Triptans and CGRP blockade – impact on the cranial vasculature

Abstract

The trigeminovascular system plays a key role in the pathophysiology of migraine. The activation of the trigeminovascular system causes release of various neurotransmitters and neuropeptides, including serotonin and calcitonin gene-related peptide (CGRP), which modulate pain transmission and vascular tone. Thirty years after discovery of agonists for serotonin 5-HT1B and 5-HT1D receptors (triptans) and less than fifteen after the proof of concept of the gepant class of CGRP receptor antagonists, we are still a long way from understanding their precise site and mode of action in migraine. The effect on cranial vasculature is relevant, because all specific anti-migraine drugs and migraine pharmacological triggers may act in perivascular space. This review reports the effects of triptans and CGRP blocking molecules on cranial vasculature in humans, focusing on their specific relevance to migraine treatment.

Pathophysiology of chronic pain in cerebral palsy: implications for pharmacological treatment and research

“…Several small‐molecule CGRP receptor antagonists have been developed for treatment of acute migraine attacks and CGRP antibodies for migraine prevention. Both approaches have shown efficacy in clinical trials, but the receptor antagonists have been discontinued owing to liver toxicity . Intriguingly, CGRP levels in plasma, synovial, and cerebrospinal fluid and tissue biopsies are elevated and correlated to pain in individuals with degenerative disc disease and osteoarthritis .…”

“…Both approaches have shown efficacy in clinical trials, but the receptor antagonists have been discontinued owing to liver toxicity. 57 Intriguingly, CGRP levels in plasma, synovial, and cerebrospinal fluid and tissue biopsies are elevated and correlated to pain in individuals with degenerative disc disease and osteoarthritis. 58 Thus, it has been proposed that CGRP may be a critical factor also in non-migraine pain, but this remains to be defined.…”

Triptans for Migraine Patients With Vascular Risks: New Insights, New Options

“…In the young female population, however, the absolute risk of stroke is quite low, and even in those with OC use and MWA, 23 out of 10,000 will suffer a stroke over a period of 10 years. 47 In a study of 26 women suffering from typically unilateral MWoA, cilostazol-induced attacks were studied with 3 Tesla magnetic resonance angiography. [38][39][40][41] The risk associated with low and very low dose estrogencontaining OCs may be minimal or even absent, and arguments have been made that contra-indication to the use of OCs containing 20 mcg or less of ethinyl estradiol in patients with MWA is unwarranted.…”

“…77 Their therapeutic gain seems to be lower than that of the triptans and their cost is still to be determined, but their presumably lower risk of producing vascular complications will undoubtedly support their use in practice. 47 As CGRP does play a role in vasoregulation, especially in sub-ischemic settings, one plausibly could theorize that a patient with vascular risk factors using a triptan may be more at risk for cardiac or cerebral ischemia with an anti-CGRP MAB than without. 79 Neuromodulation approaches and gepants could be used without concern regarding the risk of inducing medication overuse headache, as both potentially may exert a preventive effect if used frequently.…”

Antigens and Antibodies in Disease With Specifics About CGRP Immunology

“…The neuropeptide CGRP is firmly established as a biomarker for migraine and a key neurotransmitter in migraine pathophysiology. CGRP is a potent vasodilator expressed and released in the perivascular space by trigeminal sensory neurons with a central role in neurogenic inflammation . An additional summary list of abbreviated details of CGRP in migraine includes: CGRP + nerves innervate all pertinent cerebral arteries; released into the jugular venous system during migraine; ictal migraine and inter‐ictal chronic migraine levels are elevated; infusion evokes migraine‐like attacks; levels are reduced in parallel with triptan efficacy; all novel selective antagonists are effective …”