Cranial
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.