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Abstract Details

DAGLa Inhibition as a Non-invasive and Translational Model of Episodic Headache
Headache Posters (7:00 AM-5:00 PM)
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.
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.
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.
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
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
Aidan Levine
Mr. Levine has received research support from University of Arizona MD/PhD Program.
Erika Liktor-Busa (University of Arizona Department of Pharmacology) Erika Liktor-Busa has nothing to disclose.
Kelly Karlage (University of Arizona, Dept of Pharmacology) Kelly Karlage has nothing to disclose.
Luigino Antonio Giancotti (2Department of Pharmacology and Physiology, Henry and Amelia Nasrallah Center fo) Luigino Antonio Giancotti has nothing to disclose.
Daniela Salvemini (Saint Louis University) Daniela Salvemini has nothing to disclose.
Todd Vanderah (University of Arizona) Todd Vanderah has nothing to disclose.
Tally Largent-Milnes Tally Largent-Milnes has received personal compensation for serving as an employee of Expesicor. Tally Largent-Milnes has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Expesicor. Tally Largent-Milnes has received intellectual property interests from a discovery or technology relating to health care.