Non-Invasive Dural Stimulation in Mice: A Novel Preclinical Model of Migraine

item.page.doi
Abstract

Background Migraine is characterized by a collection of neurological symptoms in the absence of injury or damage. However, several common preclinical migraine models require significant damage to the skull to stimulate the dura mater, the likely source of afferent signaling leading to head pain. The goal of this study was to determine whether dural stimulation can be performed in mice using an injection that does not cause injury or damage. Methods Using mice, injections of stimuli were administered to the dura mater through the soft tissue at the intersection between the lambdoidal and sagittal sutures. This technique did not require a permanent cannula nor did it cause damage to the skull or dura. Following injection of noxious stimuli, migraine-like behaviors were measured including cutaneous allodynia and facial grimace. The retrograde tracer fluorogold was applied onto the dura using the same injection technique to label trigeminal ganglion cell bodies, which were then testing in vitro using patch-clamp electrophysiology. Results Dural injection of allyl-isothiocyanate, low pH, interleukin-6, or inflammatory soup but not vehicles, led to cephalic/extracephalic allodynia. Facial grimace responses were also observed with allyl-isothiocyanate, pH 6.0, and interleukin-6. Stimulation with interleukin-6 causes priming to normally subthreshold pH 7.0 stimulation of the dura following resolution of the initial interleukin-6 behavior. Systemic injection of sumatriptan at the time of dural stimulation with inflammatory soup decreased the resulting cutaneous hypersensitivity. Trigeminal ganglion cell bodies retrogradely labeled from the dura had low pH-evoked currents similar to those generated by acid-sensing ion channels. Conclusion Non-invasive dural stimulation in mice can be used as a model of migraine in the absence of injury.

Description
Due to copyright restrictions and/or publisher's policy full text access from Treasures at UT Dallas is not available. UTD affiliates may be able to acquire a copy through Interlibrary Loan by using the link to UTD ILL.
EPUB version of article is freely available on the website. Use the DOI address below.
Keywords
Dura mater, Mice, Meninges, Headache, Migraine, Interleukin-6, Trigeminal nerve, Pain, Physiology, Pathological, Nociceptive pain
item.page.sponsorship
National Institutes of Health (NS072204)
item.page.rights
©2018 International Headache Society
Citation