Somatotopic Activation of Opioid Systems by Target-Directed Expectations of Analgesia

TLDR

The study induced targeted analgesic expectations on four body parts to investigate how endogenous opioid systems are activated by expectancy. Participants received capsaicin injections to produce pain, while a placebo cream and verbal suggestion of a potent anesthetic were applied to one limb, creating a spatially specific analgesic expectation. The placebo analgesic effect was confined to the treated limb and was abolished by naloxone, demonstrating that endogenous opioids mediate a spatially specific, somatotopic response linking expectation, attention, and body schema.

Abstract

We induced specific expectations of analgesia on four different parts of the body to understand how endogenous opioid systems are activated by expectancies. The left hand, right hand, left foot, and right foot were simultaneously stimulated by means of a subcutaneous injection of capsaicin, which produces a painful burning sensation. Specific expectations of analgesia were induced by applying a placebo cream on one of these body parts and by telling the subjects that it was a powerful local anesthetic. In such a way, expectancy of the anesthetic effect was directed only toward the part on which the placebo cream was applied. We found that a placebo analgesic response occurred only on the treated part, whereas no variation in pain sensitivity was found on the untreated parts. If the same experiment was performed after an intravenous infusion of the opioid antagonist naloxone, this highly spatial-specific placebo response was totally abolished, indicating that it was completely mediated by endogenous opioid systems. These findings show that a spatially directed expectation of pain reduction is capable of inducing a specific effect only on the part of the body which is the target of the expectation. Most important, this specific effect is mediated by endogenous opioids, indicating that placebo-activated opioids do not act on the entire body but only on the part where expectancy is directed. This suggests that a highly organized and somatotopic network of endogenous opioids links expectation, attention, and body schema.