Abstracts of the 2013 International Headache Congress

Volume 33, Number 8 (Supplement) June 2013

ISSN 0333-1024 (Print) ISSN 1468-2982 (Online)

Abstracts of the 2013 International Headache Congress International Headache Society and American Headache Society 27–30 June 2013 John B. Hynes Veterans Memorial Convention Center Boston, MA

www.ihs-headache.org http://cep.sagepub.com

IHC 2013 Program Abstracts Cephalalgia 33(8 Supplement) 1–291 ! International Headache Society 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102413490487 cep.sagepub.com

OR1 Optical and Selective Activation of Astrocytes Can Trigger Cortical Spreading Depression

ChR2 mice but not from controls. The OIS characteristics of optically triggered CSD were different from those associated with KCl-evoked CSD, suggesting distinct cellular responses.

S.M. Baca, R.T. Jones, C.J. Dietz, I. Mody, A. Charles Neurology, University of California, Los Angeles, Los Angeles, CA, USA. Objectives: We tested the hypotheses that direct optical activation of astrocytes is sufficient to initiate cortical spreading depression (CSD) and that CSD can be evoked by methods that do not involve deformation or damage of tissue, supra-physiological levels of potassium, or the application of exogenous drugs. Background: CSD is a slowly propagated wave of electrical and vascular activity that is believed to underlie the migraine aura, and CSD is also triggered by local injury to the brain. The cellular mechanisms by which CSD could be spontaneously triggered remain poorly understood. In experimental models, CSD is commonly elicited by pinprick to the cortical surface, by application of high concentrations of KCl, or by tetanic electrical stimulation. Here, we investigated a less invasive, cell-specific method of triggering CSD. Methods: The channelrhodopsin-2 (ChR2) receptor was selectively expressed in GFAPþ cells in mice. For in vitro investigations, hippocampal slices were prepared from these GFAP-ChR2 mice. For in vivo studies, mice were anesthetized, a thinned-skull cortical window was made, and a tungsten electrode and fiber optic were inserted through separate burr holes. For both preparations, a 473nm laser coupled to a fiber optic activated ChR2, and CSD was visualized with optical intrinsic signal imaging (OIS) and recorded as changes in local field potential. Results: In GFAP-ChR2 mice, activation of ChR2 with blue light elicited CSD, whereas the same intensity and duration of light exposure produced no CSD in wildtype littermate controls. Similarly, blue light activated spreading depression in hippocampal slices from GFAP-

Conclusions: These studies indicate that astrocytes can play a primary role in the initiation of CSD, and that CSD can be generated by a relatively non-invasive optical approach.

OR2 Magnetic Resonance Angiography Reveals Intracranial but No Extracranial Arterial Dilatation during Migraine Attacks F.M. Amin1, M.S. Asghar1, A. Hougaard1, A.E. Hansen2, V.A. Larsen3, P.J.H. de Koning4, H.B.W. Larsson2, J. Olesen1, M. Ashina1 1

Danish Headache Center, Department of Neurology, Glostrup Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark; 2Functional Imaging Unit, Diagnostic Department, Glostrup Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark; 3Department of Radiology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 4 Division of Image Processing, Leiden University Medical Center, Leiden, The Netherlands. Objectives: The aim of the present study was to measure extracranial and intracranial arteries during attacks of migraine without aura. Background: Extracranial arterial dilatation has clinically been considered the cause of pain in patients suffering from migraine without aura. Methods: We performed high-resolution magnetic resonance angiography (MRA) in 24 female patients with migraine without aura during spontaneous unilateral migraine attacks. Fifteen patients were also scanned

2 30 min after treatment with 6 mg subcutaneous sumatriptan. Primary endpoints were difference in circumference of extra- and intracranial arterial segments comparing the pain and the non-pain side and the attack and attack-free day. The extracranial arterial segments included: the external carotid (ECA), the superficial temporal (STA), the middle meningeal (MMA) and the cervical part of the internal carotid (ICAcervical) artery. The intracranial arterial segments were: the cavernous (ICAcavernous) and cerebral (ICAcerebral) parts of the internal carotid, the middle cerebral (MCA) and the basilar artery (BA). Results: We found no dilatation of the ECA, MMA, STA, ICAcervical or BA (p > 0.05). The ICAcavernous and ICAcerebral were dilated (10.5%, 10.2%) on the pain side compared to the non-pain side (p  0.02). The MCA was dilated on both sides during attack (p < 0.05). Administration of sumatriptan caused constriction of the extracranial arteries (p  0.034) but the ICAcerebral and the MCA remained unchanged (p  0.124). Conclusions: Migraine pain was not accompanied by extracranial arterial dilatation and only by slight intracranial dilatation. Sumatriptan relieved the headache and constricted extracerebral, but did not constrict the dilated cerebral arteries.

OR3 Light of Intrinsically Photosensitive Retinal Ganglion Cell (ipRGC) Causing Migraine Headache Exacerbation M. Tatsumoto1, T. Eda2, T. Ishikawa3, M. Ayama3, K. Hirata1 1

Neurology, Dokkyo Medical University, Shimotsuga, Tochigi, Japan; 2Education Center of Medical Informatics, International University of Health and Welfare, Ohtawara, Tochigi, Japan; 3Advanced Interdisciplinary Sciences, Graduate School of Engineering, Utsunomiya University, Utsunomiya, Tochigi, Japan. Objectives: The peak wavelength of intrinsically photosensitive retinal ganglion cells (ipRGC) differs from those of rod and cone cells. This study was conducted with the objective of determining whether light stimulation by the peak wavelength of ipRGC might induce migraines. Background: Recently, a study revealed that both the extrinsic photoactivation of ipRGC and the intrinsic photoactivation of melanopsin may be involved in the exacerbation of migraines by light stimulation. However, light-induced migraine attacks triggered by the peak wavelength (480nm) of ipRGC have not yet been reported.

Cephalalgia 33(8 Supplement) Methods: We investigated the threshold for uncomfortable glare created by light stimulation. The first study population consisted of 46 consecutive migraine patients. Headaches were diagnosed based on the ICHD-II criteria. Light stimulation was achieved using light-emitting diodes through the interference filter which permeabilized three different specific wavelengths (480nm, 550nm, 610nm). The subjects were allowed to adapt in a darkroom for 5 min. They were then asked to evaluate the discomfort glare caused by a wavelength chosen at random from the three kinds used. Each wavelength had seven luminance levels in the range of 110 to 3900cd/m2. Results: Migraine patients complained of uncomfortable glare more frequently than the control patients for all of the wavelengths employed. The discomfort glare of wavelength (480nm) for migraine patients was significantly greater than for the control subjects at all luminance levels (110-1860cd/m2). The discomfort glare of wavelength (550nm) for migraine patients was significantly greater than for the control subjects at luminance levels (1330 and 2650cd/m2). The discomfort glare of wavelength (610nm) for migraine patients was significantly greater than for the control subjects at luminance levels (1980cd/m2). Light stimulation with the peak wavelength (480nm) of ipRGC induced migraine attacks more frequently than extensivewavelength (550 and 610nm). The light source most frequently perceived as causing discomfort in the migraine group was the 480nm (39 cases), followed by the 550nm (4 cases) and the 610nm (3 cases). Conclusions: It is reported that migraine pain was worsened by light, even in blind patients in whom rod and cone damage had caused the loss of image formation. Light stimulation with the peak wavelength of ipRGC induced migraine attacks more frequently than extensive-wavelength (550 and 610nm). We determined that migraines were easily induced by the peak wavelength (480nm) of ipRGC, though not in the case of blind migraine patients. These results confirm that ipRGC are involved in the triggering of migraine attacks by light.

OR4 The Selective Cannabinoid Type-2 Receptor Agonist, JWH-133, Abolishes Mechanical Allodynia in a Model of Post-Traumatic Headache C.B. Macolino1, A.L. Tyburski1, B.K. Albertson1, D.C. Hooper2, M.B. Elliott1 1

Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA; 2Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.

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IHC 2013 Program Abstracts Objectives: The potential therapeutic mechanisms of a selective cannabinoid type-2 receptor agonist compared to a CGRP antagonist and triptan agent in a model of posttraumatic headache will be discussed. The use of rat and mouse models of post-traumatic headache to study sensitization of the trigeminovascular system will also be examined.

Conclusions: CB2R agonist treatment in an in vivo model of head trauma modulates nociception and peptidergic synaptogenesis. CB2R stimulation probably works through immune mechanisms; direct neuronal mechanisms may also be involved.

OR5 Background: Post-traumatic headache (PTH) is a prominent symptom of a concussion and prevalent among patients with mild and moderate traumatic brain injury. The cannabinoid type-2 receptor (CB2R) has an anti-nociceptive role in neuropathic and inflammatory pain models; but, until now, modulation of the CB2R has not been evaluated as a potential therapy for PTH. CB2R activation (unlike CB type-1 receptor activation), is not associated with psychoactive effects, making it an ideal therapeutic target. The mechanism of the CB2R-mediated anti-nociceptive response is unclear. Methods: A CB2R agonist (JWH-133 at 1 mg/kg) was compared to a triptan (Sumatriptan), a CGRP antagonist (MK8825), and saline in a model of controlled cortical impact (CCI) injury. CCI was induced in wild-type and CB2R knockout mice with and without treatment with the CB2R agonists (JWH-133 or 0-1966), or a CB2R antagonist (SR144528). Craniotomy and incision-only mice were included as controls. Baseline and weekly periorbital and paw von Frey (mechanical) allodynia testing were performed for up to four weeks post-injury. CGRP immunoreactive trigeminal ganglia cells and growth-associated protein (GAP-43) in the trigeminal nucleus caudalis (TNC) were determined using immunohistochemistry and western blot. Blood-brain-barrier (BBB) permeability was evaluated using sodium fluorescein (NaF) (BBB disruption is a possible mechanism contributing to sensitization). Intracellular adhesion molecule (ICAM) mRNA, and tumor necrosis factor-alpha (TNF-a) mRNA in vehicle and CB2-treated groups were measured using qRT-PCR. Results: Cortical injury causes a significant reduction in periorbital and forepaw von Frey mechanical thresholds (p