Abstract
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.
Highlights
IntroductionMigraine headache is thought to be the result of abnormal activation and sensitization (Noseda and Burstein, 2013), or the perception of activation (Akerman et al, 2011; Goadsby et al, 2017), of trigeminal primary afferents innervating the nociceptive producing dural vasculature and their central projections to the medullary dorsal horn and upper cervical spinal cord (Noseda and Burstein, 2013; Goadsby et al, 2017)
Nitroglycerine triggers cranial allodynia that responds to abortive treatment Visit 1 Of the 53 subjects, 44 had migraine headache triggered with nitroglycerine and nine did not, one had left cranial allodynia triggered without moderate-severe headache (Case 12); an 83% triggering rate
Whilst the sample size of human subjects exposed to nitroglycerine here was not sufficient for extensive subgroup analysis of migraine subtypes, it is clear that nitroglycerine can acutely provoke cranial allodynia in humans and this is consistent with patient self-reports of acute allodynia associated with episodic migraine attacks and the lack of association of the presence of allodynia with effective treatment response (Cady et al, 2009)
Summary
Migraine headache is thought to be the result of abnormal activation and sensitization (Noseda and Burstein, 2013), or the perception of activation (Akerman et al, 2011; Goadsby et al, 2017), of trigeminal primary afferents innervating the nociceptive producing dural vasculature and their central projections to the medullary dorsal horn and upper cervical spinal cord (Noseda and Burstein, 2013; Goadsby et al, 2017) Sensitization of these dural-responsive trigeminovascular neurons, which receive inputs from facial cutaneous areas, is thought to cause extracranial facial hypersensitivity manifesting as cutaneous allodynia and hyperalgesia in migraine patients (Burstein et al, 2000). Other phenotypic symptoms, such as cranial allodynia, have not been captured previously in such studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
