Remembering the dynamic changes in pain intensity and unpleasantness: a psychophysical study.

This study investigated the short-term memory of dynamic changes in acute pain using psychophysical methods. Pain intensity or unpleasantness induced by painful contact-heat stimuli of 8, 9, or 10s was rated continuously during the stimulus or after a 14-s delay using an electronic visual analog scale in 10 healthy volunteers. Because the continuous visual analog scale time courses contained large amounts of redundant information, a principal component analysis was applied to characterize the main features inherent to both the concurrent rating and retrospective evaluations. Three components explained about 90% of the total variance across all trials and subjects, with the first component reflecting the global perceptual profile, and the second and third components explaining finer perceptual aspects (eg, changes in slope at onset and offset and shifts in peak latency). We postulate that these 3 principal components may provide some information about the structure of the mental representations of what one perceives, stores, and remembers during the course of few seconds. Analysis performed on the components confirmed significant memory distortions and revealed that the discriminative information about pain dimensions in concurrent ratings was partly or completely lost in retrospective ratings. Importantly, our results highlight individual differences affecting these memory processes. These results provide further evidence of the important transformations underlying the processing of pain in explicit memory and raise fundamental questions about the conversion of dynamic nociceptive signals into a mental representation of pain in perception and memory.

Cortical thickness, mental absorption and meditative practice: possible implications for disorders of attention.

Mental training techniques rooted in meditation are associated with attention improvement, increased activation and cortical thickening of attention/executive-related brain areas. Interestingly, attention-deficit/hyperactivity disorder (ADHD) is associated with behavioural deficits, hypo-activation and cortical thinning of similar networks. This study assessed the relationship between prior meditative training, attentional absorption, and cortical thickness. Grey matter thickness was measured in 18 meditators and 18 controls. Subjective reports of attentional absorption were modestly higher in meditators and across the entire sample correlated positively with cortical thickness in several regions corresponding to cingulo-fronto-parietal attention networks. Within these regions the meditation group had greater cortical thickness which was positively related to the extent of prior training. Evidence suggesting that meditative practice activates these cortical areas, improves attention and may ameliorate symptoms of ADHD by targeting vulnerable brain regions is discussed.

Response competition in the primary motor cortex: corticospinal excitability reflects response replacement during simple decisions.

It has been suggested that, during decisions about actions, multiple options are initially specified in parallel and then gradually eliminated in a competition for overt execution. To further test this hypothesis, we studied the modulation of human corticospinal excitability during the reaction time of the Eriksen flanker task. In the task, subjects responded with finger flexion or extension to a central arrow while ignoring congruent or incongruent flanker arrows. Single-pulse transcranial magnetic stimulation (TMS) was applied over primary motor cortex (M1) at one of five different latencies after stimulus onset, and motor-evoked potentials (MEPs) were measured in the contralateral index finger. During the control (no flankers) and congruent conditions, MEP size in the agonist increased gradually over the course of reaction time, indicating an increase in corticospinal excitability. Conversely, when the same muscle acted as an antagonist, MEP size decreased, suggesting inhibition. Critically, in the incongruent condition, MEPs briefly increased in the muscle corresponding to an initial default response to the flanker arrows and were later replaced by MEPs corresponding to the correct response to the central arrow. Finally, we found that the gradually growing MEPs for the three conditions reached a constant maximum level just before movement initiation. We propose that this dynamic modulation in corticospinal excitability reflects the competition process, leading to the selection of one response and the rejection of the other. Our results suggest that response competition influences activity in primary motor cortex and that its timing directly influences motor output latency.

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.

Effects of cardiopulmonary baroreceptor activation on pain may be moderated by risk for hypertension.

Cardiopulmonary baroreceptor stimulation may modulate pain, though the literature is much smaller than research showing that sinoaortic baroreceptor stimulation can buffer pain. To examine the possibility that risk for established high blood pressure may moderate the effects of cardiopulmonary baroreceptor stimulation on pain, 22 borderline hypertensive and 18 normotensive men participated in a laboratory experiment. Group differences in blood pressure were documented by 24-h ambulatory blood pressure recording. Ratings of the intensity of acute heat pain were influenced by both group membership and leg position. Passive elevation of the legs, a technique that stimulates cardiopulmonary baroreceptors, reduced ratings of heat pain though only among borderline hypertensives. Alteration of pain sensitivity may reflect the development of the hypertensive process.

The anatomy of the mesolimbic reward system: a link between personality and the placebo analgesic response.

The anticipation of clinical benefit, a crucial component of placebo analgesia, has been suggested to be a special case of reward anticipation. Since reward processing is closely linked to the ventral striatum and the neurotransmitter dopamine, we examined the relationships between brain gray matter, placebo analgesic response, and personality traits associated with dopaminergic neurotransmission. We report that dopamine-related traits predict a substantial portion of the pain relief an individual gains from a sham treatment. Voxel-based morphometry of magnetic resonance images shows that the magnitude of placebo analgesia is related to gray matter density (GMD) in several brain regions, including the ventral striatum, insula, and prefrontal cortex. Similarly, GMD in ventral striatum and prefrontal cortex is related to dopamine-related personality traits. Our findings highlight the relationship between placebo and reward and potentially offer ways of identifying subjects who are likely to show large placebo analgesic responses.

Memory traces of pain in human cortex.

Distinct brain regions process sensory discriminative and affective components of pain; however, the role of these areas in pain memory is unknown. This event-related study investigated the short-term memory for sensory features of cutaneous heat pain using a delayed-discrimination paradigm and functional magnetic resonance imaging. During memory trials, subjects discriminated the location and intensity of two painful stimuli presented sequentially to the right hand. Control trials comprised the same sequence of stimuli and motor responses but required no delayed discrimination. Stimulus-evoked activity for memory and control trials was generally indistinguishable within the network of regions normally responsive to experimental pain [i.e., the primary somatosensory cortex/posterior parietal cortex (SI/PPC), secondary somatosensory cortex (SII), and anterior insular cortex (aIC)]; these data confirm the painful nature of the stimuli and the similar levels of attention and stimulus encoding engaged during the two randomly presented trial types. Memory-specific activity, assessed by contrasting the interstimulus interval in memory and control trials, was observed in SI/PPC and aIC but not in SII. We propose that SI/PPC plays a role in the short-term retention of spatial and intensity aspects of noxious stimuli and that aIC activation during memory trials is consistent with the integration of sensory and cognitive (attention, awareness, salience, and memory) components of pain perception. The absence of memory-specific anterior cingulate cortex activation, generally associated with pain unpleasantness, suggests that remembering affective aspects of the stimuli was not required during performance of the sensory delayed-discrimination task.

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.

Visceral and cutaneous pain representation in parasylvian cortex.

The ability to localize both touch and pain has been attributed mainly to the primary somatosensory cortex (S1), based on its fine somatotopic mapping of tactile inputs. Recently, S1 has also been implicated in the differentiation of noxious stimulation, such as distinguishing between pain arising from viscera and skin. Recent MEG and fMRI studies show that there is at least a rudimentary tactile topographic representation in the supra-sylvian cortex [encompassing secondary somatosensory area (S2)], suggesting that this area may contribute to touch localization. Nevertheless, the role of this region in pain localization or its role in the differentiation of various types of pain has not been clearly established. Healthy subjects (four males, three females) underwent fMRI-scanning (1.5 T, standard head coil, BOLD analysis) during painful balloon distention of the distal esophagus and painful heat on the midline chest in the zone of referred pain for the esophageal stimulation. Five of the seven subjects exhibited significant activation of the parasylvian region in both experimental conditions, and in each of these five subjects activation related to esophageal pain was represented more laterally within the parasylvian cortex than that associated with cutaneous trunk pain (paired t-test, p's < 0.01). Our results suggest segregation of visceral esophageal and cutaneous chest afferents within parasylvian cortex, possibly implicating this region in the perceptual differentiation of visceral and cutaneous pain.

The effects of racemic ketamine on painful stimulation of skin and viscera in human subjects.

Evidence suggests that NMDA receptors may have a differential role in the modulation of visceral and somatic pain. Specifically, animal data indicate an analgesic role of NMDA-R antagonists in acute visceral but not acute somatic pain. In humans analgesic effects are documented in acute somatic pain, while the role of NMDA-R antagonists in acute visceral pain is still questionable. We, therefore, conducted a study in humans comparing the analgesic effects of ketamine in an experimental model of visceral and cutaneous pain. In a double-blind, randomized, cross-over study, 11 healthy volunteers (3M, 8F) participated in two experimental sessions in which they evaluated perceptions induced by balloon distention of the distal esophagus and contact heat on the upper chest during continuous computer-controlled i.v. infusion of either ketamine (60 and 120 ng/mL) or saline. Two stimulus intensities producing non-painful and painful sensation were used for each stimulus modality. Subjects reported maximum pain intensity and unpleasantness on visual analog scales (VAS). For noxious visceral stimulation, low dose ketamine produced significant attenuation of both pain intensity and unpleasantness. In contrast, for noxious cutaneous stimulation, ketamine reduced pain unpleasantness, but not perceived intensity. In addition, ketamine did not alter the perception of innocuous stimuli in either modality. Our results confirm the analgesic effects of low-dose ketamine, with minimal side effects, on acute visceral pain and indicate a similar but smaller effect on acute cutaneous pain. A decrease in the unpleasantness but not in the intensity of cutaneous pain may reflect the differential effect of NMDA-R antagonists for the two pain states observed in animal models.

Rapid deterioration of pain sensory-discriminative information in short-term memory.

The assessment of pain and analgesic efficacy sometimes relies on the retrospective evaluation of pain felt in the immediate, recent or distant past, yet we have a very limited understanding of the processes involved in the encoding, maintenance and intentional retrieval of pain. We examine the properties of the short-term memory of thermal and pain sensation intensity with a delayed-discrimination task using pairs of heat pain, warm and cool stimulation in healthy volunteers. Performance decreased as a function of the inter-stimulus interval (ISI), indicating a robust deterioration of sensory information over the test period of 4-14 s. As expected, performance also decreased with smaller temperature differences (Delta-T) and shorter stimulus durations (6-2 s). The relation between performance and Delta-T was adequately described by a power function, the exponent of which increased linearly with longer ISI. Importantly, performance declined steadily with increasing ISI (from 6 to 14 s)--but only for pairs of heat pain stimuli that were relatively difficult to discriminate (Delta-T < or = 1.0 degree C; perceptual difference < or = 32/100 pain rating units) while no deterioration in performance was observed for the largest temperature difference tested (Delta T = 1.5 degrees C; perceptual difference of 50 units). These results are consistent with the possibility that short-term memory for pain and temperature sensation intensity relies on a transient analog representation that is quickly degraded and transformed into a more resistant but less precise categorical format. This implies that retrospective pain ratings obtained even after very short delays may be rather inaccurate but relatively reliable.

Analgesic and placebo effects of thalamic stimulation.

Numerous clinical studies have reported successful relief of chronic pain with sensory thalamic stimulation. However, even with the extensive use of sensory thalamic stimulation as a clinical tool in the relief of chronic pain, the results are still inconsistent. This discrepancy could probably be explained by the fact that the majority of these studies are case reports or retrospective analyses, which have often used imprecise pain measurements that do not allow a rigorous statistical evaluation of pain relief. None of these studies measured the effect of stimulation on clinical pain for longer than a few hours per day, which is an important aspect considering that clinical pain can vary over time. Moreover, placebo controls are seldom included. In the current study, we measured patients' pain perception at home over a 2-week period, both during days of normal stimulation of the sensory thalamus and during days without stimulation. Patients also came to the laboratory to assess the effects of thalamic and placebo stimulation on clinical pain, experimental heat pain, innocuous air puff and visual stimulation. A potential relation between the perceived paresthesia and analgesic efficacy during thalamic and placebo stimulation was also explored. We found that thalamic stimulation significantly affected clinical and experimental pain perception, but that an important placebo component also exists. On the other hand, neither thalamic nor placebo stimulation affected air puff and visual ratings, suggesting that the effect applies specifically to pain and hence is not caused by a general change in attention. The level of paresthesia elicited during the placebo manipulation was also directly correlated with the degree of placebo pain relief. These results suggest that thalamic stimulation produces a small but significant reduction in pain perception, but that a significant placebo effect also exists.

Is there a role for the parietal lobes in the perception of pain?

Converging lines of evidence confirm a role for the anterior parietal cortex in pain processing and extend the traditional view of SI to include discriminative aspects of somatic stimulation that is potentially tissue-damaging (e.g., painful). Recent studies more specifically implicate SI in the sensory aspect of pain perception by demonstrating that SI activation is modulated by cognitive manipulations that alter perceived pain intensity, but not by manipulations that alter unpleasantness, independent of pain intensity. Nevertheless, despite the probable role of SI in the encoding of the various sensory features of pain, considerable evidence suggests that nociceptive input to SI may also serve to modulate tactile perception. Thus, SI cortex may be involved in both the perception and modulation of both painful and nonpainful somatosensory sensations. Defining a role in pain processing for the parietal operculum is somewhat more problematic. The absence of a fine somatotopic organization of cutaneous (or visceral) receptors virtually eliminates a substantial role for this region in localizing noxious stimuli. Several studies suggest separate representations for pain and touch within the posterior parietal cortex and SII, respectively; however, inter-species differences in cortical anatomy and inconsistencies in the designation of SII proper preclude a clear reconciliation of the data. Likewise, suggestions that SII activation is predominantly related to processing the nociceptive quality of the stimulus (60,61) are inconsistent with many studies in both human and nonhuman subjects, which show a strong functional relationship between SII activity and innocuous (especially, vibrotactile) stimulation. Nevertheless, the numerous studies indicating pain-related activation within the parietal operculum (and/or SII) underscore the potential importance of this region in the perception of pain and the need for continued research. Finally, a possible role of posterior parietal cortex (BA 5/7, 39/40) in orientation and attention toward painful sensory stimuli is consistent with existing literature describing this region as a poly modal association area concerned with intrapersonal and extrapersonal space; however, results from studies that actually manipulate the subjects' level of attention relative to painful stimuli have not uniformly supported this hypothesis (75). Future studies assessing both attentional demand and direct manipulation or motor interactions involving noxious stimuli may help to resolve this issue. In spite of some discrepant results concerning specific details of the nociceptive process, the weight of human pain research now firmly establishes a role for the parietal lobes in the conscious appreciation of the sensation of pain.

Differentiation of visceral and cutaneous pain in the human brain.

The widespread convergence of information from visceral, cutaneous, and muscle tissues onto CNS neurons invites the question of how to identify pain as being from the viscera. Despite referral of visceral pain to cutaneous areas, individuals regularly distinguish cutaneous and visceral pain and commonly have contrasting behavioral reactions to each. Our study addresses this dilemma by directly comparing human neural processing of intensity-equated visceral and cutaneous pain. Seven subjects underwent fMRI scanning during visceral and cutaneous pain produced by balloon distention of the distal esophagus and contact heat on the midline chest. Stimulus intensities producing nonpainful and painful sensations, interleaved with rest periods, were presented in each functional run. Analyses compared painful to nonpainful conditions. A similar neural network, including secondary somatosensory and parietal cortices, thalamus, basal ganglia, and cerebellum, was activated by visceral and cutaneous painful stimuli. However, cutaneous pain evoked higher activation bilaterally in the anterior insular cortex. Further, cutaneous but not esophageal pain activated ventrolateral prefrontal cortex, despite higher affective scores for visceral pain. Visceral but not cutaneous pain activated bilateral inferior primary somatosensory cortex, bilateral primary motor cortex, and a more anterior locus within anterior cingulate cortex. Our results reveal a common cortical network subserving cutaneous and visceral pain that could underlie similarities in the pain experience. However, we also observed differential activation patterns within insular, primary somatosensory, motor, and prefrontal cortices that may account for the ability to distinguish visceral and cutaneous pain as well as the differential emotional, autonomic and motor responses associated with these different sensations.

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 brain's 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.

Differentiating noxious- and innocuous-related activation of human somatosensory cortices using temporal analysis of fMRI.

The role of the somatosensory cortices (SI and SII) in pain perception has long been in dispute. Human imaging studies demonstrate activation of SI and SII associated with painful stimuli, but results have been variable, and the functional relevance of any such activation is uncertain. The present study addresses this issue by testing whether the time course of somatosensory activation, evoked by painful heat and nonpainful tactile stimuli, is sufficient to discriminate temporal differences that characterize the perception of these stimulus modalities. Four normal subjects each participated in three functional magnetic resonance imaging (fMRI) sessions, in which painful (noxious heat 45-46 degrees C) and nonpainful test stimuli (brushing at 2 Hz) were applied repeatedly (9-s stimulus duration) to the left leg in separate experiments. Activation maps were generated comparing painful to neutral heat (35 degrees C) and nonpainful brushing to rest. Directed searches were performed in SI and SII for sites reliably activated by noxious heat and brush stimuli, and stimulus-dependent regions of interest (ROI) were then constructed for each subject. The time course, per stimulus cycle, was extracted from these ROIs and compared across subjects, stimulus modalities, and cortical regions. Both innocuous brushing and noxious heat produced significant activation within contralateral SI and SII. The time course of brush-evoked responses revealed a consistent single peak of activity, approximately 10 s after the onset of the stimulus, which rapidly diminished upon stimulus withdrawal. In contrast, the response to heat pain in both SI and SII was characterized by a double-peaked time course in which the maximum response (the 2nd peak) was consistently observed approximately 17 s after the onset of the stimulus (8 s following termination of the stimulus). This prolonged period of activation paralleled the perception of increasing pain intensity that persists even after stimulus offset. On the other hand, the temporal profile of the initial minor peak in pain-related activation closely matched that of the brush-evoked activity, suggesting a possible relationship to tactile components of the thermal stimulation procedure. These data indicate that both SI and SII cortices are involved in the processing of nociceptive information and are consistent with a role for these structures in the perception of temporal aspects of pain intensity.

Psychophysical analysis of visceral and cutaneous pain in human subjects.

Clinical evidence suggests that cutaneous and visceral pain differ in sensory, affective, and motivational realms, yet there has been little comparative characterization of these types of pain. This study uses psychophysical measures to compare directly visceral and cutaneous pain and sensitivity. Healthy subjects (10 males, seven females, age 19-29) evaluated perceptions evoked by balloon distention of the distal esophagus and contact heat on the upper chest. Subjects gave continuous ratings of pain intensity using an on-line visual analog scale (VAS), reported maximum pain intensity and unpleasantness on printed VASs, chose phrases from the McGill Pain Questionnaire and Spielberger State-Trait Anxiety Inventory, and drew the area of perceived sensation. For esophageal distention, the threshold for pain intensity was higher than that observed for unpleasantness, whereas for contact heat, pain and unpleasantness thresholds did not differ for either phasic (10s) or tonic (36s) stimulus application. The relative unpleasantness, calculated as the difference between the unpleasantness and the intensity ratings, was higher during esophageal distention than during either phasic or tonic cutaneous heat; this difference in relative unpleasantness was seen at all intensities of esophageal stimulation. Subjects chose significantly more affective words and reported more anxiety during visceral pain than during phasic cutaneous heat pain. A similar tendency was observed when visceral pain was compared to tonic cutaneous heat pain. Subjects also chose a wider range of words to describe visceral than cutaneous pain. On-line VAS ratings revealed greater pain sensation after stimulus termination during visceral than during phasic cutaneous pain; likewise, a similar tendency was observed between visceral and tonic cutaneous pain. Finally, visceral pain led to a more spatially diffuse sensation and was referred to the entire chest and sometimes to the back. Our results show that visceral pain is more unpleasant, diffuse, and variable than cutaneous pain of similar intensity, independent of the duration of the presented stimuli. The data suggest the likelihood of both similarities and differences in the neural substrates underlying visceral and cutaneous pain.

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.

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

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.