Abstract
Placebo exhibits beneficial effects on pain perception in human experimental studies. Most of these studies demonstrate that placebo significantly decreased neural activities in pain modulatory brain regions and pain-evoked potentials. This study examined placebo analgesia-related effects on spontaneous brain oscillations. We examined placebo effects on four order-fixed 20-min conditions in two sessions: isotonic saline-induced control conditions (with/without placebo) followed by hypertonic saline-induced tonic muscle pain conditions (with/without placebo) in 19 subjects using continuous electroencephalography (EEG) recording. Placebo treatment exerted significant analgesic effects in 14 placebo responders, as subjective intensity of pain perception decreased. Frequency analyses were performed on whole continuous EEG data, data during pain perception rating and data after rating. The results in the first two cases revealed that placebo induced significant increases and a trend toward significant increases in the amplitude of alpha oscillation during tonic muscle pain compared to control conditions in frontal-central regions of the brain, respectively. Placebo-induced decreases in the subjective intensity of pain perception significantly and positively correlated with the increases in the amplitude of alpha oscillations during pain conditions. In conclusion, the modulation effect of placebo treatment was captured when the pain perception evaluating period was included. The strong correlation between the placebo effect on reported pain perception and alpha amplitude suggest that alpha oscillations in frontal-central regions serve as a cortical oscillatory basis of the placebo effect on tonic muscle pain. These results provide important evidence for the investigation of objective indicators of the placebo effect.
Highlights
Placebo effects on pain perception were characterized using numerous hemodynamic (e.g., functional magnetic resonance imaging and positron emission tomography (PET)) and electrophysiological (e.g., electroencephalography (EEG) and magnetoencephalography (MEG)) in previous studies (Wager et al, 2004, 2006; Lorenz et al, 2005; Zubieta et al, 2005; Placebo Analgesia Changes Alpha OscillationsScott et al, 2008; Tracey, 2010)
The present study described an active placebo effect on electrophysiological alpha oscillations during 20 min of tonic muscle pain
The decreases in the subjective intensity of pain perception to noxious stimulation after placebo treatment and the increases in the amplitude of alpha oscillation were significantly correlated. These findings suggest that placebo modulation in cognitive appraisal/experience of tonic muscle pain were effectively indexed by electrophysiological alpha oscillations, which served as additional evidence for the expectancy-based placebo mechanism (Wager et al, 2004; Zubieta et al, 2005; Scott et al, 2007; Atlas and Wager, 2012)
Summary
Placebo effects on pain perception were characterized using numerous hemodynamic (e.g., functional magnetic resonance imaging (fMRI) and positron emission tomography (PET)) and electrophysiological (e.g., electroencephalography (EEG) and magnetoencephalography (MEG)) in previous studies (Wager et al, 2004, 2006; Lorenz et al, 2005; Zubieta et al, 2005; Placebo Analgesia Changes Alpha OscillationsScott et al, 2008; Tracey, 2010). Laser-evoked potentials (LEPs) are one of the best tools to assess the function of nociceptive pathways in physiological and clinical settings (Bromm and Treede, 1991; Iannetti et al, 2001), and LEPs were used in previous studies to investigate placebo analgesia (Wager et al, 2006; Watson et al, 2007). These studies demonstrated a clear decrease in P2 amplitude using LEPs (Wager et al, 2006), which suggests that the placebo treatment affected early nociceptive processing (e.g., attention and affect). Hypertonic saline was continuously infused to maintain a relatively stable pain sensation based on real-time feedback of subjective pain intensity (Stohler, 1992)
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