We're delving into the intricate world of migraine pathophysiology and triggers, aiming to shed light on the pivotal role of calcitonin gene-related peptide, or CGRP, in understanding migraine headaches better. I have nothing to disclose. This micro-lecture has the following objectives. First, we will recognize headache triggers and identify common triggers associated with migraine attacks. Secondly, we will identify migraine phases and processes to understand the distinct phases of migraines better and recognize the physiological processes involved in each phase. Next, we will evaluate the significance of CGRP and assess its role in migraines. Lastly, we will link pathophysiology to treatment strategies and establish a clear connection between understanding migraine pathophysiology, particularly CGRP's role in migraine headaches and its application in selecting targeted treatments for migraine management. Many triggers associated with migraines relate to metabolic imbalances. Factors such as fasting, food triggers, disrupted sleep patterns, hormonal fluctuations, physical exertion, alcohol, and weather changes can all contribute to migraine headaches. Additionally, premonitory factors like sensitivity to light, often mistaken as a trigger, also play a role. When multiple triggers combine, they can reach a threshold, suggesting shared pathways in migraine onset. Psychological or physical stress, hormonal changes, and oxidative stress induced by such stressors can be triggering factors. Studies have revealed that 87.9% of individuals with migraines had identifiable triggering factors. Psychological stress emerged as a predominant trigger among these patients. Furthermore, environmental factors like high altitudes leading to hypoxia have been linked to increased migraine prevalence. Identifying these triggers becomes pivotal as we delve into the cyclical nature of migraines, comprehending the distinct phases within each attack. The migraine is a cyclical disorder marked by various symptoms during each headache attack. In its episodic form, it shows up with recurring stages. First comes a premonitory phase with signs like excessive yawning, thirst, sleepiness, food cravings, cognitive issues, and mood swing. Following this is the migraine aura, a brief period of neurological symptoms, often visual changes, just before the headache kicks in. Then, an intense headache hits, usually on one side of the head and worsened by movement, accompanied by heightened sensitivity to light and smells. Finally, there's the postdrome phase, bringing fatigue, trouble focusing, understanding, and stiffness in the neck. Migraine development involves central and peripheral triggers. Initially, the trigeminal ganglions first-order neuron receives signals from dural blood vessels, relaying it to the brainstem's second-order neuron and then to the third-order neuron in the thalamus. Dysthalamic neuron sensitization results in clinical extracranial hypersensitivity. Activation of the trigeminal ganglion leads to the release of CDRP and substance P, known triggers for inflammation and pain. No susceptive information travels from meningeal blood vessels to the trigeminal nucleus via C-type nerve fibers. In summary, the intricate mechanisms of central and peripheral sensitization, coupled with neurogenic inflammation and the release of key neuropeptides, unveil the complex journey of migraine development, shedding light on potential targets for effective intervention and management strategies. Migraine pathophysiology involves two key phases. During the early premonitory phase, the hypothalamic region is activated, while the headache phase sees activation of the trigeminal system. The biological process behind the migraine aura is believed to be cortical spreading depression. However, how the activation of the hypothalamus leads to cortical spreading depression and trigeminal system activation remains a mystery. It's possible that the hypothalamus triggers pathways involving other brain areas like the brainstem or the parasympathetic system. These pathways may contribute to the development of the migraine aura and the activation of the trigeminothalamic pathway. The pain patterns of migraine headaches resemble the referred pain observed after stimulating meningeal and cerebral arteries during brain surgery in awake patients. This pain's significance lies in its extensive innervation by trigeminal fibers. During migraine attacks, levels of CGRP are increased. Evidence from blood samples of patients or animal models with stimulated trigeminal fibers suggests that the CGRP found in migraine patients originates from the trigeminal nerve. CGRP acts as a potent dilator of blood vessels in the peripheral system and modulates no susceptive activity in the central system. Chemicals like CGRP and histamine, which typically do not cross the intact blood-brain barrier in migraine sufferers, can still trigger migraine attacks peripherally. Importantly, it's crucial to note that the origin of migraine pain isn't from dilation of blood vessels alone, as previously believed. Migraine headaches are not associated with cerebral or meningeal blood vessel dilation, suggesting that anti-migraine treatments may not necessarily need vasoconstrictor properties. Now that we understand the significance of CGRP levels in migraine, let's delve deeper into its impact and therapeutic relevance. Elevated CGRP levels are observed during both migraine attacks and interictal phases in migraine patients, remaining high for 48 to 72 hours post-headache and medication-free periods. However, there's a notable shift. CGRP levels show a reduction following both abortive and prophylactic treatments. This reduction is crucial, indicating a potential link between CGRP and migraine relief. What's fascinating is that CGRP itself has the ability to induce migraine-like headaches in individuals already experiencing migraine. This sheds light on the direct involvement of CGRP in the onset of migraine symptoms. The implications of these findings are significant in treatment development. Studies have demonstrated the effectiveness of CGRP antagonists and antibodies specifically targeting CGRP. These treatments show promise as abortive and prophylactic measures for managing migraines. This pivotal role of CGRP in both inducing migraines and as a target for successful treatments underscores its importance to understanding and potentially alleviating migraine symptoms. Thank you for listening.

migraine pathophysiology

CGRP

headache triggers

neurogenic inflammation

CGRP antagonists