Carbachol induces headache, but not migraine-like attacks, in patients with migraine without aura
HW Schytz
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
Search for more papers by this authorT Wienecke
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
Search for more papers by this authorJ Olesen
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
Search for more papers by this authorM Ashina
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
Search for more papers by this authorHW Schytz
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
Search for more papers by this authorT Wienecke
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
Search for more papers by this authorJ Olesen
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
Search for more papers by this authorM Ashina
Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Glostrup, Denmark
Search for more papers by this authorAbstract
Carbachol induces headache in healthy subjects, but the migraine eliciting effect of carbachol has not previously been studied. We hypothesized that the cholinomimetic agonist carbachol would induce headache and migraine-like attacks in migraineurs. Carbachol (3 µg/kg) or placebo was randomly infused into 18 patients with migraine without aura in a double-blind crossover study. Headache was scored on a verbal rating scale from 0 to 10. Velocity in the middle cerebral artery (VMCA) and diameter of the superficial temporal artery (STA) were recorded. Fifteen patients experienced headache after carbachol compared with eight after placebo (P = 0.039). There was no difference in incidence of migraine-like attacks after carbachol (n = 8) compared with placebo (n = 6) (P = 0.687). Carbachol caused a decrease in VMCA (P = 0.044), but no change in STA (P = 0.089) compared with placebo. The study demonstrated that carbachol provocation is not a good model for experimental migraine.
References
- 1 Edvinsson L, Uddman R. Adrenergic, cholinergic and peptidergic nerve fibres in dura mater—involvement in headache? Cephalalgia 1981; 1: 175–9.
- 2 Edvinsson L, Gulbenkian S, Barroso CP, Cunha e Sa M, Polak JM, Mortensen A et al. Innervation of the human middle meningeal artery: immunohistochemistry, ultrastructure, and role of endothelium for vasomotility. Peptides 1998; 19: 1213–25.
- 3 Yu JG, Kimura T, Chang XF, Lee TJ. Segregation of VIPergic-nitric oxidergic and cholinergic-nitric oxidergic innervation in porcine middle cerebral arteries. Brain Res 1998; 801: 78–87.
- 4 Faraci FM. Role of nitric oxide in regulation of basilar artery tone in vivo. Am J Physiol 1990; 259: H1216–21.
- 5 Faraci FM. Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation. Am J Physiol 1991; 261: H1038–42.
- 6 Elhusseiny A, Hamel E. Muscarinic—but not nicotinic—acetylcholine receptors mediate a nitric oxide-dependent dilation in brain cortical arterioles: a possible role for the M5 receptor subtype. J Cereb Blood Flow Metab 2000; 20: 298–305.
- 7 Kowacs F, Williamson DJ, Goadsby PJ. Neurogenic vasodilation of dural blood vessels is not mediated by cholinergic transmission in the anaesthetised rat. Eur J Pharmacol 2004; 493: 133–7.
- 8 Imaizumi T, Hirooka Y, Masaki H, Harada S, Momohara M, Tagawa T, Takeshita A. Effects of L-arginine on forearm vessels and responses to acetylcholine. Hypertension 1992; 20: 511–17.
- 9 Jansen I, Uddman R, Ekman R, Olesen J, Ottosson A, Edvinsson L. Distribution and effects of neuropeptide Y, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide in human middle meningeal arteries: comparison with cerebral and temporal arteries. Peptides 1992; 13: 527–36.
- 10 Rozniecki JJ, Dimitriadou V, Lambracht-Hall M, Pang X, Theoharides TC. Morphological and functional demonstration of rat dura mater mast cell-neuron interactions in vitro and in vivo. Brain Res 1999; 849: 1–15.
- 11 Delepine L, Aubineau P. Plasma protein extravasation induced in the rat dura mater by stimulation of the parasympathetic sphenopalatine ganglion. Exp Neurol 1997; 147: 389–400.
- 12 Tanelian DL. Cholinergic activation of a population of corneal afferent nerves. Exp Brain Res 1991; 86: 414–20.
- 13 Steen KH, Reeh PW. Actions of cholinergic agonists and antagonists on sensory nerve endings in rat skin, in vitro. J Neurophysiol 1993; 70: 397–405.
- 14 Armstrong D, Dry RM, Keele CA, Markham JW. Observations on chemical excitants of cutaneous pain in man. J Physiol 1953; 120: 326–51.
- 15 Wilson ASH. The effect of the injection of acetylcholine into the brachial artery of normal subjects and patients with myasthenia gravis. Q J Med 1947; 16: 237–43.
- 16 Schytz HW, Wienecke T, Oturai PS, Olesen J, Ashina M. The cholinomimetic agent carbachol induces headache in healthy subjects. Cephalalgia 2009; 29: 258–68.
- 17 Hamilton CA, Williams R, Pathi V, Berg G, McArthur K, McPhaden AR et al. Pharmacological characterization of endothelium-dependent relaxation in human radial artery: comparison with internal thoracic artery. Cardiovasc Res 1999; 42: 214–23.
- 18 Hardman JG, Limbird LE, Gilman AG. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 10th edn. New York: McGraw-Hill 2001.
- 19 IHS. The International Classification of Headache Disorders, 2nd edn. Cephalalgia 2004; 24 (Suppl. 1): 9–160.
- 20 Iversen HK, Olesen J, Tfelt-Hansen P. Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics. Pain 1989; 38: 17–24.
- 21
Iversen LLKC,
Thomsen HK,
Olesen J.
A nitric oxide donor triggers genuine migraine attacks.
Eur J Neurol
1994; 1: 73–80.
10.1111/j.1468-1331.1994.tb00053.x Google Scholar
- 22 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.
- 23 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.
- 24 Iversen LLAM, Thomsen HK, Olesen J., eds. Middle cerebral artery blood flow velocity increases during experimental pressure pain in the head. Philadelphia, PA: Lippincott-Raven Publishers, 1995.
- 25 Thomsen LL, Iversen HK. Experimental and biological variation of three-dimensional transcranial Doppler measurements. J Appl Physiol 1993; 75: 2805–10.
- 26 Dahl A, Russell D, Nyberg-Hansen R, Rootwelt K. Effect of nitroglycerin on cerebral circulation measured by transcranial Doppler and SPECT. Stroke 1989; 20: 1733–6.
- 27 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.
- 28 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.
- 29 Iversen HK, Nielsen TH, Olesen J, Tfelt-Hansen P. Arterial responses during migraine headache. Lancet 1990; 336: 837–9.
- 30 Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ 1990; 300: 230–5.
- 31 Tvedskov JF, Thomsen LL, Iversen HK, Williams P, Gibson A, Jenkins K et al. The effect of propranolol on glyceryltrinitrate-induced headache and arterial response. Cephalalgia 2004; 24: 1076–87.
- 32 McCulloch AI, Bottrill FE, Randall MD, Hiley CR. Characterization and modulation of EDHF-mediated relaxations in the rat isolated superior mesenteric arterial bed. Br J Pharmacol 1997; 120: 1431–8.
- 33 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.
- 34 Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M. PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain 2008.
- 35 Dong H, Waldron GJ, Cole WC, Triggle CR. Roles of calcium-activated and voltage-gated delayed rectifier potassium channels in endothelium-dependent vasorelaxation of the rabbit middle cerebral artery. Br J Pharmacol 1998; 123: 821–32.
- 36 Wienecke T, Olesen J, Oturai PS, Ashina M. Prostacyclin (epoprostenol) induces headache in healthy subjects. Pain 2008; 139: 106–16.
