Nitroglycerine triggers triptan-responsive cranial allodynia and trigeminal neuronal hypersensitivity
PublisherOxford University Press
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AbstractCranial allodynia associated with spontaneous migraine is reported as either responsive to triptan treatment or to be predictive of lack of triptan efficacy. These conflicting results suggest that a single mechanism mediating the underlying neurophysiology of migraine symptoms is unlikely. The lack of a translational approach to study cranial allodynia reported in migraine patients is a limitation in dissecting potential mechanisms. Our objective was to study triptan-responsive cranial allodynia in migraine patients, and to develop an approach to studying its neural basis in the laboratory. Using nitroglycerine to trigger migraine attacks, we investigated whether cranial allodynia could be triggered experimentally, observing its response to treatment. Preclinically, we examined the cephalic response properties of central trigeminocervical neurons using extracellular recording techniques, determining changes to ongoing firing and somatosensory cranial-evoked sensitivity, in response to nitroglycerine followed by triptan treatment. Cranial allodynia was triggered alongside migraine-like headache in nearly half of subjects. Those who reported cranial allodynia accompanying their spontaneous migraine attacks were significantly more likely to have symptoms triggered than those that did not. Patients responded to treatment with aspirin or sumatriptan. Preclinically, nitroglycerine caused an increase in ongoing firing and hypersensitivity to intracranial-dural and extracranial-cutaneous (noxious and innocuous) somatosensory stimulation, reflecting signatures of central sensitization potentially mediating throbbing headache and cranial allodynia. These responses were aborted by a triptan. These data suggest that nitroglycerine can be used as an effective and reliable method to trigger cranial allodynia in subjects during evoked migraine, and the symptom is responsive to abortive triptan treatments. Preclinically, nitroglycerine activates the underlying neural mechanism of cephalic migraine symptoms, central sensitization, also predicting the clinical outcome to triptans. This supports a biological rationale that several mechanisms can mediate the underlying neurophysiology of migraine symptoms, with nitrergic-induced changes reflecting one that is relevant to spontaneous migraine in many migraineurs, whose symptoms of cranial allodynia are responsive to triptan treatment. This approach translates directly to responses in animals and is therefore a relevant platform to study migraine pathophysiology, and for use in migraine drug discovery. Copyright The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain.
SponsorsThis work has been supported by a donation from the Sandler Family Foundation to UCSF, start-up funds from NYU (M.R.R.), the Medical Research Council (P.R.H; MR/ P006264/1) and the Wellcome Trust (P.J.G; grant number 104033). J.R.H. was supported by a grant from the German Research Foundation (DFG; HO4369/1-1). The clinical studies were funded by the Migraine Trust (PB), and Dr. Karsan is supported by an Association of British Neurologists/Guarantors of Brain Clinical Research Training Fellowship. The clinical studies have been supported by the NIHR SLaM Biomedical Research Centre.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85059271279&doi=10.1093%2fbrain%2fawy313&partnerID=40&md5=20366f32928e6271907f83bedee1bad2; http://hdl.handle.net/10713/8624