Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study
August
Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study
Vilfredo De Pascalis 0 1 2
Paolo Scacchia 0 1 2
0 La Sapienza University of Rome , Rome , Italy
1 Funding: This study was supported by an annual grant (Ricerche Universitarie, 2015-prot. C26A15RC5R) from the "La Sapienza" University of Rome
2 Editor: Alexandra Key, Vanderbilt University , UNITED STATES
We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas known to reflect the ongoing pain experience.
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OPEN ACCESS
Data Availability Statement: All relevant data are
within the paper and its Supporting Information files.
Competing Interests: The authors have declared
that no competing interests exist.
Introduction
Human pain is a potent stressor with immediate relevance to survival and is believed to be a
multi-faceted protective experience involving the activity of sensory-discriminative,
affectiveemotional, attentional-cognitive, behavioral and social learning systems [
1–3
]. Multiple
psychological factors have been suggested to modulate the magnitude of pain, i.e., past experience
[
4, 5
], classical conditioning [
6–13
], suggestibility [
14, 15
], expectancy [16], and ritualistic
therapeutic acts [
14, 17, 18
]. This type of modulation is believed to happen through a top-down
neurophysiological process that, when activated by one or more of the above mentioned
factors, may produce neurophysiological changes that affect pain perception. The use of placebos
and hypnosis represents two ways of how the top-down control can modulate pain perception,
but the research of placebo and hypnosis often follows two separate tracks and their
neurobiological similarities and differences are yet not fully understood. We have known, for a long
time, that hypnotic analgesia is not a variant on placebo analgesia since highly hypnotizable
individuals report feeling less pain during hypnosis than during placebo condition [
19
],
suggesting that the effects of placebo and hypnosis analgesia are at least in part separate processes.
A recent literature review on brain activity changes to placebo and hypnotic analgesia has
highlighted similarities and differences between these two treatments [
20
]. First, these
treatments produce similar changes in the activity of a number of brain regions labeled as pain
network (i.e., somatosensory cortex, ACC, insula, thalamus, and prefrontal cortex). The activation
of prefrontal cortex is necessary for cognitive evaluation and plays a leading role during both
placebo and hypnotic analgesia treatments [
21–24
]. Pain relief elicited through these
treatments are mediated by dopaminergic activity in the prefrontal cortex [
25–28
] and caused by
changes in expectation [
29, 30
]. Second, the major differences between these two treatments lie
in the fact that placebo analgesia produces functional changes in several parts of the limbic
system (i.e., amygdala, hypothalamus and hippocampus, periaqueductal gray, nucleus
accum (...truncated)