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.
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Acknowledgments
This work was supported by grants from the Istituto San Paolo di Torino and the Regione Piemonte (Turin, Italy) and from the Volkswagen Foundation (Hannover, Germany). The experiments of the present study comply with the current laws of the country in which they were performed (Italy).
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The authors have no conflicts of interest.
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Benedetti, F., Amanzio, M. & Thoen, W. Disruption of opioid-induced placebo responses by activation of cholecystokinin type-2 receptors. Psychopharmacology 213, 791–797 (2011). https://doi.org/10.1007/s00213-010-2037-y
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DOI: https://doi.org/10.1007/s00213-010-2037-y