Abstract Details

Title DAGLa Inhibition as a Non-invasive and Translational Model of Episodic Headache

Topic Headache

Presentation(s) Headache Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 058

Objective This study examines the role of DAGL in headache development. We investigate exogenous inhibition of DAGL as a novel route to recapitulate the clinical features of episodic headache.

Background In two models of medication overuse headache, 2-AG levels were selectively depleted in the periaqueductal grey (PAG), suggesting distinct regulation of DAGL, the main biosynthetic enzyme for 2-AG, at times of headache pain. These results led to the hypothesis that reduction of 2-AG via blockade of DAGL would induce headache-like behaviors.

Design/Methods Inhibition of DAGL was performed via injection of non-selective DAGL (DH376, 10 mg/kg, IP) and selective DAGLα (LEI106, 20 mg/kg, IP) and DAGLβ (KT109, 20mg/kg, IP) inhibitors. Following DAGL blockade, studies measured 2-AG and AEA levels via LC-MS as well as headache relevant behaviors, including periorbital and hind-paw allodynia, photophobia, anxiety-like behaviors, and the responsivity of induced pain behaviors to abortive antimigraine agents.

Results Injection of non-selective DAGL and selective DAGLα inhibitors induced facial sensitivity in 100% and ~60% of female rats, respectively, without induction of peripheral sensitivity. Induced periorbital allodynia was attenuated by administration of sumatriptan and olcegepant. Selective DAGLα inhibition induced significant photophobia, without anxiety-like behaviors or changes in voluntary movement. Analysis of AEA and 2-AG levels revealed reductions in 2-AG in the visual cortex and periaqueductal grey (PAG), without altering AEA

Conclusions These results provide evidence for the induction of headache-like pain and light sensitivity without extracephalic allodynia, thus modeling the clinical presentation of episodic headache. DAGL inhibition, which reduces the time, cost, and invasiveness of currently accepted models of headache may fill the gap left by current models of headache that largely reflect manifestations of chronic migraineurs, and it may provide an avenue to study the transition from episodic to chronic headache

Authors/Disclosures
Aidan Levine PRESENTER	Mr. Levine has received research support from University of Arizona MD/PhD Program.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Daniela Salvemini (Saint Louis University)	No disclosure on file
	No disclosure on file
	No disclosure on file

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Abstract Details