title: Ethanol and pain sensitivity: effects in healthy subjects using an acute pain paradigm.
abstract: BACKGROUND
  The primary objective of this study was to determine whether healthy subjects without a history of heavy alcohol use or a family history of alcoholism exhibit a concentration-dependent analgesic effect of ethanol. In a preliminary fashion, we also compared this sample to a group of subjects with a strong positive family history for alcoholism (FHP) to test the secondary hypothesis that FHP individuals will be more sensitive to the analgesic effects of alcohol compared to healthy subjects who are negative for a family history of alcoholism (FHN).
  
  
  METHODS
  Forty-one healthy FHN subjects and 19 FHP subjects participated. Test days included an ethanol high concentration (breathalyzer = 0.100 g/dl), ethanol low concentration (breathalyzer = 0.040 g/dl) or placebo. The infusion of ethanol was via computerized pump to achieve a steady-state ("clamp") ethanol concentration. Noxious electrical stimulation and pain assessments were performed prior to start of placebo/ethanol infusion and at the 60-min infusion mark. The applied current was progressively increased until the pain was reported as 5 or higher on an 11-point Verbal Numeric Scale (VNS). Outcome variables included measures of pain threshold and tolerance and Visual Analog Scales of mood states.
  
  
  RESULTS
  Among FHN subjects there was a significant ethanol concentration effect on pain tolerance (F = 3.0, p = 0.05). The average change in pain stimuli required to reach a VNS of 5 or greater were (-2.4, -1.0, and 2.2 mAmps respectively) for high concentration, low concentration, and placebo. There were no ethanol concentration related differences in pain threshold. The analgesic effect of ethanol was not correlated with changes in mood states, suggesting an independent analgesic effect of the drug. A comparison of FHP to FHN subjects produced no differences on pain responses.
  
  
  CONCLUSIONS
  The findings support the hypothesis that in healthy subjects intravenous ethanol administration has a concentration effect on pain tolerance but not on pain threshold. Additional studies are planned to further elucidate the mechanisms of ethanol's analgesic effects.
authors.affiliation: Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. albert.perrino@yale.edu
authors.forename: Albert C
authors.initials: AC
authors.lastname: Perrino
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ralevski
authors.forename: Gregory
authors.initials: G
authors.lastname: Acampora
authors.forename: Javon
authors.initials: J
authors.lastname: Edgecombe
authors.forename: Diana
authors.initials: D
authors.lastname: Limoncelli
authors.forename: Ismene L
authors.initials: IL
authors.lastname: Petrakis
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics; D000698:Analgesia; D000700:Analgesics / Q000008:administration & dosage*; D001944:Breath Tests; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage* / Q000032:analysis; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D010919:Placebos
chemical_list: D000700:Analgesics; D010919:Placebos; D000431:Ethanol