Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs
T Wienecke
Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Copenhagen, Denmark
Search for more papers by this authorJ Olesen
Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Copenhagen, Denmark
Search for more papers by this authorM Ashina
Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Copenhagen, Denmark
Search for more papers by this authorT Wienecke
Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Copenhagen, Denmark
Search for more papers by this authorJ Olesen
Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Copenhagen, Denmark
Search for more papers by this authorM Ashina
Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Copenhagen, Denmark
Search for more papers by this authorAbstract
Prostacyclin [prostaglandin I2 (PGI2)] activates and sensitizes meningeal sensory afferents. In healthy subjects PGI2 triggers headache in healthy subjects. However, the migraine-eliciting effect of PGI2 has not been systematically studied in patients with migraine. We hypothesized that intravenous infusion of the stable prostacyclin analogue epoprostenol would trigger migraine-like attacks in migraineurs. We infused 10 ng kg−1 min−1 PGI2 or placebo over 25 min in 12 migraineurs without aura in a controlled, double-blind, cross-over study and recorded headache intensity and associated symptons, velocity in the middle cerebral artery (VMCA) and diameter in the superficial temporal artery. In the period 0–14 h, 12 subjects reported headache on PGI2 day compared with three subjects on placebo day (P = 0.004), and six subjects fulfilled the criteria for an experimentally induced migraine-like attack compared with two subjects on placebo (P = 0.219). During infusion and post-infusion phases the AUC under the headache curve on PGI2 was significantly larger than on placebo (P < 0.05). There was a significant VMCA decrease (P = 0.015) and superficial temporal artery diameter increase (P < 0.001) on PGI2 compared with placebo. In conclusion, PGI2 may trigger a migraine-like attack in migraine sufferers. We suggest sensitization of perivascular nociceptors and arterial dilation as the mode of action of PGI2-induced headache and migraine-like attacks.
References
- 1 Thomsen LL, Olesen J. Nitric oxide in primary headaches. Curr Opin Neurol 2001; 14: 315–21.
- 2 Thomsen LL, Kruuse C, Iversen HK, Olesen J. A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks. Eur J Neurol 1994; 1: 73–80.
- 3 Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia 2002; 22: 54–61.
- 4 Lassen LH, Ashina M, Christiansen I, Ulrich V, Olesen J. Nitric oxide synthase inhibition in migraine. Lancet 1997; 349: 401–2.
- 5 Petersen KA, Lassen LH, Birk S, Lesko L, Olesen J. BIBN4096BS antagonizes human alpha-calcitonin gene related peptide-induced headache and extracerebral artery dilatation. Clin Pharmacol Ther 2005; 77: 202–13.
- 6 Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U et al. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 2004; 350: 1104–10.
- 7 Tfelt-Hansen P. Nonsteroidal anti-inflammatory drugs in the acute treatment of migraines. In: JGP Olesen, NM Ramadan, P Tfelt-Hansen, KMA Welch, eds. The headaches, 3rd edn. Philadelphia, PA: Lippincott Williams & Wilkins 2006: 449–57.
- 8 Diener HC. Efficacy and safety of intravenous acetylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine. A double-blind, double-dummy, randomized, multicenter, parallel group study. The ASASUMAMIG Study Group. Cephalalgia 1999; 19: 581–8. discussion 42.
- 9 Ito S, Okuda-Ashitaka E, Minami T. Central and peripheral roles of prostaglandins in pain and their interactions with novel neuropeptides nociceptin and nocistatin. Neurosci Res 2001; 41: 299–332.
- 10 Hata AN, Breyer RM. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther 2004; 103: 147–66.
- 11 Roberts LJ 2nd, Lewis RA, Oates JA, Austen KF. Prostaglandin thromboxane, and 12-hydroxy-5,8,10,14-eicosatetraenoic acid production by ionophore-stimulated rat serosal mast cells. Biochim Biophys Acta 1979; 575: 185–92.
- 12 Zonta M, Sebelin A, Gobbo S, Fellin T, Pozzan T, Carmignoto G. Glutamate-mediated cytosolic calcium oscillations regulate a pulsatile prostaglandin release from cultured rat astrocytes. J Physiol 2003; 553: 407–14.
- 13 Hull M, Muksch B, Akundi RS, Waschbisch A, Hoozemans JJ, Veerhuis R et al. Amyloid beta peptide (25-35) activates protein kinase C leading to cyclooxygenase-2 induction and prostaglandin E2 release in primary midbrain astrocytes. Neurochem Int 2006; 48: 663–72.
- 14 Liao SL, Ou YC, Chen SY, Chiang AN, Chen CJ. Induction of cyclooxygenase-2 expression by manganese in cultured astrocytes. Neurochem Int 2007; 50: 905–15.
- 15 Hirst WD, Young KA, Newton R, Allport VC, Marriott DR, Wilkin GP. Expression of COX-2 by normal and reactive astrocytes in the adult rat central nervous system. Mol Cell Neurosci 1999; 13: 57–68.
- 16 Zhang XC, Strassman AM, Burstein R, Levy D. Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther 2007; 322: 806–12.
- 17 Strassman AM, Raymond SA, Burstein R. Sensitization of meningeal sensory neurons and the origin of headaches. Nature 1996; 384: 560–4.
- 18 Wienecke T, Olesen J, Oturai PS, Ashina M. Prostacyclin (epoprostenol) induces headache in healthy subjects. Pain 2008; 139: 106–16.
- 19 Olesen J, Iversen HK, Thomsen LL. Nitric oxide supersensitivity: a possible molecular mechanism of migraine pain. Neuroreport 1993; 4: 1027–30.
- 20 Vane J, Corin RE. Prostacyclin: a vascular mediator. Eur J Vasc Endovasc Surg 2003; 26: 571–8.
- 21 IHS. The International Classification of Headache Disorders, 2nd edn. Cephalalgia 2004; 24 (Suppl. 1): 9–160.
- 22 Giffin NJ, Ruggiero L, Lipton RB, Silberstein SD, Tvedskov JF, Olesen J et al. Premonitory symptoms in migraine: an electronic diary study. Neurology 2003; 60: 935–40.
- 23 Jakubowski M, Silberstein S, Ashkenazi A, Burstein R. Can allodynic migraine patients be identified interictally using a questionnaire? Neurology 2005; 65: 1419–22.
- 24 Iversen HK, Olesen J, Tfelt-Hansen P. Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics. Pain 1989; 38: 17–24.
- 25 Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ et al. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 2006; 26: 742–6.
- 26 Thomsen LL, Iversen HK. Experimental and biological variation of three-dimensional transcranial Doppler measurements. J Appl Physiol 1993; 75: 2805–10.
- 27 Hansen JM, Sitarz J, Birk S, Rahmann AM, Oturai PS, Fahrenkrug J et al. Vasoactive intestinal polypeptide evokes only a minimal headache in healthy volunteers. Cephalalgia 2006; 26: 992–1003.
- 28 Markwalder TM, Grolimund P, Seiler RW, Roth F, Aaslid R. Dependency of blood flow velocity in the middle cerebral artery on end-tidal carbon dioxide partial pressure—a transcranial ultrasound Doppler study. J Cereb Blood Flow Metab 1984; 4: 368–72.
- 29 Nielsen TH, Iversen HK, Tfelt-Hansen P, Olesen J. Small arteries can be accurately studied in vivo, using high frequency ultrasound. Ultrasound Med Biol 1993; 19: 717–25.
- 30 Iversen HK, Nielsen TH, Olesen J, Tfelt-Hansen P. Arterial responses during migraine headache. Lancet 1990; 336: 837–9.
- 31 Longenecker LL, McNeil A, Longenecker GL. Plasma protein binding and biologic half-life of prostacyclin in steady state sickle cell disease. Thromb Res 1991; 64: 751–6.
- 32 De Leval X, Hanson J, David JL, Masereel B, Pirotte B, Dogne JM. New developments on thromboxane and prostacyclin modulators part II: prostacyclin modulators. Curr Med Chem 2004; 11: 1243–52.
- 33 Hassan S, Pickles H. Epoprostenol (prostacyclin, PGI2) increases apparent liver blood flow in man. Prostaglandins Leukot Med 1983; 10: 449–54.
- 34 Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ 1990; 300: 230–5.
- 35 Peatfield RC, Gawel MJ, Rose FC. The effect of infused prostacyclin in migraine and cluster headache. Headache 1981; 21: 190–5.
- 36
Ray BS,
Wolff HG.
Experimental studies on headache: pain sensitive structures of the head and their significance in headache.
Arch Surg
1940; 1: 813–56.
10.1001/archsurg.1940.01210040002001 Google Scholar
- 37 Nichols FT 3rd, Mawad M, Mohr JP, Stein B, Hilal S, Michelsen WJ. Focal headache during balloon inflation in the internal carotid and middle cerebral arteries. Stroke 1990; 21: 555–9.
- 38 Friberg L, Olesen J, Iversen HK, Sperling B. Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan. Lancet 1991; 338: 13–17.
- 39 Kruuse C, Thomsen LL, Birk S, Olesen J. Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain 2003; 126: 241–7.
- 40 Schoonman GG, Van Der Grond J, Kortmann C, Van Der Geest RJ, Terwindt GM, Ferrari MD. Migraine headache is not associated with cerebral or meningeal vasodilatation—a 3T magnetic resonance angiography study. Brain 2008; 1.
- 41 Lassen LH, Jacobsen VB, Haderslev PA, Sperling B, Iversen HK, Olesen J et al. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients. J Headache Pain 2008; 9: 151–7.
- 42 Levy D, Burstein R, Strassman AM. Calcitonin gene-related peptide does not excite or sensitize meningeal nociceptors: implications for the pathophysiology of migraine. Ann Neurol 2005; 58: 698–705.
- 43 Rahmann A, Wienecke T, Hansen JM, Fahrenkrug J, Olesen J, Ashina M. Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia 2008; 28: 226–36.
- 44 Lassen LH, Heinig JH, Oestergaard S, Olesen J. Histamine inhalation is a specific but insensitive laboratory test for migraine. Cephalalgia 1996; 16: 550–3.
- 45 Boie Y, Rushmore TH, Darmon-Goodwin A, Grygorczyk R, Slipetz DM, Metters KM et al. Cloning and expression of a cDNA for the human prostanoid IP receptor. J Biol Chem 1994; 269: 12173–8.
- 46 Katsuyama M, Sugimoto Y, Namba T, Irie A, Negishi M, Narumiya S et al. Cloning and expression of a cDNA for the human prostacyclin receptor. FEBS Lett 1994; 344: 74–8.
- 47 Nakagawa O, Tanaka I, Usui T, Harada M, Sasaki Y, Itoh H et al. Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system. Circulation 1994; 90: 1643–7.
- 48 Birk S, Kruuse C, Petersen KA, Tfelt-Hansen P, Olesen J. The headache-inducing effect of cilostazol in human volunteers. Cephalalgia 2006; 26: 1304–9.
- 49 Levy D, Strassman AM. Distinct sensitizing effects of the cAMP-PKA second messenger cascade on rat dural mechanonociceptors. J Physiol 2002; 538: 483–93.
- 50 Goadsby PJMA, Edvinsson L. Primary neurovascular headache. Migraine and cluster headache from a physiologic perspective. In: DN ElaK, ed. Cerebral blood floow and metabolism, 2nd edn. Philadelphia, PA: Lippincott Williams & Wilkins 2002: 457–65.
- 51 Jenkins DW, Feniuk W, Humphrey PP. Characterization of the prostanoid receptor types involved in mediating calcitonin gene-related peptide release from cultured rat trigeminal neurones. Br J Pharmacol 2001; 134: 1296–302.
- 52 Davis RJ, Murdoch CE, Ali M, Purbrick S, Ravid R, Baxter GS et al. EP4 prostanoid receptor-mediated vasodilatation of human middle cerebral arteries. Br J Pharmacol 2004; 141: 580–5.
- 53 Levy D, Zhang XC, Jakubowski M, Burstein R. Sensitization of meningeal nociceptors: inhibition by naproxen. Eur J Neurosci 2008; 27: 917–22.
- 54 Jakubowski M, Levy D, Goor-Aryeh I, Collins B, Bajwa Z, Burstein R. Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors. Headache 2005; 45: 850–61.
- 55 Coleman RA, Smith WL, Narumiya S. International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 1994; 46: 205–29.
- 56 Wise H, Jones RL. Focus on prostacyclin and its novel mimetics. Trends Pharmacol Sci 1996; 17: 17–21.
- 57 Siegel G, Carl A, Adler A, Stock G. Effect of the prostacyclin analogue iloprost on K+ permeability in the smooth muscle cells of the canine carotid artery. Eicosanoids 1989; 2: 213–22.
- 58 Schubert R, Serebryakov VN, Mewes H, Hopp HH. Iloprost dilates rat small arteries: role of K(ATP)- and K(Ca)-channel activation by cAMP-dependent protein kinase. Am J Physiol 1997; 272: H1147–56.
- 59 Burstein R. Deconstructing migraine headache into peripheral and central sensitization. Pain 2001; 89: 107–10.
- 60 Burstein R, Collins B, Jakubowski M. Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol 2004; 55: 19–26.
- 61 Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH. An association between migraine and cutaneous allodynia. Ann Neurol 2000; 47: 614–24.
- 62 Burstein R, Cutrer MF, Yarnitsky D. The development of cutaneous allodynia during a migraine attack clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain 2000; 123: 1703–9.
- 63 Nakae K, Hayashi F, Hayashi M, Yamamoto N, Iino T, Yoshikawa S et al. Functional role of prostacyclin receptor in rat dorsal root ganglion neurons. Neurosci Lett 2005; 388: 132–7.
- 64 Afridi SK, Kaube H, Goadsby PJ. Glyceryl trinitrate triggers premonitory symptoms in migraineurs. Pain 2004; 110: 675–80.
- 65 Sances G, Tassorelli C, Pucci E, Ghiotto N, Sandrini G, Nappi G. Reliability of the nitroglycerin provocative test in the diagnosis of neurovascular headaches. Cephalalgia 2004; 24: 110–19.
- 66 Christiansen I, Thomsen LL, Daugaard D, Ulrich V, Olesen J. Glyceryl trinitrate induces attacks of migraine without aura in sufferers of migraine with aura. Cephalalgia 1999; 19: 660–7. discussion 26.
- 67 Lassen LH, Thomsen LL, Olesen J. Histamine induces migraine via the H1-receptor. Support for the NO hypothesis of migraine. Neuroreport 1995; 6: 1475–9.