| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Brain, Vol. 126, No. 1, 241-247,
January 2003
© 2003 Guarantors of Brain
doi: 10.1093/brain/awg009
Migraine can be induced by sildenafil without changes in middle cerebral artery diameter
Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, Copenhagen, Denmark
Correspondence to: C. Kruuse, MD, Department of Neurology, Glostrup Hospital, University of Copenhagen, DK-2600 Glostrup, Denmark E-mail: ckruuse{at}dadlnet.dk
Migraine is considered a neurovascular disease involving dilatation of cerebral arteries. Nitric oxide (NO) donors induce dilatation of cerebral and extracranial arteries and migraine, but NO has several mechanisms of action in addition to its cyclic guanosine monophosphate (cGMP)-mediated vasodilatation. We examined whether sildenafil (Viagra®), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. We included 12 patients with migraine without aura in this double-blind, placebo-controlled crossover study, in which placebo or sildenafil 100 mg was administered orally on two separate days. Blood flow velocity in the middle cerebral artery (Vmca) was recorded by transcranial Doppler ultrasonography and regional cerebral blood flow in the territory of the middle cerebral artery (rCBFmca) was measured using SPECT (single photon emission computed tomography) and xenon 133 inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasonography. Headache response, tenderness of pericranial muscles, blood pressure and heart rate were measured repeatedly. We found that migraine attack was induced by sildenafil in 10 of 12 migraine patients and by placebo in two of 12 patients (P = 0.01). Vmca (P = 0.1) and rCBFmca (P = 0.93) remained unchanged after sildenafil. Temporal (P = 0.47) and radial (P = 0.87) artery diameter and pericranial tenderness (P = 0.16) were unaffected by sildenafil. Systolic and diastolic blood pressures were unchanged but heart rate increased from a mean of 62 ± 2 to 74 ± 3 beats/min (P = 0.01) after sildenafil. Our results demonstrate that migraine may be induced via a cGMP-dependent mechanism, and we show for the first time that this occurs without initial dilatation of the middle cerebral artery. We propose that triggering mechanisms may reside within the perivascular sensory nerve terminals or the brainstem. However, other sites of action may also be possible and future studies are needed to elucidate this. In the clinical use of sildenafil, patients who have migraine should be informed about the risk of migraine attacks.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Schytz, T Wienecke, J Olesen, and M Ashina Carbachol induces headache, but not migraine-like attacks, in patients with migraine without aura Cephalalgia, March 1, 2010; 30(3): 337 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Wienecke, J Olesen, and M Ashina Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs Cephalalgia, February 1, 2010; 30(2): 179 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Charles and K. Brennan Cortical Spreading Depression--New Insights and Persistent Questions Cephalalgia, October 1, 2009; 29(10): 1115 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Schoonman and M. D. Ferrari Reply to: Migraine headache is not associated with cerebral or meningeal vasodilatation--a 3T magnetic resonance angiography study Brain, June 1, 2009; 132(6): e113 - e113. [Full Text] [PDF]
|
|
|
|
|
|
T Wienecke, J Olesen, P. Oturai, and M Ashina Prostaglandin E2 (PGE2) Induces Headache in Healthy Subjects Cephalalgia, May 1, 2009; 29(5): 509 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. T. Demchenko, A. Ruehle, B. W. Allen, R. D. Vann, and C. A. Piantadosi Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen J Appl Physiol, April 1, 2009; 106(4): 1234 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Lindholt, K. Petersen, J. Tvedskov, H. Iversen, J Olesen, and P Tfelt-Hansen Lack of Effect of Norepinephrine on Cranial Haemodynamics and Headache in Healthy Volunteers Cephalalgia, March 1, 2009; 29(3): 384 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Schytz, T Wieneckey, P. Oturai, J Olesen, and M Ashina The Cholinomimetic Agent Carbachol Induces Headache in Healthy Subjects Cephalalgia, February 1, 2009; 29(2): 258 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Schytz, S. Birk, T. Wienecke, C. Kruuse, J. Olesen, and M. Ashina PACAP38 induces migraine-like attacks in patients with migraine without aura Brain, January 1, 2009; 132(1): 16 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Schoonman, J. van der Grond, C. Kortmann, R. J. van der Geest, G. M. Terwindt, and M. D. Ferrari Migraine headache is not associated with cerebral or meningeal vasodilatation--a 3T magnetic resonance angiography study Brain, August 1, 2008; 131(8): 2192 - 2200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hansen, L. Thomsen, J Olesen, and M Ashina Familial Hemiplegic Migraine Type 1 Shows no Hypersensitivity to Nitric Oxide Cephalalgia, May 1, 2008; 28(5): 496 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Rahmann, T Wienecke, J. Hansen, J Fahrenkrug, J Olesen, and M Ashina Vasoactive Intestinal Peptide Causes Marked Cephalic Vasodilation, but does not Induce Migraine Cephalalgia, March 1, 2008; 28(3): 226 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Magis, L Bendtsen, P. Goadsby, A May, M S. d. Rio, P. Sandor, H Kaube, G Sandrini, G. Schoonman, J Schoenen, et al. Evaluation and Proposal for Optimization of Neurophysiological Tests In Migraine: Part 2--Neuroimaging and The Nitroglycerin Test Cephalalgia, December 1, 2007; 27(12): 1339 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Peterlin, M. Bigal, S. Tepper, M Urakaze, F. Sheftell, and A. Rapoport Migraine and Adiponectin: Is There a Connection? Cephalalgia, May 1, 2007; 27(5): 435 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hansen, D. Pedersen, V. Larsen, M Sanchez-del-Rio, J. A. Linera, J Olesen, and M Ashina Magnetic Resonance Angiography Shows Dilatation of the Middle Cerebral Artery after Infusion of Glyceryl Trinitrate in Healthy Volunteers Cephalalgia, February 1, 2007; 27(2): 118 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Birk, C Kruuse, K. Petersen, P Tfelt-Hansen, and J Olesen The Headache-Inducing Effect of Cilostazol in Human Volunteers Cephalalgia, November 1, 2006; 26(11): 1304 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Dinn and M. Wall Tadalafil Associated with Typical Migraine Aura without Headache Cephalalgia, November 1, 2006; 26(11): 1344 - 1346. [Full Text] [PDF]
|
|
|
|
|
|
C Kruuse, L. Lassen, H. Iversen, S Oestergaard, and J Olesen Dipyridamole May Induce Migraine in Patients With Migraine Without Aura Cephalalgia, August 1, 2006; 26(8): 925 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hansen, J Sitarz, S Birk, A. Rahmann, P. Oturai, J Fahrenkrug, J Olesen, and M Ashina Vasoactive Intestinal Polypeptide Evokes Only a Minimal Headache in Healthy Volunteers Cephalalgia, August 1, 2006; 26(8): 992 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M de L Figuerola, O Bruera, J Leston, and J Ferreiro Cluster Headache Attack due to Sildenafil Intake Cephalalgia, May 1, 2006; 26(5): 617 - 619. [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Goadsby Advances in the understanding of headache Br. Med. Bull., October 5, 2005; 73-74(1): 83 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Diomedi, F. Sallustio, B. Rizzato, F. Ferrante, G. Leone, E. Spera, M. Scarfini, and G. Bernardi Sildenafil increases cerebrovascular reactivity: A transcranial Doppler study Neurology, September 27, 2005; 65(6): 919 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Birk, K. Petersen, C Kruuse, R Guieu, O Jonassen, W Eisert, and J Olesen The Effect of Circulating Adenosine on Cerebral Haemodynamics and Headache Generation in Healthy Subjects Cephalalgia, May 1, 2005; 25(5): 369 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Ghofrani, F. Reichenberger, M. G. Kohstall, E. H. Mrosek, T. Seeger, H. Olschewski, W. Seeger, and F. Grimminger Sildenafil Increased Exercise Capacity during Hypoxia at Low Altitudes and at Mount Everest Base Camp: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial Ann Intern Med, August 3, 2004; 141(3): 169 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Levy and A. M. Strassman Modulation of Dural Nociceptor Mechanosensitivity by the Nitric Oxide-Cyclic GMP Signaling Cascade J Neurophysiol, August 1, 2004; 92(2): 766 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Kruuse, E Frandsen, S Schifter, L. Thomsen, S Birk, and J Olesen Plasma Levels of cAMP, cGMP and CGRP in Sildenafil-Induced Headache Cephalalgia, July 1, 2004; 24(7): 547 - 553. [Abstract] [Full Text] [PDF]
|
|