A new animal model of placebo analgesia: involvement of the dopaminergic system in reward learning.

In-Seon Lee,Paul Enck,Bombi Lee,Håkan Olausson,Hi-Joon Park,Younbyoung Chae

doi:10.1038/srep17140

Abstract

We suggest a new placebo analgesia animal model and investigated the role of the dopamine and opioid systems in placebo analgesia. Before and after the conditioning, we conducted a conditioned place preference (CPP) test to measure preferences for the cues (Rooms 1 and 2), and a hot plate test (HPT) to measure the pain responses to high level-pain after the cues. In addition, we quantified the expression of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and c-Fos in the anterior cingulate cortex (ACC) as a response to reward learning and pain response. We found an enhanced preference for the low level-pain paired cue and enhanced TH expression in the VTA of the Placebo and Placebo + Naloxone groups. Haloperidol, a dopamine antagonist, blocked these effects in the Placebo + Haloperidol group. An increased pain threshold to high-heat pain and reduced c-Fos expression in the ACC were observed in the Placebo group only. Haloperidol blocked the place preference effect, and naloxone and haloperidol blocked the placebo analgesia. Cue preference is mediated by reward learning via the dopamine system, whereas the expression of placebo analgesia is mediated by the dopamine and opioid systems.

Highlights

We suggest a new placebo analgesia animal model and investigated the role of the dopamine and opioid systems in placebo analgesia
These findings indicate an increase in the preference for Room 1 (LPP cue) compared to Room 2 (HPP cue) (Fig. 2b)
Rats displayed a significantly increased pain threshold when the pain was delivered after the LPP cue, indicating placebo analgesia

Summary

Introduction

We suggest a new placebo analgesia animal model and investigated the role of the dopamine and opioid systems in placebo analgesia. Recent research on the mechanism of placebo analgesia has examined the brain’s response to painful stimulation modulated by expectation or Pavlovian conditioning. Subsequent studies have investigated differential or overlapping mechanisms between conditioning and the expectation-induced placebo effect, including the endogenous opioid, cannabinoid, and dopamine systems[3,4,5]. Several studies have shown that activity is altered due to expectation-6 or conditioning-induced placebo analgesia[7] via a μ -8 or non-opioid[9] mechanism in brain regions associated with pain processing and pain modulation (e.g., the frontal cortex, cingulate cortex, insula). We used Pavlovian conditioning of neutral cues with heat pain stimulation, and hypothesized that the dopamine system was involved in the cue-learning (acquisition) phase and that the endogenous opioid system was involved in the analgesia response (expression) phase of placebo analgesia

Methods

Results

Conclusion