Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38

被引:199
作者
Amin, Faisal Mohammad [1 ,2 ]
Hougaard, Anders [1 ,2 ]
Schytz, Henrik W. [1 ,2 ]
Asghar, Mohammad S. [1 ,2 ]
Lundholm, Elisabet [1 ,2 ]
Parvaiz, Arushma I. [1 ,2 ]
de Koning, Patrick J. H. [3 ]
Andersen, Malene R. [4 ]
Larsson, Henrik B. W. [5 ]
Fahrenkrug, Jan [6 ]
Olesen, Jes [1 ,2 ]
Ashina, Messoud [1 ,2 ]
机构
[1] Univ Copenhagen, Fac Hlth & Med Sci, Glostrup Hosp, Danish Headache Ctr, DK-2600 Glostrup, Denmark
[2] Univ Copenhagen, Fac Hlth & Med Sci, Glostrup Hosp, Dept Neurol, DK-2600 Glostrup, Denmark
[3] Leiden Univ, Med Ctr, Dept Radiol, Div Image Proc, NL-2300 RA Leiden, Netherlands
[4] Univ Copenhagen, Gentofte Hosp, Dept Clin Biochem, DK-2600 Glostrup, Denmark
[5] Univ Copenhagen, Fac Hlth & Med Sci, Glostrup Hosp, Funct Imaging Unit,Diagnost Dept, DK-2600 Glostrup, Denmark
[6] Univ Copenhagen, Fac Hlth & Med Sci, Bispebjerg Hosp, Dept Clin Biochem, DK-2600 Glostrup, Denmark
关键词
imaging; migraine pathogenesis; human pain models; VASOACTIVE-INTESTINAL-PEPTIDE; MAST-CELL DEGRANULATION; PACAP RECEPTORS; MESSENGER-RNA; PHARMACOLOGICAL CHARACTERIZATION; CEREBRAL HEMODYNAMICS; BLOOD-VESSELS; HEADACHE; VIP; EXPRESSION;
D O I
10.1093/brain/awt369
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide are structurally and functionally closely related but show differences in migraine-inducing properties. Mechanisms responsible for the difference in migraine induction are unknown. Here, for the first time, we present a head-to-head comparison study of the immediate and long-lasting observations of the migraine-inducing, arterial, physiological and biochemical responses comparing PACAP38 and vasoactive intestinal polypeptide. In a double-blind crossover study 24 female migraine patients without aura were randomly allocated to intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We recorded incidence of migraine during and after infusion (0-24 h). Magnetic resonance angiography of selected extra-and intracranial arteries, blood samples (plasma PACAP38 and vasoactive intestinal polypeptide and serum tryptase), and vital signs (blood pressure, heart rate, respiratory frequency, and end-tidal pressure of CO2) was recorded before and up to 5 h after infusion. Twenty-two patients [mean age 24 years (range 19-36)] completed the study on both days. Sixteen patients (73%) reported migraine-like attacks after PACAP38 and four after vasoactive intestinal polypeptide (18%) infusion (P = 0.002). Three of four patients, who reported migraine-like attacks after vasoactive intestinal polypeptide, also reported attacks after PACAP38. Both peptides induced marked dilatation of the extracranial (P < 0.05), but not intracranial arteries (P > 0.05). PACAP38-induced vasodilatation was longer lasting (>2 h), whereas vasoactive intestinal polypeptide-induced dilatation was normalized after 2 h. We recorded elevated plasma PACAP38 at 1 h after the start of PACAP38 infusion only in those patients who later reported migraine attacks. Blood levels of vasoactive intestinal polypeptide and tryptase were unchanged after PACAP38 infusion. In conclusion, PACAP38-induced migraine was associated with sustained dilatation of extracranial arteries and elevated plasma PACAP38 before onset of migraine-like attacks. PACAP38 has a much higher affinity for the PAC(1) receptor and we therefore suggest that migraine induction by PACAP38 may be because of activation of the PAC(1) receptor, which may be a future anti-migraine drug target.
引用
收藏
页码:779 / 794
页数:16
相关论文
共 51 条
[1]  
Altman DG., 1996, PRACTICAL STAT MED R, V7th
[2]   The effect of sumatriptan on cephalic arteries: A 3T MR-angiography study in healthy volunteers [J].
Amin, Faisal Mohammad ;
Asghar, Mohammad Sohail ;
Ravneberg, Julie W. ;
de Koning, Patrick J. H. ;
Larsson, Henrik B. W. ;
Olesen, Jes ;
Ashina, Messoud .
CEPHALALGIA, 2013, 33 (12) :1009-1016
[3]   Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study [J].
Amin, Faisal Mohammad ;
Asghar, Mohammad Sohail ;
Hougaard, Anders ;
Hansen, Adam Espe ;
Larsen, Vibeke Andree ;
de Koning, Patrick J. H. ;
Larsson, Henrik B. W. ;
Olesen, Jes ;
Ashina, Messoud .
LANCET NEUROLOGY, 2013, 12 (05) :454-461
[4]   Headache and prolonged dilatation of the middle meningeal artery by PACAP38 in healthy volunteers [J].
Amin, Faisal Mohammad ;
Asghar, Mohammad Sohail ;
Guo, Song ;
Hougaard, Anders ;
Hansen, Adam Espe ;
Schytz, Henrik Winther ;
van der Geest, Rob J. ;
de Koning, Patrick J. H. ;
Larsson, Henrik B. W. ;
Olesen, Jes ;
Ashina, Messoud .
CEPHALALGIA, 2012, 32 (02) :140-149
[5]   Homeodomain Protein Otp and Activity-Dependent Splicing Modulate Neuronal Adaptation to Stress [J].
Amir-Zilberstein, Liat ;
Blechman, Janna ;
Sztainberg, Yehezkel ;
Norton, William N. J. ;
Reuveny, Adriana ;
Borodovsky, Nataliya ;
Tahor, Maayan ;
Bonkowsky, Joshua L. ;
Bally-Cuif, Laure ;
Chen, Alon ;
Levkowitz, Gil .
NEURON, 2012, 73 (02) :279-291
[6]   Evidence for a Vascular Factor in Migraine [J].
Asghar, Mohammad S. ;
Hansen, Adam E. ;
Amin, Faisal M. ;
van der Geest, R. J. ;
van der Koning, Patrick ;
Larsson, Henrik B. W. ;
Olesen, Jes ;
Ashina, Messoud .
ANNALS OF NEUROLOGY, 2011, 69 (04) :635-645
[7]   Dural mast cell degranulation is a putative mechanism for headache induced by PACAP-38 [J].
Baun, Michael ;
Pedersen, Martin Holst Friborg ;
Olesen, Jes ;
Jansen-Olesen, Inger .
CEPHALALGIA, 2012, 32 (04) :337-345
[8]   Pharmacological characterization and expression of VIP and PACAP receptors in isolated cranial arteries of the rat [J].
Baun, Michael ;
Hay-Schmidt, Anders ;
Edvinsson, Lars ;
Olesen, Jes ;
Jansen-Olesen, Inger .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2011, 670 (01) :186-194
[9]   The effect of circulating adenosine on cerebral haemodynamics and headache generation in healthy subjects [J].
Birk, S ;
Petersen, KA ;
Kruuse, C ;
Guieu, R ;
Jonassen, O ;
Eisert, W ;
Olesen, J .
CEPHALALGIA, 2005, 25 (05) :369-377
[10]   The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers [J].
Birk, Steffen ;
Sitarz, John Thomas ;
Petersen, Kenneth Ahrend ;
Oturai, Peter Sandor ;
Kruuse, Christina ;
Fahrenkrug, Jan ;
Olesen, Jes .
REGULATORY PEPTIDES, 2007, 140 (03) :185-191