Pain as a reward: changing the meaning of pain from negative to positive co-activates opioid and cannabinoid systems

Pain. 2013 Mar;154(3):361-367. doi: 10.1016/j.pain.2012.11.007. Epub 2012 Nov 21.


Pain is a negative emotional experience that is modulated by a variety of psychological factors through different inhibitory systems. For example, endogenous opioids and cannabinoids have been found to be involved in stress and placebo analgesia. Here we show that when the meaning of the pain experience is changed from negative to positive through verbal suggestions, the opioid and cannabinoid systems are co-activated and these, in turn, increase pain tolerance. We induced ischemic arm pain in healthy volunteers, who had to tolerate the pain as long as possible. One group was informed about the aversive nature of the task, as done in any pain study. Conversely, a second group was told that the ischemia would be beneficial to the muscles, thus emphasizing the usefulness of the pain endurance task. We found that in the second group pain tolerance was significantly higher compared to the first one, and that this effect was partially blocked by the opioid antagonist naltrexone alone and by the cannabinoid antagonist rimonabant alone. However, the combined administration of naltrexone and rimonabant antagonized the increased tolerance completely. Our results indicate that a positive approach to pain reduces the global pain experience through the co-activation of the opioid and cannabinoid systems. These findings may have a profound impact on clinical practice. For example, postoperative pain, which means healing, can be perceived as less unpleasant than cancer pain, which means death. Therefore, the behavioral and/or pharmacological manipulation of the meaning of pain can represent an effective approach to pain management.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arm / blood supply
  • Attitude to Health
  • Cannabinoid Receptor Antagonists / adverse effects
  • Cannabinoid Receptor Antagonists / pharmacokinetics
  • Culture
  • Double-Blind Method
  • Female
  • Humans
  • Ischemia / complications
  • Male
  • Naltrexone / adverse effects
  • Naltrexone / pharmacokinetics
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / pharmacokinetics
  • Opioid Peptides / physiology*
  • Pain / etiology
  • Pain / psychology*
  • Persuasive Communication*
  • Physical Endurance
  • Piperidines / adverse effects
  • Piperidines / pharmacokinetics
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacokinetics
  • Receptors, Cannabinoid / physiology*
  • Reward*
  • Rimonabant
  • Suggestion
  • Time Factors
  • Young Adult


  • Cannabinoid Receptor Antagonists
  • Narcotic Antagonists
  • Opioid Peptides
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Naltrexone
  • Rimonabant