Abstract Details

Title Recurrent Episodic Cortical Spreading Depressions Induce Trigeminal Allodynia and Anxiety Behavior

Topic Headache

Presentation(s) S20 - Headache Imaging and Physiology and Episodic Syndromes Associated with Migraine (4:25 PM-4:36 PM)

Poster/Presentation
Number 006

Background CSD is an intense depolarization propagating at a rate of 2-5 mm/min and the electrophysiological culprit responsible for migraine aura. Cutaneous allodynia, anxiety, and cognitive disturbances can accompany migraine, but their mechanisms are unknown.

Objective We examined a role for cortical spreading depression (CSD) in migraine related comorbidities.

Design/Methods Unilateral single event optogenetic CSDs were induced non-invasively every other day for two weeks in male and female transgenic mice. CSD was detected by optical intrinsic signal imaging and identified as a characteristic change in reflectance traveling across the cortical surface coincident with propagating oligemia. Behavioral testing was performed 24-72 hours after the last CSD. Mechanical allodynia of the periorbital and hindpaw regions was tested using von Frey monofilaments. Anxiety and working memory were tested with open field and Y maze respectively.

Results

Recurrent episodic CSDs significantly reduced periorbital mechanical pain thresholds compared with sham mice (p<0.001). Despite unilateral CSD inductions, the mechanical force threshold for periorbital nocifensive behavior did not differ between the right and left side suggesting bilateral allodynia. There was a significant main effect of sex on trigeminal mechanical pain thresholds with female mice showing lower thresholds than males (p=0.025). In contrast, hindpaw mechanical sensitivity did not differ between sham and CSD groups (p=0.149), or between males and females (p=0.607). In an open field, mice with episodic CSDs spent more time clinging to the walls (i.e. thigmotaxis), suggesting anxiety behavior (p=0.015). There was a significant main effect of sex on thigmotaxis scores (p=0.027) as well. There was no difference in Y maze testing between CSD and sham mice.

Conclusions

These data support a role for recurrent CSD in migraine related trigeminal allodynia and anxiety, with evidence for sexual dimorphism using a non-invasive model.

Authors/Disclosures
Andrea Harriott, MD (Massachusetts General Hospital) PRESENTER	Dr. Harriott has received personal compensation for serving as an employee of Abbvie. Dr. Harriott has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Dr. Harriott has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Headache Cooperative of New England. The institution of Dr. Harriott has received research support from Electrocore. Dr. Harriott has a non-compensated relationship as a Author agreement with Abbvie that is relevant to AAN interests or activities. Dr. Harriott has a non-compensated relationship as a Researcher/Receipt of drug with Praxis that is relevant to AAN interests or activities.
David Y. Chung, MD (Massachusetts General Hospital)	Dr. Chung has received research support from NIH/NINDS. Dr. Chung has received research support from The Aneurysm and AVM Foundation.
	No disclosure on file
Tao Qin	No disclosure on file
Cenk Ayata, MD (Massachusetts General Hospital)	Dr. Ayata has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quris. Dr. Ayata has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurelis. The institution of Dr. Ayata has received research support from NIH. The institution of Dr. Ayata has received research support from Takeda. The institution of Dr. Ayata has received research support from Neurelis.

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