Fresh understanding of the causes of migraine reveals new drug targets
New Scientist
February 20, 2026
AI-Generated Deep Dive Summary
A new study is shedding light on the role of substance P, a chemical messenger linked to migraines, after decades of being overlooked as a potential drug target. Researchers have found that substance P plays a significant role in triggering migraine symptoms, including blood vessel dilation and inflammation, which contribute to pain and discomfort.
The trigeminal nerve has long been implicated in migraines, and substance P is released by this nerve. Previous attempts to develop drugs targeting substance P's neurokinin-1 receptor (NK1-R) failed in the late 1990s, leading researchers to abandon this pathway. However, recent findings reveal that substance P also binds to MRGPRX2 receptors, causing inflammation and amplifying pain signals. This discovery suggests that earlier drug failures may have been due to targeting only one receptor type.
New advancements in monoclonal antibody technology are now allowing scientists to explore blocking substance P more effectively. These antibodies can directly target molecules like CGRP or PACAP, which are already known migraine-related neuropeptides. For example, Lundbeck's anti-PACAP drug, bocunebart, has shown promise in reducing monthly migraine days, according to early trial results.
This shift in focus could lead to more effective treatments for migraines, particularly for the 1 in 3 patients who don't respond to current therapies like CGRP inhibitors. By revisiting substance P and other neuropeptides, researchers hope to develop a new wave of targeted migraine treatments that address the condition's complex mechanisms.
This research not only deepens our understanding of migraines but also highlights the importance of re-evaluating previously dismissed pathways. As scientists continue to uncover the underlying causes of migraines, they are paving the way for innovative therapies that could transform how we manage this debilitating condition.
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Originally published on New Scientist on 2/20/2026