Spinal and supraspinal modulation of pain responses by hypnosis, suggestions, and distraction.

The mechanisms underlying pain modulation by hypnosis and the contribution of hypnotic induction to the efficacy of suggestions being still under debate, our study aimed, (1) to assess the effects of identical hypoalgesia suggestions given with and without hypnotic induction, (2) to compare hypnotic hypoalgesia to distraction hypoalgesia and (3) to evaluate whether hypnotic suggestions of increased and decreased pain share common psychophysiological mechanisms. To this end, pain ratings, nociceptive flexion reflex amplitude, autonomic responses and electroencephalographic activity were measured in response to noxious electrical stimulation of the sural nerve in 20 healthy participants, who were subjected to four conditions: suggestions of hypoalgesia delivered with and without hypnosis induction (i.e. hypnotic-hypoalgesia and suggested-hypoalgesia), distraction by a mental calculation task and hypnotic suggestions of hyperalgesia. As a result, pain ratings decreased in distraction, suggested-hypoalgesia and hypnotic-hypoalgesia, while it increased in hypnotic-hyperalgesia. Nociceptive flexion reflex amplitude and autonomic activity decreased during suggested-hypoalgesia and hypnotic-hypoalgesia but increased during distraction and hypnotic-hyperalgesia. Hypnosis did not enhance the effects of suggestions significantly in any measurement. No somatosensory-evoked potential was modulated by the four conditions according to strict statistical criteria. The absence of a significant difference between the hypnotic hypoalgesia and hyperalgesia conditions suggests that brain processes as evidenced by evoked potentials are not invariably related to pain modulation. Time-frequency analysis of electroencephalographic activity showed a significant differentiation between distraction and hypnotic hypoalgesia in the theta domain. These results highlight the diversity of neurophysiological processes underlying pain modulation through different psychological interventions.

Brain Responses to Hypnotic Verbal Suggestions Predict Pain Modulation.

Background: The effectiveness of hypnosis in reducing pain is well supported by the scientific literature. Hypnosis typically involves verbal suggestions but the mechanisms by which verbal contents are transformed into predictive signals to modulate perceptual processes remain unclear. We hypothesized that brain activity during verbal suggestions would predict the modulation of responses to acute nociceptive stimuli. Methods: Brain activity was measured using BOLD-fMRI in healthy participants while they listened to verbal suggestions of HYPERALGESIA, HYPOALGESIA, or NORMAL sensation (control) following a standardized hypnosis induction. Immediately after the suggestions, series of noxious electrical stimuli were administered to assess pain-related responses. Brain responses measured during the suggestions were then used to predict changes in pain-related responses using delayed regression analyses. Results: Listening to suggestions of HYPERALGESIA and HYPOALGESIA produced BOLD decreases (vs. control) in the parietal operculum (PO) and in the anterior midcingulate cortex (aMCC), and increases in the left parahippocampal gyrus (lPHG). Changes in activity in PO, aMCC and PHG during the suggestions predicted larger pain-evoked responses following the HYPERALGESIA suggestions in the anterior cingulate cortex (ACC) and the anterior insula (aINS), and smaller pain-evoked responses following the HYPOALGESIA suggestions in the ACC, aMCC, posterior insula (pINS) and thalamus. These changes in pain-evoked brain responses are consistent with the changes in pain perception reported by the participants in HYPERALGESIA and HYPOALGESIA, respectively. Conclusions: The fronto-parietal network (supracallosal ACC and PO) has been associated with self-regulation and perceived self-agency. Deactivation of these regions during suggestions is predictive of the modulation of brain responses to noxious stimuli in areas previously associated with pain perception and pain modulation. The response of the hippocampal complex may reflect its role in contextual learning, memory and pain anticipation/expectations induced by verbal suggestions of pain modulation. This study provides a basis to further explore the transformation of verbal suggestions into perceptual modulatory processes fundamental to hypnosis neurophenomenology. These findings are discussed in relation to predictive coding models.

HYPNOTIC AUTOMATICITY IN THE BRAIN AT REST: An Arterial Spin Labelling Study.

The feeling of automaticity reported by individuals undergoing a hypnotic procedure is an essential dimension of hypnosis phenomenology. In the present study, healthy participants rated their subjective experience of automaticity and resting-state arterial spin labelling (ASL) scans were acquired before and after a standard hypnotic induction (i.e., "neutral hypnosis"). The increase in perceived automaticity was positively associated with activity in the parietal operculum (PO) and seed-based coactivation analysis revealed additional associations in the anterior part of the supracallosal cingulate cortex (aMCC). This is consistent with the role of these regions in perceived self-agency and volition and demonstrates that these effects can be evidenced at rest, in the absence of overt motor challenges. Future studies should further examine if/how these changes in brain activity associated with automaticity might facilitate the responses to suggestions and contribute to clinical benefits of hypnosis.

Internal validity of inter-digital web pinching as a model for perceptual diffuse noxious inhibitory controls-induced hypoalgesia in healthy humans.

Hot and ice-water immersions are commonly used for heterotopic noxious counter-stimulation (HNCS) in investigations on endogenous pain modulation. However, coincident sympathetic thermoregulatory activity does not allow to differentiate between perceptual hypoalgesia related to baroreflex sensitivity (BRS) or diffuse noxious inhibitory controls (DNIC). The present study analysed the internal validity of another supposedly less confounded tonic pain model (inter-digital web pinching; IWP) regarding its potential as DNIC trigger. We performed a randomized controlled study in 24 healthy gender-matched drug-free volunteers aged 21-54 (median 25) years. The study protocol comprised the assessment of mechanical and thermal perceptual wind-up before and after an IWP (15N) or hot water immersion trial (HIT; 47.5°C) of 2 min duration. Wind-up was induced either by 10 repetitive (1Hz) contact heat (max. 49°C; 5×5 mm thermode) or ballistic impact stimuli (0.5g at 9 m/s) on the phalanges of the non-dominant hand. Cardiovascular activity, pain experience and corrugator muscle activity were continuously monitored. Although both HNCS forms produced a similar pain experience (45% of scale), a more pronounced cardiovascular activity was observable for the HIT (P<0.01). This indicates a higher baroreceptor activity and stronger contamination of painful water immersion by BRS-related hypoalgesia. Regardless of pain modality, wind-up was significantly reduced by HNCS, although this was stronger for painful water immersion than for noxious pinching (P<0.01). The HNCS types allow a differentiation between BRS-related and DNIC-like hypoalgesia. IWP proved its validity for DNIC induction, being practically non-confounded by BRS.

Differential physiological effects during tonic painful hand immersion tests using hot and ice water.

The cold pressor test (CPT) is an empirically validated test commonly used in research on stress, pain and cardiovascular reactivity. Surprisingly, the equivalent test with water heated to noxious temperatures (hot water immersion test, HIT) has not been thoroughly investigated. The aim of the present study was to characterize the physiological effects and psychophysics of both tests and to analyze whether the autonomic responses are mainly induced by baroreflexes or a consequence of the pain experience itself. The study consisted of a single session including one CPT (4+/-0.2 degrees C) and one HIT (47+/-0.5 degrees C; cut-off point 5 min) trial performed on 30 healthy drug free volunteers aged 19-57 (median 24) yrs. The sequence of both trials was alternated and participants were randomly assigned to sequence order and parallelized with respect to gender. Physiological parameters (cardiovascular, respiratory and electrodermal activity) and subjective pain intensity were continuously monitored. In addition, pain detection and tolerance thresholds as well as pain unpleasantness were assessed. Both tests were comparable with regard to the time course and intensity of subjective pain. However, a significantly higher increase of blood pressure could be observed during the CPT when compared to the HIT. The HIT appears less confounded with thermoregulatory baroreflex activity and therefore seems to be a more appropriate model for tonic pain.