Modulators of Migraine Pain: Discovering the Role of Excitatory and Inhibitory Neurotransmitters in the Brain
An important observation from our migraine provocation studies is that only people with migraine develop migraine attacks, whereas healthy volunteers develop mild or no headache.4 This raises a critical question: Which neurotransmitters (and metabolites) alter activation thresholds of pain-sensing nerve cells in the migraine brain? Alternatively, how might these transmitters modulate the perception of migraine pain during attacks? Understanding these dynamics is essential for deciphering the mechanisms that initiate and terminate migraine attacks, as well as its recurrent nature. To bridge this knowledge gap, we will use functional magnetic resonance spectroscopy (fMRS). This allows for real-time detection and monitoring of neurotransmitters, such as glutamate (which excites nerve cells) and GABA (which inhibits nerve cells).
The use of fMRS will enable us to observe neurotransmitter changes in the brain during sensory processing tasks, such as visual stimulation, and during pathological conditions, such as a migraine attack. Furthermore, by comparing the neurotransmitter levels of people with migraine to those with tension-type headache (TTH), lower back pain, and healthy controls, we intend to delineate the unique neurobiological features that set migraine apart from other pain disorders.
Sub-projects exploring migraine modulators
Sub-Project 3: Population-Based Comparison of Metabolic and Functional Alterations in Migraine, TTH, Lower Back Pain, and Healthy Controls using fMRS.
Objective:
To identify specific metabolic and functional alterations associated with migraine and distinct from TTH, lower back pain, and healthy individuals.
Potential Significance:
This sub-project will reveal unique alterations in neurotransmitters levels and neuronal activity that are specific to migraine. Our findings will thus advance our current pathophysiological understanding and possibly identify a molecular signature specific to migraine.
Sub-Project 4: Investigating the Initiation and Termination of Migraine Attacks using fMRS
Objective:
To investigate neurochemical alterations associated with the initiation and termination of spontaneous migraine attacks.
Potential Significance:
Mapping neurochemical and functional alterations throughout different phases of the migraine cycle will uncover the basic mechanisms that predispose to, initiate, and eventually terminate attacks. Our team’s future endeavors will then involve using molecular migraine triggers to manipulate and observe these fundamental mechanisms during the initiation and termination of provoked migraine attacks.