PubMed · 8654231
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R Orko. 1994. [Avoiding certainty while treating the pain].. https://pubmed.ncbi.nlm.nih.gov/8654231/
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Rats exposed to the stress of repeated exposure to a noxious heat source (52.5 degrees C, hot plate) exhibit stress-induced analgesia, but reduced antinociception (detected using the tail-flick test) to the administration of beta-endorphin into the periaqueductal gray region of the brain. This is accompanied by an anti-analgesic response (reduction in the stress-induced increase of tail flick latency) to doses of beta-endorphin (0.03 nmol) lower than those usually associated with antinociception. These alterations are prevented and antinociceptive potency is maintained when rats are treated with cholecystokinin (CCK) antagonists intrathecally. The potency of L-365,260 and L-364,718, selective CCK(B) and CCK(A) receptor antagonists, respectively, correlated with their apparent affinities for CCK(B) receptors, suggesting that the altered sensitivity to beta-endorphin is mediated via CCK(B) receptors.
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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.