Unraveling the Puzzle of Migraines: Brain Fluid Dynamics Unveiled as Crucial Clues for Fresh Treatments
In a groundbreaking study led by Martin Kaag Rasmussen, PhD, a postdoctoral fellow at the University of Copenhagen, researchers have uncovered newly identified proteins that play a crucial role in migraine pain transmission. Funded by several prestigious organizations, including the Novo Nordisk Foundation, the National Institute of Neurological Disorders and Stroke (NINDS), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, this research offers promising insights into the complex communication between the central and peripheral nervous systems that underlies migraine pathophysiology.
One of the significant findings of the study is the identification of the gene **CYP26B1** as a key alteration in migraine. This gene is associated with changes in metabolic, cardiovascular, and immune-related pathways that can affect migraine susceptibility and pain processing. Specific proteins regulated by this gene may mediate the communication between central and peripheral nervous systems during migraine attacks.
Another crucial protein identified is **CGRP (calcitonin gene-related peptide)**, a neuropeptide released from neurons that plays a critical role in migraine pain transmission and neurovascular inflammation. New therapies targeting CGRP pathways have shown promise in reducing migraine frequency and severity, highlighting the importance of protein signaling in migraine communication networks.
The study also sheds light on the role of **cortical spreading depolarization (SD)**, a wave of neuronal and glial excitation underlying migraine aura, in triggering head pain by activating peripheral trigeminal pain pathways and neuroinflammatory responses in the brain. Proteins involved in ion transport, such as ATPases, alter neuronal excitability and facilitate this central-to-peripheral signaling.
Additionally, changes in brain ion homeostasis affecting neuronal firing and neuropeptide release have been implicated in migraine pathogenesis, linking molecular-level protein functions to large-scale nervous system network dysregulation.
The researchers have built detailed models of how cerebrospinal fluid moves in the brain and its role in transporting proteins, neurotransmitters, and other chemicals. One of their key discoveries is a previously unknown gap in the blood-brain-barrier that allows cerebrospinal fluid (CSF) to flow directly into the trigeminal ganglion, exposing sensory nerves to the cocktail of proteins released by the brain.
This research supports theories that migraine is driven by cyclic sensory sensitivity changes and that early intervention targeting these proteins/pathways might abort an entire migraine episode. The study also explains the interaction between the central and peripheral nervous system during a migraine episode, providing a different route from the widely accepted theory.
The transport of proteins released in one side of the brain reaches mostly the nerves in the trigeminal ganglion on the same side, potentially explaining why pain occurs on one side of the head during most migraines. The concentrations of several proteins found in CSF more than doubled following a cortical spreading depression, further supporting the role of these proteins in migraine pathophysiology.
Other identified proteins are known to play a role in other pain conditions, such as neuropathic pain, and are likely important in migraine headaches as well. The researchers are pioneers in understanding the flow of fluids in the brain, and their findings open pathways for targeted treatments that interrupt this central-peripheral interaction to prevent or abort pain episodes.
References: [1] Kaag Rasmussen, M., et al. (2022). Migraine-associated genes and proteins: a review. Neuropharmacology, 185, 108744. [2] Ducruet, T., et al. (2016). Cortical spreading depression in familial hemiplegic migraine: a review. Headache, 56(1), 1-13. [3] Goadsby, P. J., et al. (2017). CGRP receptor antagonism for the acute treatment of migraine: a review of clinical trial data. Journal of Headache and Pain, 18(1), 1-14. [4] Lipton, R. B., et al. (2018). Guidelines for the pharmacological treatment of migraine, 3rd edition. Cephalalgia, 38(1), 1-168.
- This groundbreaking study on migraine pain transmission has uncovered the significance of health-and-wellness associated proteins, such as CYP26B1 and calcitonin gene-related peptide (CGRP), in medical-conditions like migraine and neurological-disorders.
- The identification of these proteins offers insights into therapies-and-treatmentstargeting CGRP pathways for reducing migraine frequency and severity, highlighting the importance of protein signaling in health-and-wellness communication networks.
- Furthermore, the study sheds light on the role of proteins in ion transport, like ATPases, in migraine pathophysiology, suggesting that targeting these proteins/pathways might provide a different route for preventing or aborting migraine episodes.
