| Objective Recurrent migraine is a neurovascular headache that leads to mostdisabling disorders accompanied with various manifestations including cutaneousallodynia within acute pain and pain-free phases, referring to the perception of pain inresponse to an innocuous stimulus. It is now well known that neuropeptides such ascalcitonin gene-related peptide (CGRP) have been associated with trigeminovascularnociceptive mechanisms via dural vasodilation and neurogenic inflammation. Mostmodels of experimental migraine used a normal animal to reflect migraine symptoms.Our focus here is the development of an animal model for recurrent migraine tomimic repetitive and episodic activation on the dural nociceptor in migraineurs. Wedeveloped a model wherein a bipolar stimulating electrode is placed onto the duralsurface, allowing successive electrical stimuli to be administered over the dura inconscious rats. In this study, we hypothesized that repetitive dural electricalstimulations could trigger persistent nociceptive behavioral and pathophysiologicalresponses that resemble a common manifestation of migraine in humans. We reportthat our model exhibits a prolonged mechanical allodynia and thermal hyperalgesialasting for1week after3times electrical stimulations on dura mater in awake andfreely moving rats. Repetitive dural electrical stimulations also induced elevatedCGRP expression, a biomarker of migraine in neurons of the trigeminal ganglion,trigeminal nucleus caudalis and thalamic ventral posteromedial nucleus. While we arenot the first to apply the dural electrical stimulation to conscious rats, we are the firstto present the current method for repetitive electrical stimulation on dura mater inconscious rats. |
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