Effects of placebo administration on immune mechanisms and relationships with central endogenous opioid neurotransmission.

Autor: Prossin A; Department of Psychiatry and Behavioral Sciences, University of Texas McGovern Medical School, Houston, TX, USA. alan.prossin@uth.tmc.edu.; Translational Imaging Center, Houston Methodist Research Institute, Weill Cornell College of Medicine, Houston, TX, USA. alan.prossin@uth.tmc.edu., Koch A; Department of Internal Medicine, Division of Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA., Campbell P; Department of Internal Medicine, Division of Rheumatology, University of Michigan Medical School, Ann Arbor, MI, USA., Laumet G; Department of Physiology, Michigan State University, East Lansing, MI, USA., Stohler CS; College of Dental Medicine, Columbia University, New York, NY, USA., Dantzer R; Department of Symptom Research, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zubieta JK; Department of Psychiatry, John T Mather Memorial Hospital, Northwell Health, Port Jefferson, NY, USA.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2022 Feb; Vol. 27 (2), pp. 831-839. Date of Electronic Publication: 2021 Oct 29.
DOI: 10.1038/s41380-021-01365-x
Abstrakt: 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, 11 C-Carfentanil (CFN). Each day volunteers received an intervention (placebo under analgesic expectation or no treatment), completed PET scanning, and rated their pain experience. MOR BP ND parametric maps were generated from PET scans using standard methods. Results showed placebo reduced plasma IL-18 during pain (W 74  = -3.7, p < 0.001), the extent correlating with reduction in pain scores. Placebo reduction in IL-18 covaried with placebo-induced endogenous opioid release in the left nucleus accumbens (T 148  = 3.33; p uncorr  < 0.001) and left amygdala (T 148  = 3.30; p uncorr  < 0.001). These findings are consistent with a modulating effect of placebo (under analgesic expectation in humans) on a potent nociceptive, pro-inflammatory cytokine (IL-18) and underlying relationships with endogenous opioid activity, a neurotransmitter system critically involved in pain, stress, and mood regulation.
(© 2021. The Author(s).)
Databáze: MEDLINE
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