Alcohol hangover headache is one of the most common types of headache, yet the mechanism of how ethanol causes headache pain is unknown. Both migraine sufferers and non migraineurs experience hangover headache, but migraine sufferers experience more severe hangover headaches with less alcohol consumption. Hangover headache (veisalgia cephalgia) or delayed alcohol induced headache occurs from four to twenty four hours after the end of drinking and can cause migraine-like symptoms including unilateral throbbing pain with photophobia in migraineurs. 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.
A chronic headache model was used to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.
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 the model. Since adenosine accumulation is a result of acetate formation, an adenosine antagonist that blocked hypersensitivity was administered.
Signaling cascades downstream of acetate can promote pain. Acetate increases adenosine in many tissues, including the brain. The adenosine receptor antagonist, caffeine, administered after ethanol, blocked the nociceptive behaviors associated with ethanol. This suggests that adenosine contributes to ethanol induced hypersensitivity. Caffeine and ketorolac are used to treat hangover symptoms in humans. Non-steroidal anti-inflammatory drugs (ketorolac) alleviate the headache pain associated with alcohol hangovers and caffeine is indicated to ease other hangover symptoms, including fatigue and malaise.
The study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction.