Illustration of neural pathways with a focus on GluA1 protein, symbolizing migraine pain relief.

Migraine Breakthrough: How Targeting a Specific Brain Protein Could End the Pain

Nico Varela in Health & Wellness November 2025 • 4 min read.

"New research identifies a key protein involved in migraine pain, offering hope for more effective treatments and relief for millions."

Migraines are more than just headaches; they are debilitating neurological conditions affecting millions worldwide. Characterized by intense throbbing pain, often accompanied by nausea, vomiting, and sensitivity to light and sound, migraines significantly impact quality of life. Understanding the complex mechanisms behind migraines is crucial to developing more effective treatments.

While various triggers and contributing factors have been identified, the precise molecular pathways that lead to migraine pain remain elusive. Current treatments often provide only partial relief and can come with undesirable side effects, highlighting the urgent need for new therapeutic targets.

Recent research has shed light on a promising new avenue for migraine treatment: targeting a specific protein in the brain. This discovery offers a potential breakthrough in how we understand and manage this widespread condition.

What Role Does GluA1 Play in Migraine Pain?

Illustration of neural pathways with a focus on GluA1 protein, symbolizing migraine pain relief.

A study published in "Neuropharmacology" has identified a critical role for the AMPA receptor GluA1 in nitroglycerin (NTG)-induced migraine-like pain. The research, conducted by Yuanyuan Tang, Sufang Liu, and colleagues, found that phosphorylation of GluA1 at a specific site (Ser831) is essential for the development of migraine-like pain in mice.

The study's findings suggest that when GluA1 is phosphorylated at Ser831, it contributes to the central sensitization of pain pathways, making the brain more sensitive to migraine triggers. This sensitization amplifies pain signals, leading to the intense discomfort experienced during a migraine attack.

The team discovered that injecting NTG, a known migraine trigger, increased GluA1 phosphorylation in the spinal trigeminal nucleus caudalis (Sp5C) of mice.
Mice with a mutated GluA1 gene (S831A), preventing phosphorylation, showed significantly less migraine-like pain after NTG injection.
The researchers also found that NTG triggers calcium influx in brainstem neurons, which is reduced by the GluA1 mutation.
Blocking calcium-permeable AMPA receptors in the Sp5C reduced migraine-like pain.

These results indicate that GluA1 phosphorylation at Ser831 is a crucial step in the development of NTG-induced migraine-like pain. By targeting this specific protein, researchers may be able to disrupt the pain pathway and provide more effective relief.

What Does This Mean for Migraine Treatment?

The identification of GluA1 as a key player in migraine pain opens up new possibilities for developing targeted therapies. By creating drugs that specifically inhibit GluA1 phosphorylation at Ser831, researchers hope to reduce the central sensitization that amplifies migraine pain. This targeted approach could potentially offer more effective relief with fewer side effects compared to current treatments. Further research is needed to translate these findings into clinical applications, but the discovery of GluA1's role in migraine pain represents a significant step forward in the quest for better migraine management.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1016/j.neuropharm.2018.02.026, Alternate LINK

Title: Ampa Receptor Glua1 Ser831 Phosphorylation Is Critical For Nitroglycerin-Induced Migraine-Like Pain

Subject: Cellular and Molecular Neuroscience

Journal: Neuropharmacology

Publisher: Elsevier BV

Authors: Yuanyuan Tang, Sufang Liu, Hui Shu, Ying Xing, Feng Tao

Published: 2018-05-01

Everything You Need To Know

What key protein has recent research identified as playing a critical role in migraine pain?

Recent research has pinpointed the AMPA receptor GluA1 as playing a critical role in migraine pain, specifically its phosphorylation at the Ser831 site. This phosphorylation is essential for the development of migraine-like pain. When GluA1 is phosphorylated, it contributes to the central sensitization of pain pathways, amplifying pain signals and leading to the intense discomfort experienced during a migraine attack.

How does GluA1 phosphorylation contribute to migraine development, according to the research?

The research indicates that GluA1 phosphorylation at Ser831 is a crucial step in the development of NTG-induced migraine-like pain. When nitroglycerin (NTG), a known migraine trigger, is introduced, it increases GluA1 phosphorylation in the spinal trigeminal nucleus caudalis (Sp5C). Blocking calcium-permeable AMPA receptors in the Sp5C reduced migraine-like pain.

What are the potential implications of identifying GluA1 as a key player in migraine pain for future treatment?

Targeting GluA1 phosphorylation at Ser831 opens possibilities for new migraine treatments. Drugs could be developed to inhibit this phosphorylation, reducing central sensitization and providing more effective relief with fewer side effects compared to current treatments. Further research is needed to translate these findings into clinical applications, but it's a promising step forward.

What methods were used in the "Neuropharmacology" study to determine the role of GluA1 in migraine pain?

The study in "Neuropharmacology" used mice to investigate nitroglycerin (NTG)-induced migraine-like pain. Researchers injected NTG into mice and observed increased GluA1 phosphorylation in the spinal trigeminal nucleus caudalis (Sp5C). Mice with a mutated GluA1 gene (S831A), preventing phosphorylation, showed significantly less migraine-like pain after NTG injection. This helped establish the link between GluA1 phosphorylation and migraine pain.

Can you explain the concept of central sensitization of pain pathways and how GluA1 relates to it in the context of migraines?

Central sensitization of pain pathways refers to the process where the brain becomes more sensitive to pain signals. In the context of migraines, GluA1 phosphorylation at Ser831 contributes to this sensitization, amplifying pain signals and leading to the intense discomfort experienced during a migraine attack. Understanding and targeting this sensitization could lead to more effective migraine treatments.