What Does CGRP Stand For?
Calcitonin gene-related peptide (CGRP) is a neuropeptide (neurotransmitter of the nervous system) discovered over 30 years ago. It has specific receptors located both centrally and in the periphery. CGRP is present in trigeminal neurons and is released into the cranial venous outflow in acute migraine and cluster headache attacks (1).
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CGRP has several functions (2), such as:
- Contributes to gastric acid secretion
- Temperature homeostasis
- Increases heart rate
- Plays a role in the release of the pituitary hormones
- Highly potent vasodilator with protective mechanisms
- Wound healing
CGRP is primarily released from sensory nerves and thus is implicated in pain. Increased levels of CGRP have been reported in migraines, cluster headaches, and might as well be present in temporomandibular disorders (3).
Within the brain, CGRP increases with ischemia, injury, hyperthermia, and seizures, activating neuroprotective processes (4).
The role of CGRP in pain management is likely mediated by modulating nociception and sustaining neurogenic inflammation that leads to peripheral and central pain sensitization (for example in migraine) (5).
CGRP as a Target For Pain Management
The use of monoclonal antibodies against CGRP is a novel therapeutic strategy for the management of some painful conditions, such as migraine and cluster headache (6).
CGRP-related therapies were designed specifically to act on the trigeminal pain system, with little or no adverse effects. Two groups of medications are available.
- Small molecule CGRP receptor antagonists (gepants) for acute relief of migraine headache
- Monoclonal antibodies against CGRP (Eptinezumab, Fremanezumab, and Galcanezumab) or the CGRP receptor (Erenumab) to prevent migraine attacks (7).
Considering the comorbidity between migraine and TMD and the role of CGRP in the trigeminal pain system, CGRP receptor antagonists may have therapeutic efficacy in the treatment of other facial pain conditions. Understanding the pain mechanisms offers opportunities to develop therapeutic strategies with better chances to improve patient’s wellbeing (8).
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- Edvinsson L. The Trigeminovascular Pathway: Role of CGRP and CGRP Receptors in Migraine. Headache. 2017 May; 57 Suppl 2:47-55. doi: 10.1111/head.13081. PMID: 28485848.
- Russell, F. A., King, R., Smillie, S. J., Kodji, X., & Brain, S. D. (2014). Calcitonin gene-related peptide: physiology and pathophysiology. Physiological reviews, 94(4), 1099–1142.
- Yuan H, Spare NM, Silberstein SD. Targeting CGRP for the Prevention of Migraine and Cluster Headache: A Narrative Review. Headache. 2019 Jul; 59 Suppl 2:20-32. doi: 10.1111/head.13583. PMID: 31291020.
- Borkum, JM. CGRP and Brain Functioning: Cautions for Migraine Treatment. Headache. 2019 Sep; 59(8): 1339-1357. doi: 10.1111/head.13591. Epub 2019 Jul 21. PMID: 31328279.
- Yuan H, Lauritsen CG, Kaiser EA, Silberstein SD. CGRP Monoclonal Antibodies for Migraine: Rationale and Progress. BioDrugs. 2017 Dec;31(6):487-501. doi: 10.1007/s40259-017-0250-5. PMID: 29116598.
- Carmine Belin A, Ran C, Edvinsson L. Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache. Brain Sci. 2020 Jan 6;10(1): 30. doi: 10.3390/brainsci10010030. PMID: 31935868; PMCID: PMC7016902.
- Akerman S, Romero-Reyes M. Preclinical studies investigating the neural mechanisms involved in the co-morbidity of migraine and temporomandibular disorders: the role of CGRP. Br J Pharmacol. 2020 Dec; 177(24): 5555-5568. doi: 10.1111/bph. 15263. Epub 2020 Oct 21. PMID: 32929719; PMCID: PMC7707098.
- Edvinsson L. Role of CGRP in Migraine. Handb Exp Pharmacol. 2019; 255: 121-130. doi: 10.1007/164_2018_201. PMID: 30725283.
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