Research Article: Pain Modulation in Waking and Hypnosis in Women: Event-Related Potentials and Sources of Cortical Activity

Date Published: June 1, 2015

Publisher: Public Library of Science

Author(s): Vilfredo De Pascalis, Vincenzo Varriale, Immacolata Cacace, André Mouraux.


Using a strict subject selection procedure, we tested in High and Low Hypnotizable subjects (HHs and LHs) whether treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs) during painful electric stimulation. Treatments were administered in waking and hypnosis conditions. LHs showed little differentiation in pain and distress ratings between hypoalgesia and hyperalgesia treatments, whereas HHs showed a greater spread in the instructed direction. HHs had larger prefrontal N140 and P200 waves of the SERPs during hypnotic hyperalgesia as compared to relaxation-control treatment. Importantly, HHs showed significant smaller frontocentral N140 and frontotemporal P200 waves during hypnotic hypoalgesia. LHs did not show significant differences for these SERP waves among treatments in both waking and hypnosis conditions. Source localization (sLORETA) method revealed significant activations of the bilateral primary somatosensory (BA3), middle frontal gyrus (BA6) and anterior cingulate cortices (BA24). Activity of these contralateral regions significantly correlated with subjective numerical pain scores for control treatment in waking condition. Moreover, multivariate regression analyses distinguished the contralateral BA3 as the only region reflecting a stable pattern of pain coding changes across all treatments in waking and hypnosis conditions. More direct testing showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. sLORETA in HHs revealed, for the N140 wave, that during hypnotic hyperalgesia, there was an increased activity within medial, supramarginal and superior frontal gyri, and cingulated gyrus (BA32), while for the P200 wave, activity was increased in the superior (BA22), middle (BA37), inferior temporal (BA19) gyri and superior parietal lobule (BA7). Hypnotic hypoalgesia in HHs, for N140 wave, showed reduced activity within medial and superior frontal gyri (BA9,8), paraippocampal gyrus (BA34), and postcentral gyrus (BA1), while for the P200, activity was reduced within middle and superior frontal gyri (BA9 and BA10), anterior cingulate (BA33), cuneus (BA19) and sub-lobar insula (BA13). These findings demonstrate that hypnotic suggestions can exert a top-down modulatory effect on attention/preconscious brain processes involved in pain perception.

Partial Text

Human pain is a multi-faceted protective experience involving the activity of sensory-discriminative, affective-emotional, attention-cognitive and behavioral systems [1–6]. Melzack and Casey [7] proposed that this experience reflects the mutual interaction of sensory, affective and cognitive dimensions and, thus, requires the integrated activity of a widely distributed network of neurons, extending throughout widespread areas of the brain (a neuromatrix), necessary to generate the neurosignature pattern for pain. This view implied that pain is the product of the activity of a multidimensional and distributed neural network rather than of a “brain pain centre” usually triggered by sensory inputs. This network, often referred to as the “pain matrix” (PM), is viewed as representing the activity induced by the intensity and unpleasantness of a nociceptive stimulus. However, recent studies [8] have beset the very concept of a specific pain-related network, claiming that most regions present in the PM are part of a basic nonspecific salience-detection system, activated by the occurrence of potentials threats detected for the body’s integrity, regardless of the sensory channel through which these events are conveyed [9,10]. This view has been provided suggesting that the brain responses to nociceptive stimuli, as measured using functional neuroimaging techniques (i.e., EEG, MEG, fMRI, PET), do not reflect nociceptive-specific brain activities, but, instead, brain activities equally involved in processing nociceptive and non-nociceptive salient sensory inputs. Therefore, it has been suggested that the term “pain matrix” should be used with caution, because it misleadingly implies that the recorded responses are specific for pain [9]. However, very recently, PM has been reconceptualized as a fluid system composed of several interacting networks [11]. A first-order nociceptive matrix responsible for the earliest responses to noxious stimuli (i.e., spinothalamic sensory cortices, brainstem, bilateral thalamus, posterior insula, medial parietal operculum and mid-cingulate cortex) ensures the bodily specificity of pain and is the only one whose destruction entails selective pain deficits [12]. The transition from cortical nociception to multiple attentional-affective and cognitive modulations, necessary for conscious perception of pain, requires the recruitment of a second order-network of not nociceptive-specific cortical regions including anterior cingulate cortex (ACC) [13–15], premotor cortex [16], dorsolateral prefrontal cortex (DLPFC) [17], posterior parietal, prefrontal and anterior insular areas, and cortical representations of non-painful tactile stimuli, highly aligned with nociceptive maps [18–20]. Since pain experience can be modified as a function of beliefs [21], expectations [22] and placebo [23], this new reconceptualization has suggested that this is done through the activity of third-order areas, including the orbitofrontal and perigenual/limbic networks. In this view, the neural substrate of the pain experience is conceived at progressively different levels of higher-order cortical networks, from cortical nociception to conscious experience. The role of different regions being dependent on the context in which the stimuli are delivered, has been put forward by a few investigators (eg, [24, 25]) and conscious experience called “pain” is subjected to reappraisal by internal states, feelings and beliefs prior to stabilization into memory stores.

In this paper we describe a SERP study examining the effects of hypnotic susceptibility and hypnotic suggestions on electro-cortical responses and on sensory-discriminative (pain rating) and affective-motivational (distress rating) components of pain induced by noxious electric stimulation. These measures were obtained in waking and hypnosis condition under a relaxation-control and suggestions to either increase (hyperalgesia) or decrease pain sensation (hypoalgesia). In this context, we did an attempt to validate previous pain-ERP findings to noxious electric stimulation during hypnosis [49]. We asked three main questions: 1) do high and low susceptible individuals respond differentially to the experience of pain; 2) do hypnotic suggestions influence the experience of pain; and 3) are there physiological mechanisms that differentially mediate the manner in which high and low susceptible individuals respond to these suggestions. Using sLORETA tool, the present study served to highlight brain responses and cortical regions coding for pain/distress and to evaluate if the brain pattern of pain/distress coding may change depending on the experimental treatment and/or condition. The main aim of the study was to evaluate how treatments of hypoalgesia and hyperalgesia, as compared to a relaxation-control, differentially affected subjective pain ratings and somatosensory event-related potentials (SERPs) to noxious electric stimuli in waking and hypnosis and how these differences are reflected in HH and LH participants. Source localization analysis (sLORETA method) of N100 and P200 SERP waves was used to substantiate the role of the main cortical regions sensitive to pain modulation treatments in HH and LH participants during waking and hypnosis.

The present findings describe hypnotic modulation of brain activation patterns associated with nociceptive processing. Correlation analyses distinguished BA3 activity, contralateral to the stimulation side, as the only one reflecting a stable pattern of pain coding changes across treatments in waking and hypnosis conditions. A more direct regression analysis testing also showed that hypnosis reduced the strength of the association of pain modulation and brain activity changes at BA3. The study convincingly demonstrates that hypnotic hypoalgesia is associated with reduced activity of the N140 and P200 SERP components, whereas hypnotic hyperalgesia is associated with increased activity of these components. Our source findings are among the first to clearly distinguish separate regions of the first, second, and third order pain matrices [11] as sensitive to hypoalgesia and hyperalgesia treatments during hypnosis. We suggest that treatments for reducing and increasing pain sensation were effective in pain modulation through top-down influences.