Sumatriptan Causes Parallel Decrease in Plasma Calcitonin Gene-Related Peptide (CGRP) Concentration and Migraine Headache During Nitroglycerin Induced Migraine Attack

Abstract

Sumatriptan-induced changes in plasma calcitonin gene-related peptide (CGRP) concentration and headache intensity were investigated in 19 female migraineurs during nitroglycerin-induced migraine attack. Sumatriptan nasal spray was administered 120 min after the onset of the attack. Blood samples were obtained immediately before and 60 min after sumatriptan administration. In those subjects whose migraine attack improved considerably 60 min after the treatment the plasma CGRP concentration decreased significantly (P<0.05). In contrast, plasma CGRP concentration failed to change in patients whose headache did not improve. In addition, plasma CGRP concentrations showed significant positive correlations with the headache scores both 60 and 120 min after sumatriptan administration (P<0.05). According to our results plasma CGRP concentration decreases parallel to headache intensity during sumatriptan treatment and this decrease in CGRP predicts effectiveness of antimigraine drug therapy. This supports that one of the main effects of triptans is to decrease CGRP release.

CGRP Receptor Antagonism and Migraine

“…62,63 In addition, nitroglycerine did not elicit cluster headache attacks if the patient was not in a prone status (i.e., a state in which the disease was active and a small stimulation could then elicit the full cluster headache attack). Studies of the perfused middle cerebral artery 4,61,64 showed that CGRP does not readily pass the blood-brain barrier, which agrees well with this supposition; the nerve fibers are situated in the adventitia and act on the receptors located in the smooth muscle cells. Thus, a low degree of perivascular CGRP release likely occurs in mild to mod-erate attacks, but it is necessary to have a large release to measure the peptide in the cranial venous effluent.…”

“…66,67 In addition, after sumatriptan or rizatriptan administration, the plasma levels of CGRP returned to control levels, with successful amelioration of the headache. 4,61,64 These results have been confirmed in experimental studies using zolmitriptan, rizatriptan, sumatriptan, and dihydroergotamine. The 5-HT 1B/1D receptors are expressed on human trigeminal ganglion cells and on trigeminal sensory fibers, 68 thus providing sites for presynaptic inhibition of the CGRP release and of contractile 5-HT 1B receptors in intracranial arteries.…”

“…60 Further experiments have provided supportive data demonstrating a linear correlation between the increased levels of CGRP and the intensity of the headache. 61,62 It is worth noting that low pain results in no significant increase in venous CGRP. 62,63 In addition, nitroglycerine did not elicit cluster headache attacks if the patient was not in a prone status (i.e., a state in which the disease was active and a small stimulation could then elicit the full cluster headache attack).…”

Control of the Calcitonin Gene-related Peptide Enhancer by Upstream Stimulatory Factor in Trigeminal Ganglion Neurons

“…Most notably, systemic administration of CGRP induces migraine-like symptoms among migraineurs (7), and a CGRP receptor antagonist can attenuate migraine (8). The possibility that CGRP synthesis is elevated during migraine is suggested by elevation of serum CGRP levels during spontaneous migraine (9,10). Given the generally long duration of migraine, it seems reasonable that these elevated CGRP levels might be sustained by increased transcription.…”

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

“…A correlation was detected between the CGRP level, the timing of the attack and the severity of the pain. The influence of CGRP in migraine headache is validated by the administration of triptans, which successfully ameliorate the attacks, the level of CGRP returning to the control [19].…”