title: Acetate causes alcohol hangover headache in rats.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christina R
authors.initials: CR
authors.lastname: Maxwell
authors.forename: Rebecca Jay
authors.initials: RJ
authors.lastname: Spangenberg
authors.forename: Jan B
authors.initials: JB
authors.lastname: Hoek
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Silberstein
authors.forename: Michael L
authors.initials: ML
authors.lastname: Oshinsky
mesh_terms: D000079:Acetaldehyde / Q000009:adverse effects; D000085:Acetates / Q000737:chemistry*; D000428:Alcohol Drinking; D000435:Alcoholic Intoxication / Q000378:metabolism*; D000698:Analgesia; D000818:Animals; D002908:Chronic Disease; D000431:Ethanol / Q000009:adverse effects; D006261:Headache / Q000139:chemically induced*; D006967:Hypersensitivity; D007249:Inflammation; D008297:Male; D009619:Nociceptors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014110:Touch
chemical_list: D000085:Acetates; D000431:Ethanol; D000079:Acetaldehyde