Dose-related effects of oral acetaminophen on cold-induced pain: a double-blind, randomized, placebo-controlled trial

Clin Pharmacol Ther. 1998 Mar;63(3):379-83. doi: 10.1016/S0009-9236(98)90169-2.


The cold-pressor test is a widely used pain-induction model in humans. This method has been shown to be a sensitive measure for detecting opioid analgesia. However, nonsteroidal anti-inflammatory drugs have not produced consistent analgesic effects with use of this model. The analgesic effect of acetaminophen (INN, paracetamol) on cold pressor-induced pain has not been reported by other investigators. In this study, a double-blind, randomized, placebo-controlled design was used to evaluate the dose-related effects of oral acetaminophen on cold pressor-induced pain in 18 normal healthy human subjects. We observed dose-related analgesic activity of oral acetaminophen using the cold pressor-induced pain model in these subjects. There were statistically significant main effects of both dose and time (pain and bothersomeness ratings decreased with increasing drug dose and increased over time). In pairwise comparisons only the contrast between the highest dose of acetaminophen (1000 mg) and placebo reached statistical significance. Results from our study suggest that the cold-pressor method may have clinical value in evaluating nonopioid analgesic agents.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / pharmacology*
  • Administration, Oral
  • Adult
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / pharmacology*
  • Analysis of Variance
  • Cold Temperature
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Pain / drug therapy*
  • Pain / etiology
  • Reference Values
  • Treatment Outcome


  • Analgesics, Non-Narcotic
  • Acetaminophen