Patients want to know how the brain works and what causes their migraines. This is an important aspect of treatment and empowers them to take an active role.

They may have been referred to a headache specialist after several unsuccessful attempts at treatment. Typically, in this setting, patients have a high burden from their migraines, which they have suffered from for most of their adult lives. This combination can lead to frustration, hopelessness, and lack of trust. On top of this, there are broader issues such as medication overuse and healthcare costs. So, it is important to treat all migraine attacks and prevent them.^{1, 2}

Patients want to know how the brain works and what causes their migraines

Structural and chemical changes

In a healthy subject, the brain is able to habituate to a headache. But during a migraine attack, the brain loses the ability to habituate. This can happen in cycles, leading to episodic migraine, or constantly, causing chronic migraine.³ 

Neuroimaging reveals differences in the brain anatomy between episodic and chronic migraine. This is evident in cortical surface area and thickness⁴ in the hypothalamus,⁵ and in iron deposits.⁶

Changes in molecular biomarkers of inflammation in the periphery are also associated with chronic migraine.⁷ In women with episodic migraine, there is a slight increase in levels of calcitonin gene-related peptide (CGRP) and a further increase in CGRP in chronic migraine.⁸

Chronic migraine also has a characteristic epigenetic profile that research has started to identify. In a rat model, DNA methylation changed most in rats in a chronic migraine state.⁹ An mRNA expression analysis in human subjects showed that in chronic migraine, pro-inflammatory genes in the periosteum are activated and genes suppressing inflammation are deactivated.¹⁰ In another study, microRNA expression also differed between patients with chronic migraine and those with episodic migraine.

Chronification: modifiables and non-modifiables

When it comes to the change from episodic to chronic migraine, there are factors that can be actively changed by the patient (‘modifiables’) and factors that cannot be controlled (‘non-modifiables’). Modifiables include stress, obesity, and analgesic overuse. Examples of non-modifiables include age, sex, and race.¹¹

What do patients want to know?

Migraine patients want to find out about their brain and why they suffer migraines. These concepts can be presented to patients.

The lack of habituation is a key concept for patients to understand

Dr Pozo Rosich gave examples of what her patients want to know:

• Why me? There is a strong genetic component to migraine,¹² particularly in genes related to vascular and neuronal function. For example, the TRPM8 gene encodes a receptor for pain related to cold. It has a polymorphism common in Europeans but not in Africans, and this polymorphism contributes to a higher prevalence of migraine in Europeans.¹³
• Why like this? Migraines can occur when the brain is overloaded with too much information to process, which contributes especially to aura. The brain then needs to reset to a normal state through a process called cortical spreading depression: cortical activity increases, and then spontaneous and evoked activity decrease across the cortex. ¹⁴
• Why here? There are no pain receptors in the brain, but there are structures in the head that sense pain. The important areas for migraine are the dura and dural arteries. Migraine pain that feels like it is moving is usually referred pain from the periphery.
• Why so much? The amount and type of peripheral inflammation are critical. One of the most important and most treatable mediators is CGRP.⁵ There may also be differences in the periaqueductal gray matter, a brain region that would normally inhibit pain centrally.¹⁵ Allodynia (the sensitising of secondary neurons by repetitive stimuli) also plays a part, but moderate allodynia does not predict treatment efficacy.¹⁶
• Why now? The lack of habituation is a key concept for patients to understand. It gives context to a list of triggers and lifestyle changes that might not otherwise make sense to them.

Understanding the neurobiology of migraine helps patients engage with clinicians and lifestyle changes, especially if previous treatments were unsuccessful. This improves the chances of successfully managing their migraines.