Pierre Rainville

Brain mechanisms of pain affect and pain modulation.

Recent animal studies reveal ascending nociceptive and descending modulatory pathways that may contribute to the affective-motivational aspects of pain and play a critical role in the modulation of pain. In humans, a reliable pattern of cerebral activity occurs during the subjective experience of pain. Activity within the anterior cingulate cortex and possibly in other classical limbic structures, appears to be closely related to the subjective experience of pain unpleasantness and may reflect the regulation of endogenous mechanisms of pain modulation.

Dissociation of sensory and affective dimensions of pain using hypnotic modulation.

Understanding the complex nature of pain perception requires the ability to separately analyze its psychological dimensions and their interaction, and relate them to specific variables and responses. The present study, therefore, attempted to selectively modulate the sensory and affective dimensions of pain, using a cognitive intervention, and to assess the possible relationship between these psychological dimensions of pain and changes in physiological responses to the noxious stimuli. In three experiments, normal subjects trained in hypnosis rated pain intensity and pain unpleasantness produced by a tonic heat-pain stimulus (1-min immersion of the hand in 45.0-47.5 degrees C water). Two experiments were designed to test hypnotic suggestions to decrease (Experiment one (Section 2.5.1)), or increase and decrease (Experiment two (Section 2.5.2)) pain affect. Suggestions in Experiment three (Section 2.5.3) were directed towards an increase or decrease in pain sensation. In Experiments one and two (Sections 2.5.1 and 2.5.2), the significant modulation in pain unpleasantness ratings was largely independent of variations in perceived pain intensity. Moreover, in Experiment two (Section 2.5.2), there was a significant correlation between the stimulus-evoked heart-rate increase and ratings of pain unpleasantness, but not of pain intensity, suggesting a direct functional interaction between pain affect and autonomic activation. In Experiment three (Section 2.5.3), suggestions to modulate the sensory aspect of pain produced significant modulation of pain intensity ratings, with secondary changes in pain unpleasantness ratings. Hypnotic susceptibility (Stanford Hypnotic Susceptibility Scale form A) was specifically correlated to pain unpleasantness modulation in Experiment two (Section 2.5.2) and to pain intensity modulation in Experiment three (Section 2.5.3), suggesting that this factor relates to the primary process toward which hypnotic suggestions are directed. The specific pain dimension on which hypnotic suggestions act depends on the content of the instructions and is not a characteristic of hypnosis itself. Results are consistent with a successive-stage model of pain perception (e.g. Wade JB, Dougherty LM, Archer CR, Price DD. Assessing the stages of pain processing: a multivariate analytical approach. Pain 1996;68:157-167) which provides a conceptual framework necessary to study the cerebral representation of pain perception.

Cerebral Mechanisms of Hypnotic Induction and Suggestion

The neural mechanisms underlying hypnotic states and responses to hypnotic suggestions remain largely unknown and, to date, have been studied only with indirect methods. Here, the effects of hypnosis and suggestions to alter pain perception were investigated in hypnotizable subjects by using positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) and electroencephalographic (EEG) measures of brain electrical activity. The experimental conditions included a restful state (Baseline) followed by hypnotic relaxation alone (Hypnosis) and by hypnotic relaxation with suggestions for altered pain unpleasantness (Hypnosis-with-Suggestion). During each scan, the left hand was immersed in neutral (35C) or painfully hot (47C) water in the first two conditions and in painfully hot water in the last condition. Hypnosis was accompanied by significant increases in both occipital rCBF and delta EEG activity, which were highly correlated with each other (r = 0.70, p < 0.0001). Peak increases in rCBF were also observed in the caudal part of the right anterior cingulate sulcus and bilaterally in the inferior frontal gyri. Hypnosis-related decreases in rCBF were found in the right inferior parietal lobule, the left precuneus, and the posterior cingulate gyrus. Hypnosis-with-suggestions produced additional widespread increases in rCBF in the frontal cortices predominantly on the left side. Moreover, the medial and lateral posterior parietal cortices showed suggestion-related increases overlapping partly with regions of hypnosis-related decreases. Results support a state theory of hypnosis in which occipital increases in rCBF and delta activity reflect the alteration of consciousness associated with decreased arousal and possible facilitation of visual imagery. Frontal increases in rCBF associated with suggestions for altered perception might reflect the verbal mediation of the suggestions, working memory, and top-down processes involved in the reinterpretation of the perceptual experience. These results provide a new description of the neurobiological basis of hypnosis, demonstrating specific patterns of cerebral activation associated with the hypnotic state and with the processing of hypnotic suggestions.

A Psychophysical Comparison of Sensory and Affective Responses to Four Modalities of Experimental Pain

It is generally accepted that the sensory and affective components of pain may be differentially associated with various acute and chronic diseases, and that some treatment regimens are best directed toward certain aspects of the pain experience. In addition, experimental animal models have been described that presume to assess either the sensory-discriminative aspects of phasic pain or the affective responses associated with tonic pain. The present psychophysical experiment directly compares the perceived intensity and unpleasantness of sensations evoked by four types of experimental noxious stimuli: contact heat, electric shock, ischemic exercise, and cold-pressor pain. A novel pain measurement technique is described that incorporates unbounded magnitude-estimation/category scales; this technique allows precise ratio responses, while minimizing within- and between-subject variability. We observe that, relative to the perceived intensity of the individual stimuli, subjects consistently differentiate among the degrees of unpleasantness evoked by the four stimulus modalities. Ischemic exercise and cold-pressor pain evoke higher estimates of unpleasantness, and thus may better mimic the pain of chronic disease. The relative unpleasantness produced by contact heat is significantly less than that of the other modalities tested, and therefore contact heat stimuli may be ideally suited for assessing sensory-discriminative aspects of pain perception. Possible neurophysiological mechanisms underlying the observed differences in perceived unpleasantness are discussed in relation to the growing body of literature concerning tonic and phasic pain stimuli.

Hypnosis Modulates Activity in Brain Structures Involved in the Regulation of Consciousness

The notion of consciousness is at the core of an ongoing debate on the existence and nature of hypnotic states. Previously, we have described changes in brain activity associated with hypnosis (Rainville, Hofbauer, Paus, Duncan, Bushnell, & Price, 1999). Here, we replicate and extend those findings using positron emission tomography (PET) in 10 normal volunteers. Immediately after each of 8 PET scans performed before (4 scans) and after (4 scans) the induction of hypnosis, subjects rated their perceived level of mental relaxation and mental absorption, two of the key dimensions describing the experience of being hypnotized. Regression analyses between regional cerebral blood flow (rCBF) and self-ratings confirm the hypothesized involvement of the anterior cingulate cortex (ACC), the thalamus, and the ponto-mesencephalic brainstem in the production of hypnotic states. Hypnotic relaxation further involved an increase in occipital rCBF that is consistent with our previous interpretation that hypnotic states are characterized by a decrease in cortical arousal and a reduction in cross-modality suppression (disinhibition). In contrast, increases in mental absorption during hypnosis were associated with rCBF increases in a distributed network of cortical and subcortical structures previously described as the brains attentional system. These findings are discussed in support of a state theory of hypnosis in which the basic changes in phenomenal experience produced by hypnotic induction reflect, at least in part, the modulation of activity within brain areas critically involved in the regulation of consciousness.

A Biopsychosocial Formulation of Pain Communication.

We present a detailed framework for understanding the numerous and complicated interactions among psychological and social determinants of pain through examination of the process of pain communication. The focus is on an improved understanding of immediate dyadic transactions during painful events in the context of broader social phenomena. Fine-grain consideration of social transactions during pain leads to an appreciation of sociobehavioral events affecting both suffering persons as well as caregivers. Our examination considers knowledge from a variety of perspectives, including clinical health psychology, social and developmental processes, evolutionary psychology, communication studies, and behavioral neuroscience.

To what extent do we share the pain of others? Insight from the neural bases of pain empathy

In the representationalist framework generally adopted in cognitive neuroscience, pain is conceived as a subjective experience triggered by the activation of a mental representation of actual or potential tissue damage (nociception). This representation may involve somatic sensory features, as well as affective-motivational reactions associated with the promotion of protective or recuperative visceromotor and behavioral responses. Mental representation of nociception may provide the primary referent from which a rich associative network can be established to evoke the notion of pain in the absence of a nociceptive stimulus. Here, we adopt the notion of a mental representation of pain as a means to relate the experience of pain in oneself to the perception of pain in others. We review the functional neuroimaging studies supporting the hypothesis that the perception of pain in others relies at least partly on the activation of a mental representation of pain in the Self, and thus on common neural systems. However, we also demonstrate that there are

Pain-related emotions modulate experimental pain perception and autonomic responses

&NA; The effect of emotions on pain perception is generally recognized but the underlying mechanisms remain unclear. Here, emotions related to pain were induced in healthy volunteers using hypnosis, during 1‐min immersions of the hand in painfully hot water. In Experiment 1, hypnotic suggestions were designed to induce various positive or negative emotions. Compared to a control condition with hypnotic‐relaxation, negative emotions produced robust increases in pain. In Experiment 2, induction of pain‐related anger and sadness were found to increase pain. Pain increases were associated with increases in self‐rated desire for relief and decreases in expectation of relief, and with increases in arousal, negative affective valence and decreases in perceived control. In Experiment 3, hypnotic suggestions specifically designed to increase and decrease the desire for relief produced increases and decreases in pain, respectively. In all three experiments, emotion‐induced changes in pain were most consistently found on ratings of pain unpleasantness compared to pain intensity. Changes in pain‐evoked cardiac responses (R–R interval decrease), measured in experiments 2 and 3, were consistent with changes in pain unpleasantness. Correlation and multiple regression analyses suggest that negative emotions and desire for relief influence primarily pain affect and that pain‐evoked autonomic responses are strongly associated with pain affect. These results confirm the hypothesized influence of the desire for relief on pain perception, and particularly on pain affect, and support the functional relation between pain affect and autonomic nociceptive responses. This study provides further experimental confirmation that pain‐related emotions influence pain perception and pain‐related physiological responses.

Descending analgesia – When the spine echoes what the brain expects

Abstract Changes in pain produced by psychological factors (e.g., placebo analgesia) are thought to result from the activity of specific cortical regions. However, subcortical nuclei, including the periaqueductal gray and the rostroventral medulla, also show selective activation when subjects expect pain relief. These brainstem regions send inhibitory projections to the spine and produce diffuse analgesic responses. Regrettably the precise contribution of spinal mechanisms in predicting the strength of placebo analgesia is unknown. Here, we show that expectations regarding pain radically change the strength of spinal nociceptive responses in humans. We found that contrary to expectations of analgesia, expectations of hyperalgesia completely blocked the analgesic effects of descending inhibition on spinal nociceptive reflexes. Somatosensory‐evoked brain potentials and pain ratings further confirmed changes in spino‐thalamo‐cortical responses consistent with expectations and with changes in the spinal response. These findings provide direct evidence that the modulation of pain by expectations is mediated by endogenous pain modulatory systems affecting nociceptive signal processing at the earliest stage of the central nervous system. Expectation effects, therefore, depend as much about what takes place in the spine as they do about what takes place in the brain. Furthermore, complete suppression of the analgesic response normally produced by descending inhibition suggests that anti‐analgesic expectations can block the efficacy of pharmacologically valid treatments which has important implications for clinical practice.

Cortical Thickness and Pain Sensitivity in Zen Meditators

Zen meditation has been associated with low sensitivity on both the affective and the sensory dimensions of pain. Given reports of gray matter differences in meditators as well as between chronic pain patients and controls, the present study investigated whether differences in brain morphometry are associated with the low pain sensitivity observed in Zen practitioners. Structural MRI scans were performed and the temperature required to produce moderate pain was assessed in 17 meditators and 18 controls. Meditators had significantly lower pain sensitivity than controls. Assessed across all subjects, lower pain sensitivity was associated with thicker cortex in affective, pain-related brain regions including the anterior cingulate cortex, bilateral parahippocampal gyrus and anterior insula. Comparing groups, meditators were found to have thicker cortex in the dorsal anterior cingulate and bilaterally in secondary somatosensory cortex. More years of meditation experience was associated with thicker gray matter in the anterior cingulate, and hours of experience predicted more gray matter bilaterally in the lower leg area of the primary somatosensory cortex as well as the hand area in the right hemisphere. Results generally suggest that pain sensitivity is related to cortical thickness in pain-related brain regions and that the lower sensitivity observed in meditators may be the product of alterations to brain morphometry from long-term practice.