Caffeine does not attenuate experimentally induced ischemic pain in healthy subjects

Acta Anaesthesiol Scand. 2009 Nov;53(10):1288-92. doi: 10.1111/j.1399-6576.2009.02038.x. Epub 2009 Jun 30.


Background and aims: Caffeine is likely the most widely used psychoactive substance in the world. It is also an analgesic adjuvant and has individual analgesic properties. The latter effect has been attributed to adenosine receptor antagonism, but the site of action is unknown. The aim of this study was to investigate the analgesic properties of caffeine on experimentally induced ischemic pain and to attempt to elucidate whether the site of action is central or peripheral.

Materials and methods: Seventeen healthy subjects received intravenous (i.v.) regional and systemic infusions of caffeine at 10 mg/kg or placebo in a double-blind, crossover fashion to investigate the site of action for caffeine-induced analgesia. Subjects underwent a sub-maximum effort tourniquet test. Pain scores [visual analogue scale (VAS), 0-100] were assessed every minute up to a maximum of 45 min.

Results: The sum of pain scores (SPS, accumulation of VAS scores) was attenuated neither by systemic 2405 (+/-234) nor by i.v. regional caffeine 2427 (+/-190) as compared with placebo 2442 (+/-205), P=0.99 (mean+/-SEM). Time to maximal VAS score did not differ significantly between treatments, P=0.94. There was no correlation between caffeine concentration in plasma and time to maximal pain score, or between SPS and plasma concentration.

Conclusion: Caffeine does not have an analgesic effect on ischemic pain, either by a peripheral or by a central site of action.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analgesics / administration & dosage*
  • Analgesics / blood
  • Caffeine / administration & dosage*
  • Caffeine / blood
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Pain / drug therapy*
  • Pain Measurement
  • Treatment Outcome
  • Young Adult


  • Analgesics
  • Caffeine