Ethnic differences in thermal pain responses.

OBJECTIVE: Although numerous studies have reported ethnic differences in the prevalence and severity of clinical pain, little is known about how these differences affect the perception of experimental pain. The present experiment examined the effects of ethnicity (African American vs. white) on thermal pain responses in a healthy undergraduate population. METHODS: Thirty white subjects (16 women and 14 men) and 18 African Americans (10 women and 8 men) participated in the study. Thermal testing included evaluation of the following: warmth thresholds, thermal pain thresholds, thermal pain tolerances, and magnitude estimates of both the intensity and unpleasantness of thermal pain (at 46 degrees, 47 degrees, 48 degrees, and 49 degrees C). RESULTS: Although no group differences emerged for warmth thresholds, thermal pain thresholds, or pain intensity ratings, African Americans demonstrated lower thermal pain tolerances than whites. In addition, African Americans had smaller slopes and larger intercepts than whites for ratings of pain unpleasantness. Additional analyses suggested that these findings were a consequence of group differences in thermal pain unpleasantness ratings at the lowest temperatures assessed (46 degrees and 47 degrees C); at these temperatures, African Americans rated the stimuli as more unpleasant than whites. Finally, group differences in thermal pain tolerance and thermal pain unpleasantness ratings seemed to partially account for greater self-reported daily pain symptoms among African Americans. CONCLUSIONS: Collectively, these findings seem to suggest ethnic differences in the perception of the affective-motivational dimension of thermal pain.     

Race and sex differences in cutaneous pain perception

OBJECTIVE: The purpose of this study was to determine race and sex differences in cutaneous pain perception. METHODS: Pain perception was measured using a suprathreshold evaluation of pain intensity and pain unpleasantness to a series of thermal stimuli in 27 whites (14 men and 13 women) and 24 African Americans (12 men and 12 women). Blood pressure, depressive symptoms, anxiety state levels, and negative mood were assessed before pain testing to examine whether they might account for any sex or race differences in pain perception that emerged. RESULTS: African Americans rated the stimuli as more unpleasant and showed a tendency to rate it as more intense than whites. Women showed a tendency to rate the stimuli as more unpleasant and more intense than men. In addition, systolic blood pressure was inversely related to pain intensity. After statistically adjusting for systolic blood pressure, sex differences in pain unpleasantness were reduced and sex differences in pain intensity were abolished; race differences were unaltered. CONCLUSIONS: These differences in pain perception may be associated with different pain mechanisms: in the ease of sex, differences in opioid activity and baroreceptor-regulated pain systems; in the case of race, unmeasured psychological characteristics are suggested by the larger differences in ratings of pain unpleasantness than pain intensity.     

Spatial summation of heat-induced pain: influence of stimulus area and spatial separation of stimuli on perceived pain sensation intensity and unpleasantness

1. Psychophysical experiments were initiated to determine the possible influence of increasing stimulus size on perceived pain intensity. Six trained human subjects (5 male, 1 female) made visual analogue scale (VAS) ratings for pain-sensation intensity and unpleasantness in response to nociceptive thermal stimuli. Test stimuli consisted of 5-s duration heat pulses (45-50 degrees C in 1 degrees increments) delivered by one, two, or three contact thermal probes (1 cm2 each) applied to the medial aspect of the anterior forearm. 2. The area of skin receiving noxious thermal stimuli was changed by randomly varying the number of thermodes activated. The effects of varying the distance between the thermal probes also were evaluated. In the first series of experiments, thermal-probe separation was kept close to 0; in subsequent experimental series, the thermodes were separated by either 5 or 10 cm. 3. In each experimental series, considerable spatial summation occurred in both pain-sensation intensity and unpleasantness dimensions of pain. This summation occurred throughout the nociceptive thermal range of 45-50 degrees C and was larger at suprathreshold temperatures (greater than or equal to 47 degrees C) than those near threshold (less than or equal to 46 degrees C). Unlike spatial summation of perceived warmth, that of pain was not characterized by systematic changes in power-function exponents but as approximately upward parallel displacements in double-logarithmic coordinates. 4. Thermal-probe separation over a range of 0-10 cm had no effects on spatial summation of pain-sensation intensity or pain unpleasantness. In contrast, increasing thermal-probe separation increased the subjects' ability to discriminate differences in stimulus size and their ability to detect correctly the number of thermal probes activated. 5. Because affective VAS ratings of unpleasantness were linearly related to, but distinctly and systematically less than, VAS ratings of pain-sensation intensity, it was clear that subjects responded quite differently to these two pain dimensions. Affective judgements were not additionally influenced by thermal probe separation and hence by the ability to perceive stimulus size or number of thermal probes activated. 6. The results indicate that powerful spatial-summation mechanisms exist for heat-induced pain. Spatial summation of pain is likely to be subserved both by local integration mechanisms at the level of single spinothalamic-tract neurons and by recruitment of central nociceptive neurons, because spatial summation of pain occurred to approximately equal extents under conditions of thermode separations over a distance of at least 20 cm.     

Blood pressure and the perception of illusive pain

Numerous studies have documented an inverse relationship between blood pressure and sensitivity to experimental nociceptive stimulation. The present study aimed to investigate possible associations between blood pressure and the occurrence and intensity of paradoxical pain induced by the thermal grill paradigm. Thirty‐one healthy subjects were stimulated three times for 1 min with the nonnoxious temperatures of 15°C and 41°C set at the interlaced cold and warm bars of a water bath‐driven thermal grill. Blood pressure and heart rate were recorded concomitantly. On account of previous observations of an association between the sensitivity of the cardiac baroreflex and pain perception, this parameter was additionally obtained. Numerical rating scales were used to quantify subjective pain intensity and pain unpleasantness; subjects were classified as responders and nonresponders to thermal grill stimulation based on pain intensity ratings. Responders exhibited lower systolic and diastolic blood pressure than nonresponders, and inverse linear associations arose between blood pressure and pain intensity and unpleasantness. Baroreflex sensitivity was unrelated to pain ratings. The findings confirmed the hypothesis of a blood pressure dependence of paradoxical pain and support the notion that the cardiovascular and pain regulatory systems interact not only in the processing of pain elicited by noxious input, but also in nonnoxiously generated illusive pain. While this finding is not consistent with the assumption of an involvement of the baroreflex system in mediating the observed interaction, psychological traits and neurochemical factors are alternatively considered.     

The relationship between resting blood pressure and acute pain sensitivity: effects of chronic pain and alpha-2 adrenergic blockade

This study tested for alpha-2 adrenergic mediation of the inverse relationship between resting blood pressure and acute pain sensitivity in healthy individuals. It also replicated limited prior work suggesting this inverse blood pressure/pain association is altered in chronic pain, and provided the first test of whether chronic pain-related changes in alpha-2 adrenergic function contribute to these alterations. Resting blood pressure was assessed in 32 healthy controls and 24 chronic low back pain participants prior to receiving placebo or an intravenous alpha-2 adrenergic receptor antagonist (yohimbine hydrochloride, 0.4 mg/kg) in a randomized crossover design. Participants experienced three acute pain tasks during both sessions. A significant Systolic Blood Pressure × Participant Type × Drug interaction on finger pressure McGill Pain Questionnaire-Sensory ratings (P < .05) reflected significant hyperalgesic effects of yohimbine in chronic pain participants with lower systolic blood pressures (P < .05) but not those with higher systolic pressures, and no significant effects of yohimbine in controls regardless of blood pressure level. A Drug × Systolic Blood Pressure interaction on finger pressure visual analog scale unpleasantness indicated the inverse blood pressure/pain association was significantly stronger under yohimbine relative to placebo (P < .05). Significant Participant Type × Systolic Blood Pressure interactions (P’s < .05) were noted for finger pressure visual analog scale pain intensity and unpleasantness, ischemic pain threshold, and heat pain threshold, reflecting absence or reversal of inverse blood pressure/pain associations in chronic pain participants. Results suggest that blood pressure-related hypoalgesia can occur even when alpha-2 adrenergic systems are blocked. The possibility of upregulated alpha-2 adrenergic inhibitory function in chronic pain patients with lower blood pressure warrants further evaluation.     

Heart rate variability and pain: associations of two interrelated homeostatic processes

Between-person variability in pain sensitivity remains poorly understood. Given a conceptualization of pain as a homeostatic emotion, we hypothesized inverse associations between measures of resting heart rate variability (HRV), an index of autonomic regulation of heart rate that has been linked to emotionality, and sensitivity to subsequently administered thermal pain. Resting electrocardiography was collected, and frequency-domain measures of HRV were derived through spectral analysis. Fifty-nine right-handed participants provided ratings of pain intensity and unpleasantness following exposure to 4 degrees C thermal pain stimulation, and indicated their thresholds for barely noticeable and moderate pain during three exposures to decreasing temperature. Greater low-frequency HRV was associated with lower ratings of 4 degrees C pain unpleasantness and higher thresholds for barely noticeable and moderate pain. High-frequency HRV was unrelated to measures of pain sensitivity. Findings suggest pain sensitivity is influenced by characteristics of a central homeostatic system also involved in emotion.     

Cortical processing of visceral and somatic stimulation: differentiating pain intensity from unpleasantness

Visceral and somatic pain perception differs in several aspects: poor localization of visceral pain and the ability of visceral pain to be referred to somatic structures. The perception of pain intensity and affect in visceral and somatic pain syndromes is often different, with visceral pain reported as more unpleasant. To determine whether these behavioral differences are due to differences in the central processing of visceral and somatic pain, non-invasive imaging tools are required to examine the neural correlates of visceral and somatic events when the behavior has been isolated and matched for either unpleasantness or pain intensity. In this study we matched the unpleasantness of somatic and visceral sensations and imaged the neural representation of this perception using functional magnetic resonance imaging in 10 healthy right-handed subjects. Each subject received noxious thermal stimuli to the left foot and midline lower back and balloon distension of the rectum while being scanned. Stimuli were matched to the same unpleasantness rating, producing mild-moderate pain intensity for somatic stimuli but an intensity below the pain threshold for the visceral stimuli. Visceral stimuli induced deactivation of the perigenual cingulate bilaterally with a relatively greater activation of the right anterior insula-i.e. regions encoding affect. Somatic pain induced left dorso-lateral pre-frontal cortex and bilateral inferior parietal cortex activation i.e. regions encoding spatial orientation and assessing perceptual valence of the stimulus. We believe that the observed patterns of activation represent the differences in cortical process of interoceptive (visceral) and exteroceptive (somatic) stimuli when matched for unpleasantness.     

Pain and emotion: effects of affective picture modulation

OBJECTIVE AND METHODS: Two experiments examined the impact of viewing unpleasant, pleasant, and neutral photographic slides on cold-pain perception in healthy men and women. In each experiment, participants viewed one of three slide shows (experiment 1 = fear, disgust, or neutral; experiment 2 = erotic, nurturant, or neutral) immediately before a cold-pressor task. Skin conductance and heart rate were recorded during the slide shows, whereas visual analog scale ratings of pain intensity and unpleasantness thresholds and pain tolerance were recorded during the cold-pressor task. RESULTS: Viewing fear and disgust slides decreased pain intensity and unpleasantness thresholds, but only the fear slides decreased pain tolerance. In contrast, viewing erotic, but not nurturant, slides increased pain intensity and unpleasantness threshold ratings on the visual analog scale in men, whereas neither nurturant nor erotic slides altered pain tolerance. CONCLUSIONS: These results are consistent with a motivational priming model that predicts that unpleasant affective states should enhance pain and that pleasant affective states should attenuate it.     

Reduced tolerance and cardiovascular response to ischemic pain in minor depression

BACKGROUND: A paradoxical association between a higher prevalence of clinical pain and a reduced sensitivity to brief experimental pain seems to exist during depression. METHODS: We assessed the responses to sustained ischemic pain produced by a maximal effort tourniquet procedure in 32 controls and 11 individuals with minor depression (Zung autoscale > or =50). Stethoscopic blood pressures and heart rates were monitored throughout the procedure. RESULTS: Measures of pain threshold, and measures of pain intensity and pain unpleasantness during the ischemic procedure were similar in depressed and control subjects. Yet, the overall numerical ratings of ischemic pain during the procedure was 28% higher and pain tolerance was 44% lower in depressed compared to control subjects. Clinical pain complaints were reported by 91% of depressed but only by 41% of control subjects (P = 0.01). Sustained ischemic pain induced significant elevations of systolic and mean arterial blood pressures in controls but not in depressed subjects. LIMITATIONS: The main limitation of the present study was the preponderance of females in the depressed group. Yet, we did not find significant gender differences in the sensory-affective and autonomic responses to ischemic pain in our sample. CONCLUSIONS: These findings suggest alterations in the sensory and autonomic nervous systems during minor depression.     

Will it hurt less if I believe I can control it? Influence of actual and perceived control on perceived pain intensity in healthy male individuals: a randomized controlled study

We explored the effects of uncontrollability and subjective helplessness (SHL) on perceived pain intensity (PPI) in 64 healthy men randomly assigned to groups receiving controllable (C) or uncontrollable (UC) painful electric skin stimuli. SHL (d = 1.43), perceived unpleasantness (d = 1.03), and PPI (d = 0.58) were more pronounced in the UC group than in the C group. Multiple regression and bootstrap analyses for testing mediation showed a direct relationship between stressor uncontrollability and PPI (r = 0.28; P < .05), which disappeared when adjusted for the SHL increase (β = 0.49, P < .001). SHL changes were associated with objective uncontrollability (r = 0.59, P < .001). PPI and unpleasantness were positively correlated (r = 0.37, P < .01). The study suggests that the effect of objective controllability on pain intensity ratings is mediated mainly by ratings of SHL.     

Blood pressure and pain sensitivity in children and adolescents

Elevated blood pressure is associated with diminished pain sensitivity. While this finding is well established in adults, it is less clear when the relation between blood pressure and pain sensitivity emerges across the life course. Evidence suggests this phenomenon may exist during childhood. Children (N = 309; 56% boys) aged 10–15 years and their parents participated. Blood pressure readings were taken during a resting baseline. Maximum pain intensity was rated using a visual analogue scale (rated 0–10) in response to a finger prick pain induction. Parent‐measured resting blood pressure was inversely associated with boys' pain ratings only. Cross‐sectionally, lower pain ratings were related to higher SBP, univariately. Longitudinally, pain ratings predicted higher DBP, even after controlling for covariates. Determining when and how the relation between blood pressure and pain sensitivity emerges may elucidate the pathophysiology of hypertension.     

Attenuation of sensory and affective responses to heat pain: evidence for contralateral mechanisms

Attenuation of responses to repeated sensory events has been thoroughly studied in many modalities; however, attenuation of pain perception has not yet benefitted from such extensive investigation. Described here are two psychophysical studies that examined the effects of repeated exposure to thermal stimuli, assessing potential attenuation of the perception of pain and its possible spatial specificity. Twenty-two subjects were presented thermal stimuli to the volar surface of the right and left forearms. Twelve subjects in study 1 received the same stimuli and conditions on each of five daily experimental sessions, whereas 10 subjects in study 2 received thermal stimuli, which were restricted to one side for four daily sessions and then applied to the other side on the fifth session. Ratings of warmth intensity, pain intensity, and pain unpleasantness were recorded while the subjects performed a thermal sensory discrimination task. Results of study 1 demonstrate that repeated stimulation with noxious heat can lead to long-term attenuation of pain perception; results of study 2 extend these findings of attenuation to both pain intensity and unpleasantness and show that this effect is highly specific to the exposed body side for both aspects of the pain experience. We suggest that the functional plasticity underlying this attenuation effect lies in brain areas with a strong contralateral pattern of pain-related activation.     

Influence of pain anticipation on brain activity and pain perception in Gulf War Veterans with chronic musculoskeletal pain

Anticipation of a painful experience can influence brain activity and increase sensitivity to experimental somatosensory stimuli in healthy adults, but this response is poorly understood among individuals with chronic musculoskeletal pain (CMP). Studies of brain and perceptual responses to somatosensory stimuli are used to make inferences about central nervous system dysfunction as a potential mechanism of symptoms. As such, we sought to (a) determine the influence of pain anticipation on pain‐relevant brain regions and pain perception, and (b) characterize potential differences in these responses between Gulf War Veterans with CMP and matched healthy control (CO) Veterans. CMP (N = 30) and CO Veterans (N = 31) were randomized to conditions designed to generate expectations that either painful (pain) or nonpainful (no pain) stimuli would be administered. Brain responses to five nonpainful thermal stimuli were measured during fMRI, and each stimulus was rated for pain intensity and unpleasantness. In the pain condition, an incremental linear decrease in activity across stimuli was observed in the posterior cingulate cortex, cingulate cortex, and middle temporal gyrus. Further, in the pain condition, differential responses were observed between CMP and CO Veterans in the middle temporal gyrus. These findings indicate that brain responses to nonpainful thermal stimuli in Veterans with CMP are sensitive to pain anticipation, and we recommend accounting for the influence of pain anticipation in future investigations of central nervous system dysfunction in CMP.     

Musically induced arousal affects pain perception in females but not in males: a psychophysiological examination

The present study investigated affective and physiological responses to changes of tempo and mode in classical music and their effects on heat pain perception. Thirty-eight healthy non-musicians (17 female) listened to sequences of 24 music stimuli which were variations of 4 pieces of classical music. Tempo (46, 60, and 95 beats/min) and mode (major and minor) were manipulated digitally, all other musical elements were held constant. Participants rated valence, arousal, happiness and sadness of the musical stimuli as well as the intensity and the unpleasantness of heat pain stimuli which were applied during music listening. Heart rate, respiratory rate and end-tidal PCO(2) were recorded. Pain ratings were highest for the fastest tempo. Also, participants' arousal ratings, their respiratory rate and heart rate were accelerated by the fastest tempo. The modulation of pain perception by the tempo of music seems to be mediated by the listener's arousal.     

High-frequency rTMS of the motor cortex does not influence the nociceptive flexion reflex but increases the unpleasantness of electrically induced pain

The aim of this study was to investigate whether a 10-Hz repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex, using a stimulus paradigm employed for pain control in chronic pain, affects acute electrically induced pain. We investigated whether rTMS modulates the nociceptive flexion reflex (NFR) in addition to subjective pain perception. Pain threshold, NFR threshold, supra-threshold NFR response, and the concomitant pain intensity and pain unpleasantness visual analogue scale (VAS) scores were compared before and after 20 min of rTMS. Effects of 20 trains of 5 s' duration (55 s intertrain interval) of 10-Hz rTMS at 80% of the resting motor threshold (RMT) applied over the dominant motor cortex were compared to sham rTMS in 12 healthy volunteers. Supra-threshold NFR stimulation significantly increased pain unpleasantness VAS scores with real rTMS compared to sham rTMS (F(1,10)=6.91; P=0.025). There was no significant effect of 10-Hz rTMS on the subjective pain threshold or on the NFR, neither at threshold nor at supra-threshold noxious stimulation. The rTMS paradigm used to control chronic pain is not suitable for controlling Adelta fiber-mediated acute experimentally induced pain since the effects on pain perception were only marginal, with an increase in the VAS unpleasantness scores but with no effect on the NFR. The increased activity of cortico-thalamic projections might modulate the perception of Adelta fiber-mediated pain within the lateral pain pathway. The type of fiber that is stimulated and neuroplastic changes in chronic pain and are thought to be critical for rTMS to have an effect.     

Brief submaximal isometric exercise improves cold pressor pain tolerance

Exercise-induced hypoalgesia (EIH), or the inhibition of pain following physical exercise, has been demonstrated in adults, but its mechanisms have remained unclear due to variations in methodology. This study aimed to address methodological imitations of past studies and contribute to the literature demonstrating the generalizability of EIH to brief submaximal isometric exercise and cold pressor pain. Young adults (n = 134) completed a baseline cold pressor trial, maximal voluntary contraction (hand grip strength) assessment, 10-min rest, and either a 2-min submaximal isometric handgrip exercise or a sham exercise in which no force was exerted, followed by a cold pressor posttest. Results indicated that cold pressor pain tolerance significantly increased during the exercise condition, but not during the sham exercise condition. Exercise did not affect pain intensity and marginally affected pain unpleasantness ratings. These findings suggest that submaximal isometric exercise can improve cold pressor pain tolerance but may have an inconsistent analgesic effect on ratings of cold pressor pain.     

Why look in the brain for answers to temporomandibular disorder pain?

Temporomandibular disorder (TMD) patients often exhibit widespread clinical pain, as well as greater sensitivity to experimental pain than pain-free controls, suggesting a role of central pathophysiologic mechanisms in TMD. Moreover, TMD is more prevalent among women, which may be related to the higher sensitivity of women to experimental pain. Women also exhibit greater temporal summation of heat pain compared to men. Temporal summation, the increase in pain intensity upon repetitive noxious stimulation of constant intensity, at a high frequency is centrally mediated. Thus, greater temporal summation in women indicates that their central nociceptive processing is upregulated compared to men. Recent studies in our research center sought further evidence for upregulation of central nociceptive processing in females compared to males and in TMD patients compared to healthy controls, assessing group differences in temporal summation of mechanically evoked pain, and aftersensations following repetitive noxious stimulation. Sixteen series of 10 repetitive, sharp, mechanical stimuli were applied to the fingers of 25 female TMD patients, 25 healthy women, and 25 healthy men, with a computer-controlled small probe. All subjects rated the pain intensity or the unpleasantness evoked by the 1st, 5th and 10th stimulus in the series, and the aftersensations 15 s and 1 min after the last stimulus on visual-analog scales. TMD patients exhibited greater temporal summation of pain and unpleasantness, stronger aftersensations, and more frequent painful aftersensations than controls. Healthy females showed greater temporal summation of pain intensity and unpleasantness, higher intensity and unpleasantness of aftersensations, and more frequent painful aftersensations than males. Greater temporal summation of pain and aftersensations from digital stimulation of TMD patients than controls suggest a generalized hyperexcitability of the central nociceptive system in this patient group. Such hyperexcitability may contribute to the development and/or maintenance of chronic TMD pain. Moreover, greater temporal summation of pain and aftersensations in healthy females than males indicate that their central processing of nociceptive input may be more easily upregulated into pathological hyperexcitability, possibly accounting for the predominance of TMD among women.     

Effects of PRES baroreceptor stimulation on thermal and mechanical pain threshold in borderline hypertensives and normotensives

Prior studies have noted a pain relieving effect of baroreceptor stimulation and of higher tonic blood pressure in animals and humans. The present study used a new technique for the controlled, noninvasive stimulation of human carotid baroreceptors (PRES). PRES baroreceptor manipulation was delivered to both normotensive subjects (n= 11) and medication-free labile hypertensive subjects (n= 10) during both thermal and mechanical pain. Consistent with prior research, hypertensives had a higher threshold for thermal pain than did normotensives. PRES baroreceptor manipulation had no significant effect on thermal pain threshold for either group. For the mechanical pain model, the opposite results were obtained; group pain threshold did not differ, but there was a significant PRES baroreceptor stimulation effect of increasing pain threshold for both groups. Results are discussed in terms of specific features of the stimuli, dampening of pain in hypertensives, and adaptation to pain.     

Thermal sensory decision theory indices and pain threshold in chronic pain patients and healthy volunteers

Fifty-five low back pain patients and 47 healthy volunteers judged the intensity of calibrated thermal stimuli. The method of constant stimuli yielded a pain threshold, and sensory decision theory (SDT) methods provided two independent indices of perceptual performance: discriminability, P(A), the ability to differentiate among various stimulus intensities; and report criterion, B, the tendency to use a particular response. Compared to healthy volunteers, chronic pain patients were far poorer discriminators [lower P(A)]. In addition, the chronic pain patients were more stoical (higher B) and had higher thresholds for reporting both very faint pain and pain. The poor discriminability in patients could be due to attenuation of afferent neural input. The higher criterion suggests that the thermal stimuli were perceived as being innocuous relative to their clinical pain. Comparison of SDT indices with the threshold measures revealed that the pain threshold was highly correlated to the subject's criterion for reporting pain, B, and unrelated to discriminability, P(A).     

Cortical representation of the sensory dimension of pain.

It is well accepted that pain is a multidimensional experience, but little is known of how the brain represents these dimensions. We used positron emission tomography (PET) to indirectly measure pain-evoked cerebral activity before and after hypnotic suggestions were given to modulate the perceived intensity of a painful stimulus. These techniques were similar to those of a previous study in which we gave suggestions to modulate the perceived unpleasantness of a noxious stimulus. Ten volunteers were scanned while tonic warm and noxious heat stimuli were presented to the hand during four experimental conditions: alert control, hypnosis control, hypnotic suggestions for increased-pain intensity and hypnotic suggestions for decreased-pain intensity. As shown in previous brain imaging studies, noxious thermal stimuli presented during the alert and hypnosis-control conditions reliably activated contralateral structures, including primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate cortex, and insular cortex. Hypnotic modulation of the intensity of the pain sensation led to significant changes in pain-evoked activity within S1 in contrast to our previous study in which specific modulation of pain unpleasantness (affect), independent of pain intensity, produced specific changes within the ACC. This double dissociation of cortical modulation indicates a relative specialization of the sensory and the classical limbic cortical areas in the processing of the sensory and affective dimensions of pain.