M. Catherine Bushnell

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.

Effects of attention on the intensity and unpleasantness of thermal pain.

&NA; Both experimental and clinical studies have shown that psychological manipulations, such as hypnosis, behavioral modification and cognitive‐behavioral therapy, can reduce reports of pain. Although these are complex procedures, one important variable common to each is direction of attention. We have previously demonstrated in both humans and monkeys a method for monitoring and manipulating attention toward or away from a painful stimulus and have shown that changes in the direction of attention alter the ability to discriminate noxious heat stimuli. The present study assessed whether these changes in discrimination were accompanied by changes in the perception of pain intensity and/or unpleasantness. These data confirm that both the speed and accuracy of detecting changes in noxious heat stimuli are decreased when the subject attends to another stimulus modality. In addition, they show that direction of attention affects the perceived intensity and unpleasantness of painful stimuli in a similar manner. Our previous findings of attention‐related modulation of nociceptive neuronal activity in the medullary dorsal horn suggest that these attention‐dependent changes in sensory‐discriminative and affective components of pain are mediated at early stages of sensory processing.

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.

Sex differences in the perception of noxious heat stimuli

&NA; This study compared pain perception in young male and female subjects, using experimental noxious heat stimuli. During 2 sessions, each of 40 subjects rated the magnitude of 120 heat stimuli, ranging from 45°C to 50°C. The study included a comparison of visual analogue and magnitude matching rating procedures, as well as a test of simulated analgesia, in which the range of stimuli presented during the 2 experimental sessions was shifted by 1°C. We found that females rated noxious heat stimuli as more intense than did males, independent of the gender of the experimenter or the type of rating scale. In addition, the data suggest that females discriminate among the painful heat intensities better than males. For example, female subjects showed significant between‐session discrimination of noxious heat stimuli, while male subjects did not, and females produced steeper within‐session stimulus‐response functions than did males. These observed differences in nociceptive discrimination between males and females indicate that the sex‐related variation in pain perception is probably related to sensory factors rather than differences in attitude or emotional response.

Comparison of verbal and visual analogue scales for measuring the intensity and unpleasantness of experimental pain

&NA; Although the multidimensional nature of pain is now well recognized, there are, nevertheless, very few quantitative tests to measure the separate dimensions of pain and little data concerning their relative sensitivity. The present study compares 2 currently available methods, verbal descriptor and visual analogue scales. Eight subjects rated painful and near‐painful heat stimuli by using visual analogue scales for intensity or unpleasantness and by choosing the most appropriate phrases from lists of intensity or unpleasantness descriptors. In the intensity dimension, the relationship between perception and stimulus temperature was essentially identical whether calculated from the visual analogue or verbal descriptor scales. However, data derived from the verbal descriptor scales revealed that subjects rated the painful temperatures as relatively more intense than unpleasant; this difference could not be detected using the visual analogue scales. These results confirm that both visual analogue and verbal descriptor techniques successfully quantify sensory intensity and affective aspects of pain, but that verbal descriptors may provide the more sensitive tool for separating intensity and unpleasantness.

Deep brain stimulation: a review of basic research and clinical studies

&NA; Deep brain stimulation for pain control in humans was first used almost 30 years ago and has continued to receive considerable attention. Despite the large number of clinical reports describing pain relief, numerous studies have indicated that the results of these procedures vary considerably. In addition, many neurosurgeons find the procedures unpredictable, and considerable disagreement still exists regarding important issues related to the technique itself. This review gives an historical overview of the relevant basic and clinical literature and provides a critical examination of the clinical efficacy, choice of stimulation sites, parameters of stimulation, and effects on experimental pain. Finally, we give suggestions for future research that could more definitively determine the usefulness of deep brain stimulation for pain control.

Noxious and innocuous cold discrimination in humans: evidence for separate afferent channels

&NA; The present study evaluated the ability of humans to discriminate temperature decreases in the noxious and innocuous cold range. Two groups of five subjects detected changes in cold stimuli applied to the maxillary face. For five subjects, adapting temperatures of 22°, 16°, and 0°C were used, and thresholds for detecting temperature decreases were determined using an adaptive psychophysical paradigm. Visual analogue scale (VAS) ratings of cold and pain sensation were also recorded at 5‐min intervals throughout each session. A second group of five subjects performed a similar detection task, but in this case using classical psychophysical techniques (method of constant stimuli) and adapting temperatures of 22°, 16°, 10° and 6°C. These subjects described the quality of the detected change in sensation, in addition to rating overall cold and pain sensation throughout the session. Detection thresholds were 0.27°, 0.48°, 4.8°, 8.0° and > 10.0°C for baselines of 22°, 16°, 10°, 6° and 0°C, respectively, indicating that discrimination was better in the innocuous cool (22° and 16°C) than in the noxious and near‐noxious cold (10‐0°C) range (P < 0.05). Tonic adapting temperatures of 22° and 16°C were always rated as cool but not painful, whereas adapting temperatures of 10° and 6° were sometimes and 0°C usually rated as painful. Phasic temperature decreases from 22° and 16°C always produced cooling sensations, whereas decreases from baselines of 10° and 6°C produced primarily sensations of painful and non‐painful prickle. These data suggest that different afferent channels mediate cool and noxious cold perception and add support to the hypothesis that noxious cold sensation is mediated by subdermal nociceptors.

Preoperative Flurbiprofen in Oral Surgery: A Method of Choice in Controlling Postoperative Pain

The analgesic efficacy of a single 50‐mg preoperative dose of flurbiprofen was compared with ACC‐30 (aspirin 375 mg, codeine 30 mg, caffeine 30 mg) and a placebo. Forty patients scheduled for the surgical removal of impacted maxillary third molars were enrolled in a double‐blind, randomized study. Using a within‐subject design we compared the analgesic efficacy of (1) preoperative flurbiprofen 50 mg with placebo in 20 patients, and (2) preoperative ACC‐30 with placebo in 20 other patients. Using a between‐group design, we then compared the analgesic efficacy of (3) each drug given preoperatively and postoperatively, and (4) each drug given postoperatively only. Patients rated 2 pain dimensions, intensity and unpleasantness, hourly for 8 hours after the presurgical dose. The results of this study indicate that better analgesia was obtained when flurbiprofen was given preoperatively compared to only after surgery. Conversely, preoperative administration of ACC‐30 did not demonstrate any significant influence on postsurgical analgesia. When comparing the 2 drugs, flurbiprofen proved to be superior in providing pain relief only when it was given prior to surgery. There was no difference between them when given only after surgery. Side effects were moderate and not significantly different between patients receiving flurbiprofen and those receiving ACC‐30.

A model of transient hyperalgesia in the behaving monkey induced by topical application of capsaicin

Abstract The aim of this study was to develop a model of transient hyperalgesia in the awake monkey performing operant tasks. An adult male rhesus monkey was trained to press a lever to receive food reward for detecting a light or to escape mechanical or thermal stimuli applied in the maxillary region of the face. A small contact thermode was positioned on one side of the face and a mechanical stimulator was placed on the other side. Noxious and innocuous thermal (43, 47 and 51°C) or mechanical (245, 490, 736 and 1472 mN) stimuli of 4.5‐s duration were presented in a pseudo‐random order. The animal was tested before, 1 h and 24 h after topical capsaicin application (0.3 ml; 0.004 M). At the site of capsaicin application, the monkey escaped more thermal and mechanical stimuli 1 h after than before capsaicin, suggestive of thermal and mechanical hyperalgesia. At 24 h post‐capsaicin, mechanical escape behavior had returned to baseline, but thermal escapes were still slightly elevated. Capsaicin had no significant effect on either mechanical or thermal escape behavior for stimuli presented to the contralateral site. Seven human subjects tested with these procedures reported higher pain intensity for similar stimuli after capsaicin application, in accordance with the monkey escape behavior. It is concluded that topical application of capsaicin on the maxillary face of the awake behaving monkey produces a transient thermal and mechanical hyperalgesia. The procedure is repeatable and produces no overt signs of distress. Thus it could provide an important tool for studying neural mechanisms of hyperalgesia and for testing analgesic treatments in primates.