Disruption of opioid-induced placebo responses by activation of cholecystokinin type-2 receptors.

Abstract

RATIONALE:

Placebos are known to induce analgesia through the activation of μ-opioid receptors in some circumstances, such as after morphine pre-conditioning, an effect that is blocked by opioid antagonists.

OBJECTIVES:

On the basis of the anti-opioid action of cholecystokinin, here we tested whether the activation of the cholecystokinin type-2 receptors abolishes opioid-induced placebo responses.

METHODS:

The activation of the cholecystokinin type-2 receptors was performed by means of the agonist pentagastrin, and placebo responses were obtained after morphine pre-conditioning in an experimental human model of pain (tourniquet technique).

RESULTS:

Opioid-induced placebo responses were completely disrupted by pentagastrin administration. In addition, a high correlation between the response to morphine and the response to placebo was found, and this correlation was completely abolished by pentagastrin.

CONCLUSION:

These results show that the cholecystokinin-2 receptor agonist, pentagastrin, has the same effect as the μ-opioid receptor antagonist, naloxone, on placebo analgesia induced by morphine pre-conditioning, which suggests that the balance between cholecystokinergic and opioidergic systems is crucial in placebo responsiveness in pain. These findings also suggest that cholecystokinin type-2 receptor hyperactivity might be present in placebo non-responders.

• Authors: Fabrizio Benedetti, Martina Amanzio, Wilma Thoen
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 213 Issue 4 Pg. 791-7 (Feb 2011) ISSN: 1432-2072 [Electronic] Germany
• PMID: 20931328 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Receptor, Cholecystokinin B
• Morphine
• Pentagastrin

Topics

• Adult
• Analgesics, Opioid (pharmacology)
• Double-Blind Method
• Female
• Humans
• Male
• Morphine (pharmacology)
• Pain (drug therapy)
• Pentagastrin (pharmacology)
• Placebo Effect
• Receptor, Cholecystokinin B (agonists, metabolism)
• Tourniquets
• Young Adult