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.

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

BENEDETTI, Fabrizio;AMANZIO, Martina;
2011

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.
PSYCHOPHARMACOLOGY
213
4
791
797
Benedetti F; Amanzio M; Thoen W
File in questo prodotto:
File Dimensione Formato  
Psychopharmacology 2011 213 791 797.pdf

non disponibili

Tipo di file: PDF EDITORIALE
Dimensione 158.28 kB
Formato Adobe PDF
158.28 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Psychopharmacology-amanzio-PP_4aperto.pdf

embargo fino al 01/12/2012

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 296.18 kB
Formato Adobe PDF
296.18 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/131235
Citazioni
  • ???jsp.display-item.citation.pmc??? 18
  • Scopus 44
  • ???jsp.display-item.citation.isi??? 43
social impact