Abstract
Despite having powerful physical and emotional effects, the neurobiological mechanisms underlying placebo are poorly understood. Emerging evidence suggests placebo modulates central immune activity, effectively reducing pro-inflammatory cytokines. IL-18 is an Il-1 family cytokine secreted by activated microglia. In depression, plasma IL-18 is elevated and proportional to regional μ -opioid receptor availability (μ-OR). Within these brain regions, μ -OR availability is believed both altered in depression and pain states and proportional to placebo response. While evidence suggests similar neuro–immune interaction underlie the impact of placebo on physical and emotional states, these mechanisms have been barely examined either in animal models or in humans. Using [11C]CFN PET, we investigated the impact of placebo on plasma IL-18 and its relation to central opioid neurotransmitter responses to a standardized, sustained, pain challenge. Placebo reduced plasma IL-18 ( p r = 0.4, p Z = 6.0, p Z = 4.6, p Z = 5.8; p Z = 4.3, p Z = 4.3, p Z = 4.6, p
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