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Calcitonin gene related peptide (CGRP) is a member of the calcitonin family of peptides, which in humans exists in two forms, α-CGRP and β-CGRP. α-CGRP is a 37 amino acid peptide and is formed from the alternative splicing of the calcitonin/CGRP gene located on chromosome 11. CGRP is one of the most abundant peptides produced in both peripheral and central neurons.  It is the most potent peptide vasodilator and can function in the transmission of pain. In the trigeminal vascular system the cell bodies on the [trigeminal ganglion] are the main source of CGRP. CGRP is thought to play a role in cardiovascular homeostasis and nociception. CGRP mediates its effects though a heteromeric receptor composed of a G protein-coupled receptor called calcitonin receptor-like receptor (CLR) and a receptor activity-modifying protein (RAMP1) . CGRP receptors are found throughout the body suggesting that the protein may modulate a variety of physiological functions in all major systems (eg, respiratory , endocrine , gastrointestinal, immune, and cardiovascular) . Increased levels of CGRP have been reported in migraine and Temporomandibular joint disorder patients as well as a variety of other diseases such as cardiac failure, hypertension, and sepsis 
Regulation of the calcitonin gene related peptide (CGRP) gene is in part controlled by the expression of the mitogen-activated protein kinases (MAPK) signaling pathway,cytokines such as TNFα  and iNOS  . 5HT1 agonists such as sumatriptan increase intracellular calcium which cause decreases in CGRP promoter activity. Botulinum toxin type A is able to prevent stimulated release of CGRP through the cleavage of SNAP-25 protein. Receptor antagonists such as telcagepant, which is in phase III from Merck Pharmaceuticals, also has promise in limiting the effects of CGRP .
The Role of CGRP in headache
Preclinical evidence suggests that during a migraine, activated primary sensory neurons (meningeal nociceptors) in the trigeminal ganglion release CGRP from their peripherally projecting nerve endings located within the meninges. This CGRP then binds to and activates CGRP receptors located around meningeal vessels causing vasodilation, mast cell degranulation and plasma extravasation. Human observations have further implicated the role of CGRP in the pathophysiology of migraine. Activation of primary sensory neurons in the trigeminal vascular system in humans can cause the release of CGRP. During some migraine attacks increased concentrations of CGRP can be found in both saliva and plasma drawn from the external jugular vein. Furthermore intravenous administration of alpha-CGRP is able to induce headache in individuals susceptible to migraine.
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