Pain-reduction strategies in hypnotic context and hypnosis: ERPs and SCRs during a secondary auditory task

Pain-rating scores were obtained from 10 high, 10 medium, and 10 low hypnotizable subjects who were holding a painful cold bottle in their left hands and were exposed to pain reduction treatments while they were performing a secondary oddball task. All subjects received suggestions of dissociative imagery and focused analgesia as cognitive strategies for pain reduction. The following measures were obtained for tone targets of the auditory oddball task: (a) reaction time; (b) P300 peak amplitude of the event-related potentials; (c) skin conductance levels and skin conductance responses. Focused analgesia produced the most pain reduction in high, but not medium or low, hypnotizable subjects who showed shorter reaction times, higher central and parietal P300 peaks, and higher skin conductance responses. These findings were discussed vis-a-vis the dissociated-control model assuming that capacity demands of hypnotic suggestion are low.     

Focused analgesia in waking and hypnosis: effects on pain, memory, and somatosensory event-related potentials

Somatosensory event-related potentials (SERPs) to painful electric standard stimuli under an odd-ball paradigm were analyzed in 12 high hypnotizable (HH), 12 medium hypnotizable (MH), and 12 low hypnotizable (LH) subjects during waking, hypnosis, and a cued eyes-open posthypnotic condition. In each of these conditions subjects were suggested to produce an obstructive imagery of stimulus perception as a treatment for pain reduction. A No-Analgesia treatment served as a control in waking and hypnosis conditions. The subjects were required to count the number of delivered target stimuli. HH subjects experienced significant pain and distress reductions during posthypnotic analgesia as compared to hypnotic analgesia and between these two analgesic conditions as compared to the two control conditions. Outside of hypnosis, these subjects remembered less pain and distress levels than they reported during hypnotic and posthypnotic analgesia treatments. In contrast, for waking-analgesia treatment, HH subjects remembered similar pain and distress levels to those they reported concurrently with the stimulation. HH subjects, during hypnotic and posthypnotic analgesia treatments, detected a smaller number of target stimuli and displayed a significant amplitude reduction of the midline frontal and central N140 and P200 SERP components. No significant SERP differences were observed for these subjects between treatments in waking condition and between hypnotic and posthypnotic analgesic treatments. For the MH and LH subjects no significant N140 and P200 amplitude changes were observed among analgesic conditions as compared to control conditions. These amplitude findings are seen as indicating that hypnotic analgesia can affect earlier and later stages of stimulus processing.     

Pain perception, somatosensory event-related potentials and skin conductance responses to painful stimuli in high, mid, and low hypnotizable subjects: effects of differential pain reduction strategies

In this study, pain perception, somatosensory event-related potential (SERP) and skin conductance response (SCR) changes during hypnotic suggestions of Deep Relaxation, Dissociated Imagery, Focused Analgesia, and Placebo, compared with a Waking baseline condition, were investigated. SERPs were recorded from frontal, temporal, central, and parietal scalp sites. Ten high, 9 mid, and 10 low hypnotizable right-handed women participated in the experiment. The following measures were obtained: (1) pain and distress tolerance ratings; (2) sensory and pain thresholds to biphasic electrical stimulation delivered to the right wrist; (3) reaction time and number of omitted responses; (4) N2 (280+/-11 ms) and P3 (405+/-19 ms) peak amplitudes of SERPs to target stimuli delivered using an odd-ball paradigm; (5) number of evoked SCRs and SCR amplitudes as a function of stimulus repetition. Results showed, high, mid and low hypnotizables exhibited significant reductions of reported pain and distress ratings during conditions of Deep Relaxation/Suggestion of Analgesia, Dissociated Imagery and Focused Analgesia. High hypnotizable subjects displayed significant reductions in pain and distress levels compared to mid and low hypnotizables during Dissociated Imagery, Focused Analgesia and, to a lesser degree, during Deep Relaxation. Placebo condition did not display significant differences among hypnotizability groups. High hypnotizables, compared to mid and low hypnotizables, also showed significant increases in sensory and pain thresholds during Dissociated Imagery and Focused Analgesia. High, mid, and low groups showed significant reductions in P3 peak amplitudes across all hypnosis conditions and, to a lesser degree, during Placebo. The temporal cortical region was the most sensitive in differentiating SERP responses among hypnotizability groups. On this recording area the subjects highly susceptible to hypnosis displayed significantly smaller P3 and greater N2 peaks during Focused Analgesia than did the other hypnotizable groups. In this condition highly susceptible subjects also reported the highest number of omitted responses and the shortest Reaction Times. These subjects also showed faster habituation of SCRs when compared with mid and low hypnotizables. During Dissociated Imagery and Focused Analgesia, highly hypnotizable subjects also disclosed a smaller total number of evoked SCRs than did mid and low hypnotizable subjects. The results are discussed considering possible common and different mechanisms to account for the effects of different hypnotic suggestions.     

AUDITORY EVOKED POTENTIALS EVIDENCE FOR DIFFERENCES IN INFORMATION PROCESSING BETWEEN HIGH AND LOW HYPNOTIZABLE SUBJECTS

N100 and P300 auditory evoked potentials in 2-stimulus oddball paradigm were analyzed in high (HH, n = 18) and low (LH, n = 15) hypnotizable participants under waking condition. LH subjects committed more errors than HH subjects. HH subjects demonstrated shorter N100 latencies at frontal electrodes and significant N100 differences between target and nontarget stimuli (higher N100 amplitude and increased latency at parietal sites to targets vs. nontargets), whereas LH subjects failed to show any differences. The overall increase of P300 amplitude with frontal-central localization of P300 maximum was found in HH subjects compared to LH subjects. The obtained results support the psychophysiological model of HH individuals having more effective frontal attentional systems involved in detecting, integrating, and filtering relevant information.     

Perception and modulation of pain in waking and hypnosis: functional significance of phase-ordered gamma oscillations

Somatosensory event-related phase-ordered gamma oscillations (40-Hz) to electric painful standard stimuli under an odd-ball paradigm were analyzed in 13 high, 13 medium, and 12 low hypnotizable subjects during waking, hypnosis, and post-hypnosis conditions. During these conditions, subjects received a suggestion of Focused Analgesia to produce an obstructive hallucination of stimulus perception; a No-Analgesia treatment served as a control. After hypnosis, a post-hypnotic suggestion was given to draw waking subjects into a deep hypnosis with opened eyes. High hypnotizables, compared to medium and low ones, experienced significant pain and distress reductions for Focused Analgesia during hypnosis and, to a greater extent, during post-hypnosis condition. Correlational analysis of EEG sweeps of each individual revealed brief intervals of phase ordering of gamma patterns, preceding and following stimulus onset, lasting approximately six periods. High and medium hypnotizable subjects showed significant reductions in phase-ordered gamma patterns for Focused Analgesia during hypnosis and post-hypnosis conditions; this effect was found, however, more pronounced in high hypnotizable subjects. Phase-ordered gamma scores over central scalp site predicted subject pain ratings across Waking-Pain and Waking-Analgesia conditions, while phase-ordered gamma scores over frontal scalp site predicted pain ratings during post-hypnosis analgesia condition. During waking conditions, this relationship was present in high, low and medium hypnotizable subjects and was independent of stimulus intensity measures. This relationship was unchanged by hypnosis induction in the low hypnotizable subjects, but not present in the high and medium ones during hypnosis, suggesting that hypnosis interferes with phase-ordered gamma and pain relationship.     

Effects of hypnotic analgesia and hypnotizability on experimental ischemic pain

Mechanisms of hypnotic analgesia are still poorly understood and conflicting data are reported regarding the underlying neurochemical correlates. The present study was designed to investigate the effects of hypnotically induced analgesia and hypnotizability on experimental ischemic pain, taking into account pain and distress tolerance as well as the neurochemical correlates. 11 high hypnotizable Ss and 10 low hypnotizable Ss, as determined by scores on the Stanford Hypnotic Susceptibility Scale, Form C (Weitzenhoffer & E. R. Hilgard, 1962), were administered an ischemic pain test in both waking and hypnotic conditions. The following variables were measured: (a) pain and distress tolerance, (b) anxiety levels, and (c) plasma concentrations of beta-endorphin and adrenocorticotropic hormone (ACTH). Results confirmed significant increases of pain and distress tolerance during hypnosis as compared to the waking state, with positive correlations between pain and distress relief and hypnotizability. Moreover, a hypnotically induced dissociation between the sensory-discriminative and the affective-motivational dimensions of pain experience was found, but only in high hypnotizable Ss. Hypnotic analgesia was unrelated to anxiety reduction and was not mediated either by endorphins or by ACTH.     

A functional MRI study of visual oddball: evidence for frontoparietal dysfunction in subjects at risk for alcoholism

Attending to rare stimuli interspersed among repetitive frequent stimuli produces a positive scalp potential at 300 to 600 ms after the target stimulus onset; this potential is known as the P300 wave. Although there is clear evidence of low visual P300 in subjects at high risk (HR) for developing alcoholism, the functional neuroanatomical correlates have not been studied. Functional and high-resolution anatomical magnetic resonance images were collected during the performance of a visual oddball task, from six control (low risk-LR) subjects with high P300s and eight HR subjects with low P300s. All the HR subjects were offspring of male alcoholics. The data were analyzed using a randomization-based statistical method that accounts for multiple comparisons, requires no assumptions about the noise structure of the data, and does not require spatial or temporal smoothing. Target counts showed that all subjects performed the task comparably. Analysis of the functional magnetic resonance imaging (fMRI) data revealed two areas with significantly lower activation in the HR group when compared to the LR group: the bilateral inferior parietal lobule (BA 40), and the bilateral inferior frontal gyrus (BA 44). Inferior parietal lobule showed significantly lower activation in the HR group in contrast to the LR group, and inferior frontal gyrus was not activated in the HR group but was only activated in the LR group. This finding indicates that a dysfunctional frontoparietal circuit may underlie the low P300 responses seen in HR subjects. This perhaps implies a deficiency in the rehearsal component of the working memory system.     

Autonomic indices and reactive pain reports on the McGill Pain Questionnaire

Skin conductance and heart rate measures obtained from subjects previous to, during, and after their performance of the cold pressor task were correlated with their responses to the McGill Pain Questionnaire administered immediately after the completion of the cold pressor task. A reliable relationship between skin conductance level and responses on the evaluative scale of the MPA was found in the resting state, while anticipating the cold pressor task and during this task. Heart rate was related to these pain reports only during the warning or anticipation period. These findings were interpreted as supporting the use of the McGill Pain Questionnaire in the assessment of the reactive component of pain. They also suggest the utility of further research into autonomic indices as physiological correlates of this reactive aspect of pain.     

Effects of an opioid antagonist on pain intensity and withdrawal reflexes during induction of hypnotic analgesia in high- and low-hypnotizable volunteers

The aim of this investigation was to study the effect of suggestions of hypnotic analgesia on spinal pain transmission and processing. Pain intensity and amplitude of nociceptive withdrawal reflexes to electrical stimuli were measured in 10 high- and 10 low-hypnotizable subjects during two sessions taking place at least 24 h apart under five conditions of. (1) pre-hypnosis; (2) neutral hypnotic relaxation; (3) suggestions of hypnotic analgesia; (4) suggestions of hypnotic analgesia after injections of either naloxone (1 ml, 1 mg/ml) or saline (1 ml) under double-blinded conditions; and (5) post-hypnosis. The conditions of naloxone or saline were allocated at random to either Day 1 or Day 2 in a double-blinded fashion. Results showed significant reductions of pain intensity during hypnotic analgesia, and a significant reduction in nociceptive reflexes during hypnotic analgesia on Day 1 in the highly hypnotizable group. No differences were found for low-hypnotizable subjects. The results support previous findings that pain intensity as well as the nociceptive reflex can be modulated by suggestions of hypnotic analgesia. While no effect of naloxone on pain intensity was found during hypnotic analgesia, naloxone significantly reversed the suppressive effect of suggestions of hypnotic analgesia on reflexes in high-hypnotizable subjects. Subsequent analysis showed that the effect of naloxone was associated with the intensity of the stimulus needed to elicit a reflex, and was unrelated to hypnotic susceptibility when controlling for stimulus intensity. These results suggest that the effect of naloxone was related to the greater stimulus intensities needed to elicit a reflex in the high-hypnotizable group, rather than to hypnosis or hypnotic susceptibility in itself. It is unclear why greater stimulus intensities were needed in high-hypnotizable subjects and further studies are needed.     

Physiological Responsiveness During Hypnosis

4 physiological measures — electromyogram, respiration rate, heart rate, and skin conductance — were recorded for 11 high and 11 low hypnotizable Ss. It was hypothesized (a) that physiological responsiveness during hypnosis would vary depending on the nature of the task instructions, and (b) that high hypnotizable Ss would show more physiological responsiveness than low hypnotizable Ss. The first hypothesis was substantiated across all 4 measures. Only heart rate levels supported the second hypothesis. The results are discussed as they relate to the 2 hypotheses and to future research.     

Pain measurement with evoked potentials: combination of subjective ratings, randomized intensities, and long interstimulus intervals produces a P300-like confound

Evoked potentials in response to painful stimuli have been studied as objective measures of pain. Bromm has advocated experimental conditions in which, (1) stimulus intensities are randomized, and (2) subjects rate each stimulus. However, a cognitive, i.e. information processing, 'late positive component' (LPC), e.g. the P300, may be elicited by these same conditions, whether or not the stimuli are painful. The LPC may overlap, and interfere with the measurement of, responses that are only seen with painful stimuli. We compared the LPC in two experimental protocols using ten subjects and electrical stimuli. In the 'Rating Protocol', shocks of different intensity levels were randomly presented and subjects rated the intensity of each stimulus. In the 'Oddball Standards Protocol', the same levels were used, but each was presented in a separate block of a single level. Stimuli were presented more rapidly and subjects had to push a button in response to occasional double shocks (oddball targets), but not to single shocks (oddball standards). The oddball targets served to direct subjects' attention to the stimuli, but only the evoked potential responses to the oddball standards were used for data analysis. To look at the difference between protocols, we computed a difference condition (Rating protocol responses minus Oddball Standards protocol responses) which we called Incremental activity. The Incremental LPC (average amplitudes from 350 to 650 ms) had a more parietal topography (amplitude at electrode Pz greater than at Cz) than the Oddball Standards LPC (Cz > Pz; protocol x electrode interaction P<0.001). This implies that the Rating Protocol LPC included P300-like activity. The parietal Incremental activity began as early as 250-350 ms after the stimulus in the responses to the most painful stimuli and therefore can confound the measurement of pain activity in the evoked potential.     

Parental history of chronic pain may be associated with impairments in endogenous opioid analgesic systems

A family history of chronic pain has previously been linked to increased incidence of spontaneous acute pain and risk for chronic pain. Mechanisms underlying these associations are unknown, although similar effects on both acute and chronic pain suggest that central endogenous analgesic system differences may be relevant. This study tested whether a positive parental chronic pain history (PH+) was associated with impaired endogenous opioid analgesic responses to acute pain. Seventy-three chronic low back pain patients (LBP) and 46 pain-free controls received opioid blockade (8mg naloxone i.v.) and placebo blockade (saline) in randomized, counterbalanced order in separate sessions. During each, subjects participated in a 1-min finger pressure pain task followed by an ischemic forearm pain task, providing pain intensity ratings during and immediately following each task. To assess opioid analgesic function, blockade effects were derived by subtracting placebo from blockade condition pain responses. Placebo condition analyses indicated that both PH+ subjects and LBP subjects reported greater acute pain sensitivity than respective comparison groups (p's<.05). Multivariate analyses indicated that, beyond any influence of current chronic pain status, PH+ subjects failed to exhibit any endogenous opioid analgesia to acute ischemic pain, whereas PH- subjects elicited effective opioid analgesia (p<.05). A significant multivariate PHxSubject Type interaction (p<.05) indicated that opioid analgesic impairments were most prominent in PH+ LBP subjects. Similar analyses for finger pressure pain blockade effects were nonsignificant (p>.10). The possible heritability of endogenous opioid analgesic dysfunction observed in individuals with a positive parental chronic pain history remains to be investigated.     

Sensory and affective dimensions of phasic pain are indistinguishable in the self-report and psychophysiology of normal laboratory subjects.

This study evaluated the discriminant validity of subjects differentially scaling the sensory and affective dimensions of pain. It sought to determine (1) whether subjects can differentially scale sensory and affective aspects of phasic laboratory pain in the absence of task demand bias that fosters apparent differential scaling; (2) whether psychophysiologic responses to painful stimuli can predict pain report (PR); and (3) whether such responses contribute more to affective than to sensory judgments. Fifty-six men and 44 women repeatedly experienced varied painful electrical fingertip stimuli at low, medium, and high intensities. On half of the trial blocks, subjects made sensory judgments; on the remainder they made affective judgments. Response measures included PR, pupil dilation, heart rate, respiration rate, skin conductance response (SCR), and late near field evoked potentials. Subjects did not rate the stimuli differently when making sensory versus affective judgments. The psychophysiologic variables, principally the SCR, accounted for 44% of the variance in the PR. Psychophysiologic response patterns did not differentiate affective and sensory judgment conditions. Noteworthy sources of individual differences included baseline PR levels and the linear effects of SCR on PR.     

Modulation of pain-induced endothelial dysfunction by hypnotisability

Mental stress induces endothelial dysfunction, that is a reduction of the post-occlusion brachial artery flow-mediated vasodilation (FMD). This does not occur in subjects highly susceptible to hypnosis (Highs) in either the waking or hypnotic state. The aim of the present experiment was to assess whether endothelial dysfunction is also induced by acute nociceptive stimulation and whether high hypnotisability and/or the specific instruction of analgesia prevent its occurrence in awake highly hypnotizable individuals. Thus, nine Highs and nine subjects with low susceptibility to hypnosis (Lows) underwent an experimental session including the administration of pressor pain and of pressor pain associated with the instruction of analgesia. Heart rate, basal artery diameters and brachial artery flow-mediated vasodilation were measured during stimulation and rest conditions. Heart rate exhibited slight changes not modulated by hypnotisability. During painful stimulation both Highs and Lows showed a decrease of FMD, but it was significantly less pronounced in Highs. During the administration of painful stimulation together with the instruction of analgesia, only Highs reported analgesia and their FMD no longer decreased. This study provides the first evidence of pain-related endothelial dysfunction and extends previous findings concerning a sort of natural protection of Highs against the vascular effects of mental stress to acute pain.     

Altered pain processing in children with migraine: An evoked potential study

In adults, evidence is accumulating that migraine is associated with altered central processing of pain stimuli and, possibly, changes in the allocation of attentional resources to such stimuli. In pediatric migraine, however, little is known about altered pain processing. We examined 15 children with migraine and 15 controls (age 10–15) in an oddball standards task. Children had to respond to rare targets (tones) and ignore frequent painful (pain threshold) or non‐painful mechanical standard stimuli while evoked potentials were obtained. Painful as compared to non‐painful stimuli elicited significantly larger N150, P260 and P300 components of the somatosensory evoked potential in all children. The pain‐evoked N150 and P260 components did not differ significantly between groups. However, in children with migraine, both painful and non‐painful standard stimuli were associated with significantly larger P300 amplitudes at significantly shorter latencies. Perceived intensity of the painful and non‐painful stimuli was comparable in both groups. The evoked potentials and reaction times to the target tones did not differ significantly between groups. Habituation across trials was similar in both groups. Hence, children with migraine may display an automatic attentional bias towards painful and potentially painful somatosensory stimuli. Consistent with the psychobiological perspective of chronic pain, such an attentional bias could constitute an important mechanism for migraine becoming a chronic problem.     

Motor imagery during hypnotic arm paralysis in high and low hypnotizable subjects.

Previous research suggests that conversion disordered patients with hand/arm paralysis exhibit slowed reaction times for mental hand-rotation tasks that correspond to their affected arm when the tasks are explicitly instructed and not when they are implicitly cued. Because of the many similarities between hypnotic phenomena and conversion symptoms, the authors tested whether similar motor imagery impairment would occur among normal high hypnotizable subjects when paralysis is suggested. Nine high and 8 low hypnotizable subjects were administered an implicit and an explicit mental hand-rotation task during hypnotically suggested paralysis of the right arm. On the implicit task, there were no significant reaction time (RT) differences between highs and lows. On the explicit task, only highs showed a significantly larger RT increase per degree of rotation with the paralyzed arm, compared to the normal arm. These preliminary findings suggest that the motor imagery impairment observed in conversion paralysis can be induced in highs using hypnosis.     

Variability in placebo analgesia and the role of fear of pain--an ERP study

Fear of pain (FOP) and its effect on placebo analgesia was investigated. It was hypothesized that FOP should interfere with placebo-mediated pain inhibition and result in weaker placebo responding in pain intensity, pain unpleasantness, stress, and event-related potentials to contact heat pain. Thirty-three subjects participated in a balanced 2 condition (natural history, placebo) × 3 test (pretest, posttest 1, posttest 2) within-subject design, tested on 2 separate days. FOP was measured by the Fear of Pain Questionnaire and subjective stress by the Short Adjective Check List. Placebo effects were found on reported pain unpleasantness and N2 and P2 amplitudes. FOP was related to reduced placebo responding in pain unpleasantness, but this was only evident for the subjects who received the placebo condition on day 1. Subjects who received the placebo condition on day 1 experienced more pretest stress than those who received the placebo condition on day 2 (ie, reversed condition order), and this explained the interaction effect on placebo responding. FOP was related to reduced placebo responding on P2 amplitude, whereas placebo responding on N2 amplitude was unaffected by FOP. Higher placebo responses on N2 and P2 amplitudes were both related to higher placebo analgesic magnitude in pain unpleasantness. In conclusion, increased FOP was found to reduce subjective and electrophysiological placebo analgesic responses.     

Parametric trial-by-trial prediction of pain by easily available physiological measures

Pain is commonly assessed by subjective reports on rating scales. However, in many experimental and clinical settings, an additional, objective indicator of pain is desirable. In order to identify an objective, parametric signature of pain intensity that is predictive at the individual stimulus level across subjects, we recorded skin conductance and pupil diameter responses to heat pain stimuli of different durations and temperatures in 34 healthy subjects. The temporal profiles of trial-wise physiological responses were characterized by component scores obtained from principal component analysis. These component scores were then used as predictors in a linear regression analysis, resulting in accurate pain predictions for individual trials. Using the temporal information encoded in the principal component scores explained the data better than prediction by a single summary statistic (ie, maximum amplitude). These results indicate that perceived pain is best reflected by the temporal dynamics of autonomic responses. Application of the regression model to an independent data set of 20 subjects resulted in a very good prediction of the pain ratings demonstrating the generalizability of the identified temporal pattern. Utilizing the readily available temporal information from skin conductance and pupil diameter responses thus allows parametric prediction of pain in human subjects.     

Separating neural and vascular effects of caffeine using simultaneous EEG-FMRI: differential effects of caffeine on cognitive and sensorimotor brain responses

The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A(1) and A(2A) adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG-FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19% reduction over grey matter). We were able to identify vascular effects and hence altered neurovascular coupling through the alteration of low-level task FMRI responses in the face of a preserved visual evoked potential. However, our data also suggest a cognitive effect of caffeine through its positive effect on the frontal BOLD signal consistent with the shortening of oddball EEG response latency. The combined use of EEG-FMRI is a promising methodology for investigating alterations in brain function in drug and disease studies where neurovascular coupling may be altered on a regional basis.