Neuroscience/
Disease Overview
Delivering a Comprehensive Introduction for Improved Migraine Management
UNDERSTANDING MIGRAINE
The Role of CGRP: Key Modulator and Target in Migraine
Trigeminovascular System and Migraine
Migraine Is a Neurovascular Disorder
CGRP: Calcitonin gene-related peptide; TRPA1: Transient receptor potential cation channel ankyrin subfamily member 1; TRPV1: Transient receptor potential cation channel vanilloid subfamily member 1.
CGRP SIGNALING
Receptor/Ligand Binding
CGRP acts by binding to its receptor, which is found on the surface of a range of cell types, including vascular smooth muscle cells, neurons, glial cells, and mast cells.7
The CGRP receptor is a G-protein coupled receptor.
Binding of CGRP to its receptor leads to G-protein coupling and downstream signal activation.2,7
CGRP-Driven Signaling
CGRP: Calcitonin gene-related peptide; CLR: Calcitonin receptor-like receptor; GDP: Guanosine diphosphate; GPCR: G-protein coupled receptor; GTP: guanosine triphosphate; RAMP: Receptor activity-modifying protein.
CGRP AND MIGRAINE
Clinical studies have found elevated CGRP in the blood during migraine attack, making it an attractive therapeutic target.8
CGRP Levels in the Blood During Migraine vs Control.8
CGRP: Calcitonin-gene-related peptide.
NEUROTRANSMITTERS AND NEUROPEPTIDES ASSOCIATED WITH MIGRAINE
Release of neurotransmitters associated with neurovascular inflammation and sensitization.
CGRP: Calcitonin gene-related peptide; GABA: Gamma-aminobutyric acid; PACAP: Pituitary adenylate cyclase-activating polypeptide.
Summary
CGRP in the Body
CGRP plays a role in every major organ and system of the body via CGRP-containing nerve fibers.3
CGRP regulates the cardiovascular system, mediates neurogenic inflammation, and modulates nociceptive input.3
MIGRAINE DIAGNOSIS
Migraine can be classified as episodic or chronic depending on the frequency of attacks.12
ICHD-3 Diagnostic Criteria for Migraine12
Migraine is a debilitating, complex, and chronic disease characterized by frequent attacks with neurological and autonomic symptoms.13
Episodic migraine is more common than chronic migraine but can be as disabling.13
Frequency of migraine is fluctuant, and people can transition between chronic and episodic migraine.
Implications for clinical practice
- Diagnosis is intended to reflect a stable set of conditions, but migraine fluidity makes this difficult16
- Migraine pathophysiology is unlikely to change with the number of headache days16
- Consideration of factors, such as personal burden, is important to inform treatment choice17,18
*Risk factors associated with an increased risk of CM onset include headache features, depression, allergic rhinitis, asthma, and poor acute treatment optimization.
Challenges associated with diagnosing chronic migraine.
CGRP: Calcitonin gene-related peptide; ICHD-3: International Classification of Headache Disorders; CM: Chronic migraine; EM: Episodic migraine.
References
1. Raddant A and Russo AF. Expert Rev Mol Med. 2011;13:e36.
2. Edvinsson L. BJ Clin Pharmacol. 2015;80:193–9.
3. Russo AF. Ann Rev Pharmacol Toxicol. 2015;55:533–52.
4. Goadsby PJ, et al. Physiol Rev. 2017;97:553–622.
5. Aurora SK, et al. Headache. 2017;57(1):109-125.
6. Ferrari MD, et al. Nat Rev Dis Primers. 2022;8(1):2.
7. Bell I. J Med Chem 2014;57:7838–58.
8. Goadsby PJ, et al. Ann Neurol. 1990;28:183–7.
9. Malhotra R. Ann Indian Acad Neurol. 2016;19(2):175-182.
10. Edvinsson L, et al. J Headache Pain. 2018;19(1):21.
11. Park CG, et al. Sci Rep. 2022;12(1):6921.
12. Headache Classification Committee of the International Headache Society (IHS). Cephalalgia 2018;38:1–211.
13. Ferrari MD, et al. Nat Rev Dis Primers. 2022;8(1):2.
14. Buse DC, et al. Headache. 2019;59:1286–99.
15. Chalmer MA, et al. Cephalgia. 2019;40:399–406.
16. Serrano D, et al. J Headache Pain. 2017;18:101.
17. Ever S, et al. Eur J Neurol. 2009;16:968–81.
18. Ailani J, et al. Headache. 2021;61:1021–39.
19. Becker WJ, et al. Headache. 2017;57(9):1471–1481.
20. https://migrainebuddy.com/migraine/migrainesymptoms-the-stages-of-a-migraine. Accessed January 22, 2021.