Migraine pathophysiology involves complex interactions between neurological, vascular, and neurochemical systems. Key contributors include neurotransmitters and neuropeptides such as serotonin, dopamine, norepinephrine, and calcitonin gene-related peptide (CGRP).1 Each of these play distinct roles in the initiation and the persistence of migraines. This multifactorial nature explains why different therapeutic approaches may be effective for individual patients.2,3
The trigeminovascular theory highlights how neuropeptides like CGRP mediate neurovascular coupling during migraine attacks.1 CGRP, synthesized in trigeminal ganglion neurons, binds to heterodimeric receptors (CLR/RAMP1) triggering downstream signaling cascades.4 Although GCRP’s role in migraine pathogenesis is well established, the precise receptor mechanisms underlying its effects are not always clear.4 Additionally, other pathways involving glutamate, GABA, and inflammatory mediators also contribute significantly to migraine pathogenesis.4
Current preventive strategies target diverse mechanisms: anticonvulsant drugs modulate neuronal excitability, beta-blockers affect cardiovascular responses, ditans act as 5-HT1F receptor agonists to influence trigeminal signaling, and newer biologic agents target specific neuropeptide pathways.5 Four anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) represent one targeted approach among multiple therapeutic options.6
In pediatric populations, treatment selection involves balancing efficacy, safety profiles, and developmental considerations across all available options. Different mechanisms may be optimal for different patients based on individual migraine characteristics, comorbidities, and response patterns.2,3
Recent pharmacokinetic studies across various preventive agents inform age-appropriate dosing strategies.2,3,5 With an expanding array of available therapies, clinicians can create a more personalized approach to migraine management. Understanding diverse pathophysiological pathways supports precision medicine approaches, matching individual patients with optimal therapeutic mechanisms.
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