Top

Published in:

Open Access 01-06-2009 | Review Article

Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? A review

Authors: Peer Tfelt-Hansen, Han Le

Published in: The Journal of Headache and Pain | Issue 3/2009

Abstract

The involvement of calcitonin gene-related peptide (CGRP) in migraine pathophysiological mechanisms is shown by the facts that CGRP can induce migraine and that two CGRP antagonists, olcegepant and telcagepant, are effective in the treatment of migraine attacks. Increase of the neuropeptide CGRP during migraine and cluster headache attacks in the extracerebral circulation as measured in the external jugular vein (EJV) has been regarded as an established fact. Then in 2005, a study, using the migraine patients as their own controls, showed; however, no changes of CGRP in EJV. For migraine there is thus some uncertainty as to whether CGRP is increased in all migraine patients and more research is needed. In contrast, there are three ‘positive’ studies in cluster headache in which both sumatriptan, O₂ and spontaneous resolution normalized CGRP. The source of an increase of CGRP in EJV is most likely a ‘nervous vasodilatory drive’ in the extracranial vascular bed. It remains an enigma how the observed increase of CGRP in the EJV fits into the mechanisms of migraine and cluster headache.

Lassen LH, Tfelt-Hansen P, Jacobsen VB, Haderslev PA, Sperling B, Iversen HK, Olesen J (2008) The effect of intravenous infusion of human calcitonin gene-related peptide on middle cerebral artery and cerebral blood flow in migraine patients. J Headache Pain 9:151–157PubMedCentralPubMedCrossRef

Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier et al (2004) BIBN 4096 BS Clinical Proof of Concept Study Group Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Eng J Med 350:1104–1110

Ho TW, Mannix LK, Fan X, Assaid C, Furtek C, Jones CJ et al (2008) Randomized controlled trial of an horal CGRP antagonist, MK-0974, in acute treatment of migraine. Neurology 70:1304–1312PubMedCrossRef

Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X et al (2008) Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet 372:2115–2125PubMedCrossRef

Amara SG, Jonas V, Rosenfeld MG, Ong ES, Evans RM (1982) Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature 298:240–242PubMedCrossRef

Brain SD, Cambridge H (1996) Calcitonin gene-related peptide: vasoactive effects and potential therapeutic role. Gen Pharmacol 1996(27):607–611CrossRef

Sexton PM (1991) Central nervous binding sites for calcitonin and calcitonin gene-related peptide. Mol Neurobiol 5:251–273PubMedCrossRef

Edvinsson L, Goadsby PJ (1995) Neuropeptides in the cerebral circulation: relevance to migraine. Cephalalgia 15:272–276PubMedCrossRef

Edvinsson L (1985) Functional role of perivascular peptides in the control of the cerebral circulation. Trends Neurosci 9:126–131CrossRef

10.

Uddman R, Edvinsson L, Ekman R, Kingman T, McCulloch J (1985) Innervation of the feline cerebral vasculature by nerve fibers containing calcitonin gene-related peptide: trigeminal origin and co-existence with substance P. Neurosci Lett 62:131–136PubMedCrossRef

11.

Ponyer DR (1992) Calcitonin gene-related peptide: multiple actions, multiple receptors. Pharmacol Ther 56:23–51CrossRef

12.

Hill RG, Oliver KR (2007) Neuropeptide and kinin antagonists. Handb Exp Pharmacol 177:181–216

13.

van Rossum D, Hanisch UK, Quirion R (1997) Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev 21:649–678PubMedCrossRef

14.

Powell KJ, Ma W, Sutak M, Doods H, Quirion R, Jhamandas K (2000) Blockade and reversal of spinal morphine tolerance by peptide and non-peptide calcitonin gene-related peptide receptor antagonists. Br J Pharmacol 131:875–884PubMedCentralPubMedCrossRef

15.

Wimalawansa SJ (1996) Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocr Rev 17:533–585PubMedCrossRef

16.

Arulmani U, MaasenVanDenBrink A, Villalon CM, Saxena PR (2004) Calcitonin gene-related peptide and its role in migraine pathophysiology. Eur J Pharmacol 500:315–330PubMedCrossRef

17.

Goadsby PJ, Edvinsson L, Ekman R (1990) Vasoactive peptide release in the extracerebral circulation of humans during migraine attacks. Ann Neurol 28:183–187PubMedCrossRef

18.

Goadsby PJ, Edvinsson L (1993) The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 33:48–56PubMedCrossRef

19.

Goadsby PJ, Edvinsson L (1994) Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attack therapies. Brain 117:427–434PubMedCrossRef

20.

Fanciullacci M, Alessandri M, Figini M, Geppetti P, Michelacci S (1995) Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitro-glycerin-induced cluster headache attack. Pain 60:119–123PubMedCrossRef

21.

Fanciullacci M, Alessandri M, Sicuteri R, Marabini S (1997) Responsiveness of the trigeminovascular system to nitroglycerin in cluster headache patients. Brain 120:283–288PubMedCrossRef

22.

Tvedskov JF, Lipka K, Ashina M, Iversen HK, Schifter S, Olesen J (2005) No increase of calcitonin gene-related peptide in jugular blood during migraine. Ann Neurol 58:561–563PubMedCrossRef

23.

Schifter S (1991) Circulating concentrations of calcitonin gene-related peptide (CGRP) in normal man determined with a new, highly sensitive radioimmunoassay. Peptides 12:365–369PubMedCrossRef

24.

Goadsby PJ (2008) Calcitonin gene-related peptide (CGRP) antagonists and migraine: is it a new area? Neurology 70:1300–1301PubMedCrossRef

25.

Colonna DM, Meng W, Deal DD, Busija DW (1994) Calcitonin gene-related peptide promotes cerebrovascular dilation during cortical spreading depression in rabbits. Am J Physiol 266:H1095–H1102PubMed

26.

Wahl M, Schilling L, Parsons AA, Kaumam A (1994) Involvement of calcitonin gene-related peptide and nitric oxide (NO) in pial artery dilatation elicited by cortical spreading depression. Brain Res 637:204–210PubMedCrossRef

27.

Piper RD, Edvinsson L, Ekman R, Lambert GA (1993) Cortical spreading depression does not result in the release of calcitonin gene-related peptide into the external jugular vein of the cat: relevance to human migraine. Cephalalgia 13:180–183PubMedCrossRef

28.

Davis DD, Story HE (1943) Carotid circulation in the domestic cat. Publications of Field Museum of Nathional History 28:5–47

29.

Edvinsson L, Nilsson E, Jansen-Olesen I (2007) Inhibitory effect of BIBN4096BS, CGRP(8–37), a CGRP antibody and an RNA-Spigelmer on CGRP induced vasodilatation in the perfused and non-perfused rat middle cerebral artery. Br J Pharmacol 150:633–640PubMedCentralPubMedCrossRef

30.

Edvinsson L, Tfelt-Hansen P (2008) The blood–brain barrier in migraine treatment. Cephalalgia 28:1245–1258PubMedCrossRef

31.

Goadsby PJ, Edvinsson L, Ekman R (1988) Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 23:193–196PubMedCrossRef

32.

Goadsby PJ, Duckworth JW (1987) Effect of stimulation of trigeminal ganglion on cerebral blood flow in cats. Am J Physiol 253:R270–R274PubMed

33.

Goadsby PJ, Lambert GA, Lance JW (1986) Stimulation of trgigeminal ganglion increases flow in the extracerebral but not the cerebral circulation of the monkey. Brain Res 381:63–67PubMedCrossRef

34.

Escott KJ, Beattie DT, Connor HE, Brain SD (1995) Trigeminal ganglion stimulation increases facial skin blood flow in the rat: a major role for calcitonin gene-related peptide. Brain Res 669:93–99PubMedCrossRef

35.

Limmroth V, Katsarava Z, Liendent B, Schmitz K, Diener HC, Michel MC (2001) An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system. Pain 92:101–106PubMedCrossRef

36.

Zagami AS, Goadsby PJ, Edvinsson L (1990) Stimulation of the superior sagital sinus in the rat causes release of vasoactive peptides. Neuropeptides 16:69–75PubMedCrossRef

37.

Knight E, Edvinsson L, Goadsby PJ (2001) 4991W93 inhibits release of calcitonin gene-related peptide in the cat but only in doses with 5HT(1B/1D) receptor agonist activity. Neuropharmacology 40:520–525PubMedCrossRef

38.

Offenhauser N, Zinck T, Hoffmann J, Schiemann K, Schuh-Hofer S, Rohde W, Arnold G, Dirnagl U, Jansen-Olesen I, Reuter U (2005) CGRP release and c-fos expression within trigeminal nucleus caudalis of the rat following glyceryltrinitrate infusion. Cephalagia 25:225–236CrossRef

39.

Headache Classification Committee of the International Headache Society (2004) Classification and diagnostic criteria for headache disorders, cranial neuralgia and facial pain. Cephalalgia 24 (suppl 1):9–160

40.

Durham PL, Russo AF (1999) Regulation of calcitonin gene-related peptide secretion by serotonergic antimigraine drugs. J Neurosci 19:3423–3429PubMed

41.

Hansen JM, Petersen J, Wienecke T, Olsen KS, Jensen LT, Ashina M (2008) Sumatriptan does no change calcitonin gene-related peptide in the cephalic and extracephalic circulation in healthy volunteers. Abstract book. European Headache and Migraine nTrust International Congress, p 46

42.

Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ, Frackowiak RS et al (2005) A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Brain 128:932–939PubMedCrossRef

43.

Thomsen L, Kruuse C, Iversen H, Olesen J (1994) A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks. Eur J Neurol 1:73–80PubMedCrossRef

44.

Gallai V, Sarchielli P, Floridi A, Franceschini M, Codini M, Trequattrini A, Palumbo R (1995) Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both ictally and interictally. Cephalalgia 15:384–390PubMedCrossRef

45.

Ghatei MA, Stratton MR, Allen JM, Joplin GF, Polak JM, Bloom SR (1987) Co-secretion of calcitonin gene-related peptide, gastrin-releasing peptide and ACTH by a carcinoid tumour metastasazing to the cerebellum. Postgrad Med J 63:123–130PubMedCentralPubMedCrossRef

46.

Schon F, Thomas DT, Jewkes DA, Ghatei M, Mulderry PK, Bloom SR (1987) Failure to detect plasma neuropeptide release during trigeminal thermocoagulation. J Neurol Neurosurg Psychiatr 50:642–643PubMedCentralPubMedCrossRef

47.

Juhasz G, Zsombok T, Modos EA, Olajos S, Jakab B, Nemeth J et al (2003) No-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release. Pain 106:461–470PubMedCrossRef

48.

Juhasz G, Zsombok T, Jakab B, Nemeth J, Szolesanyri J, Bagdy G (2005) Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced attack. Cephalalalgia 25:179–183CrossRef

49.

Ashina M, Bendtsen L, Jensen R, Schifter S, Olesen J (2001) Calcitonin gene-related peptide during nitric-oxide headache in patients with chronic tension-type headache. Eur J Neurol 8:173–178PubMedCrossRef

50.

Sarchielli P, Alberti A, Codini M, Floridi A, Gallai V (2000) Nitric oxide, prostaglandin and trigeminal vasoactive peptides in internal jugular vein blood during spontaneous migraine attacks. Cephalalgia 20:903–918CrossRef

51.

Friberg L, Olesen J, Olsen TS, Karle A, Ekman R, Fahrenkrug J (1994) Absence of vasoactive peptide release from brain to cerebral circulation during onset of migraine with aura. Cephalalgia 14:47–54PubMedCrossRef

52.

Frese A, Schilgen M, Edvinsson L, Frandsen E, Evers S (2005) Calcitonin gene-related peptide in cervicogenic headache. Cephalalgia 25:700–703PubMedCrossRef

53.

Spanner R ed (1970) Spalteholz-Spanner Handatlas der Anatomie des Menchen, 16th edn. Second Part. Scheltema, Holkema, Amsterdam

54.

Shenkin HA, Harmel MN, Kety SS (1948) Dynamic anatomy of the cerebral circulation. Arch Neurol Psychiatry 60:240–252PubMedCrossRef

55.

Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B et al (2001) Mechanism of migraine aura revealed by functional MRI in the visual cortex. Proc Natl Acad Sci USA 98:4687–4692PubMedCentralPubMedCrossRef

56.

Olesen J, Friberg L, Olsen TS, Iversen HK, Lassen NA, Andersen AR, Karle A (1990) Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol 28:791–798PubMedCrossRef

57.

Iversen HK, Nielsen TH, Olesen J, Tfelt-Hansen P (1990) Arterial responses during migraine headaches. Lancet 336:837–839PubMedCrossRef

58.

Nielsen TH, Tfelt-Hansen P, Iversen HK (2009) Asymmetry of temporal arterial diameter during spontaneous attacks of cluster headache. Headache 49:383–385PubMedCrossRef

59.

Drummond PD, Gonski A, Lance JW (1983) Facial flushing after thermocoagulation of the Gasserian ganglion. J Neurol Neurosurg Psychiatr 46:611–616PubMedCentralPubMedCrossRef

60.

Drummond PD, Lance JW (1984) Thermographic changes in cluster headache. Neurology 34:1292–1298PubMedCrossRef

61.

Drummond PD, Lance JW (1984) Facial temperature in migraine, tension-vascular and tension headache. Cephalalgia 4:149–158PubMedCrossRef

62.

Petersen KA, Lassen LH, Birk S, Lesko L, Olesen J (2005) BIBN4096BS antagonizes human α-calcitonin gene related peptide-induced headache and extracerebral artery dilatation. Clin Pharmacol Ther 77:202–213PubMedCrossRef

Title: Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? A review
Authors: Peer Tfelt-Hansen
Han Le
Publication date: 01-06-2009
Publisher: Springer Milan
Published in: The Journal of Headache and Pain / Issue 3/2009
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1007/s10194-009-0112-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? A review

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2009

Psychiatric disorders and headache familial recurrence: a study on 200 children and their parents

Associations between headache and stress, alcohol drinking, exercise, sleep, and comorbid health conditions in a Japanese population

Post-traumatic headache: facts and doubts

Sarah T. Pendlebury, Matthew F. Giles, Peter M. Rothwell: Transient Ischemic Attack and Stroke: Diagnosis, Investigation and Management

Study on management of pediatric migraine by general practitioners in northern France

Coexistence of cluster headache and paroxysmal hemicrania: does it exist? A case report and literature review