acetate causes alcohol hangover headache in rats醋酸引起酒精宿醉头痛的老鼠.pdfVIP

Acetate Causes Alcohol Hangover Headache in Rats 1 1 2 1 Christina R. Maxwell , Rebecca Jay Spangenberg , Jan B. Hoek , Stephen D. Silberstein , Michael L. Oshinsky1* 1 Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America, 2 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America Abstract Background: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache. Methods: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats. Results: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate increased nociceptive behaviors suggesting that acetate, not acetaldehyde, accumulation results in hangover-like hypersensitivity in our model. Since adenosine accumulation is a result of acetate formation, we administered an adenosine antagonist that blocked hypersensitivity. Discussion: Our study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction. Citation: Maxwell CR, Spangenberg RJ, Hoek JB, Silberstein SD, Oshinsky ML (