammation and Therapeutics

There is high-quality evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) as acute migraine therapies. The term "NSAIDs" does not adequately capture the remarkable range of effects these compounds have in addition to their anti-inflammatory mechanisms. Among these are inhibition of central trigeminal neurons,[35] generalized analgesia, modulation of vascular caliber, and inhibition of platelet aggregation.[36] Their therapeutic effect in migraine could, therefore, involve mechanisms distinct from inflammation. Corticosteroids, also well known for their anti-inflammatory action, are commonly used as a short-term migraine treatment, although with less evidence supporting their use.[37] As with NSAIDs, this potential efficacy as a migraine therapy is cited as evidence for a role for inflammation in migraine. Similar to NSAIDs, however, corticosteroids have a broad range of effects,[38] and there is no definitive evidence that any therapeutic effect in migraine is due to anti-inflammatory action. Ibudilast is a compound that inhibits "glial cell activation" in animal models and on this basis was investigated in a small pilot study for chronic migraine.[39] Ibudilast did not significantly reduce the frequency of migraine or affect a number of secondary endpoints. Ibudilast was also studied for medication-overuse headache in a small pilot study, and again had no significant benefit.[40]

In summary, there is animal and limited human evidence for a role for inflammation in migraine, but there is also significant evidence against it. Definitions of inflammation have undergone significant recent adaptations, and it is possible that there might, at some point, be selective inflammatory mechanisms within these new definitions that are clearly involved in migraine. It is important to recognize, however, that at present the hypothesis that inflammation plays a significant role in migraine remains just that: a hypothesis. At this stage, no definitive evidence supports the hypothesis that concepts and definitions of inflammation that have been developed for other disease states apply to migraine. Ongoing discussion about "inflammation" in migraine should involve consideration of the totality of the evidence, with specific definition of what is meant by the term in the context of a unique disease.

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