Effects of Placebo Administration on Immune Mechanisms and Relationships With Central Endogenous Opioid Neurotransmission

Authors

Alan Prossin
Alisa Koch
Phillip Campbell
Geoffroy Laumet
Christian S Stohler
Robert Dantzer
Jon-Kar Zubieta

Publication Date

2-1-2022

Journal

Molecular Psychiatry

Abstract

Behavioral conditioning and expectation can have profound impact on animal and human physiology. Placebo, administered under positive expectation in clinical trials, can have potent effects on disease pathology, obscuring active medications. Emerging evidence suggests placebo-responsive neurotransmitter systems (e.g., endogenous opioid) regulate immune function by manipulating inflammatory proteins including IL-18, a potent pro-inflammatory, nociceptive cytokine implicated in pathophysiology of various diseases. Validation that neuroimmune interactions involving brain μ-opioid receptor (MOR) activity and plasma IL-18 underlie placebo analgesic expectation could have widespread clinical applications. Unfortunately, current lack of mechanistic clarity obfuscates clinical translation. To elucidate neuroimmune interactions underlying placebo analgesia, we exposed 37 healthy human volunteers to a standardized pain challenge on each of 2 days within a Positron Emission Tomography (PET) neuroimaging paradigm using the MOR selective radiotracer,

Keywords

Analgesics, Analgesics, Opioid, Brain, Humans, Interleukin-18, Neurotransmitter Agents, Opioid Peptides, Pain, Positron-Emission Tomography, Receptors, Opioid, mu, Synaptic Transmission

DOI

10.1038/s41380-021-01365-x

PMID

34716408

PMCID

PMC9054677

PubMedCentral® Posted Date

10-29-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes