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Virtual reality hypnosis (VRH) is a promising tool to reduce pain. However, the benefits of VRH on pain perception and on the physiological expression of pain require further investigation.
In this study, we characterized the effects of VRH on the heat pain threshold among adult healthy volunteers while monitoring several physiological and autonomic functions.
Sixty healthy volunteers were prospectively included to receive nociceptive stimulations. The first set of thermal stimuli consisted of 20 stimulations at 60°C (duration 500 milliseconds) to trigger contact heat evoked potentials (CHEPs). The second set of thermal stimuli consisted of ramps (1°C/second) to determine the heat pain threshold of the participants. Electrocardiogram, skin conductance responses, respiration rate, as well as the analgesia nociception index were also recorded throughout the experiment.
Data from 58 participants were analyzed. There was a small but significant increase in pain threshold in VRH (50.19°C, SD 1.98°C) compared to that in the control condition (mean 49.45°C, SD 1.87;
The results obtained in this study support the idea that VRH administration is effective at increasing heat pain thresholds and impacts autonomic functions among healthy volunteers. As a nonpharmacological intervention, VRH has beneficial action on acute experimental heat pain. This beneficial action will need to be evaluated for the treatment of other types of pain, including chronic pain.
Pain is an unpleasant sensory and emotional experience that is essential to the survival of living beings; however, its usefulness is lost if pain becomes chronic (duration>3 months) [
Fully immersive VR headsets isolate users from the “real world” and move them into an enjoyable alternative 3D virtual world. If well-executed, VR environments have the capability to reduce pain, as demonstrated by the pioneering work from Hoffman and collaborators [
Apart from modulation of the cortical nociceptive processing giving rise to the sensation of pain and its emotional value, pain motor responses may also be modulated in their somatic (conscious) or autonomic components. Because autonomic motor responses are less sensitive to subjective cues, they are often used in combination with other evaluation pain scales relying on subject impressions. The underlying mechanisms of VR action seem to be even more complex with the latest VR devices that often combine distracting visual cues with analgesia-promoting auditory sensory stimulations, ranging from passive listening of music to hypnotic suggestions [
In this study, we used virtual reality hypnosis (VRH), which combines the computer-generated immersive environment of VR with a hypnotic script [
Our hypothesis was that this VRH device, combining VR and hypnotic suggestions, increases pain thresholds, an effect that can possibly be predicted by cortical electrophysiological signatures and autonomic monitoring. Thus, the secondary objectives consisted of analyzing VRH-associated changes of several physiological biomarkers such as heart rate and heart rate variability, analgesia nociception index, respiratory rate, and skin conductance responses (SCRs) with and without VRH.
Sixty adult participants were included in the study (32 women and 28 men). Participants had to be affiliated with the French social security system, and could not participate if they had unbalanced epilepsy, psychotic disorders, depression, hearing and/or visual impairments preventing the use of VRH, or chronic diseases that may influence pain perception (eg, chronic pain, diabetes); if they were participating in another clinical study; were unable to provide informed consent; or refused to participate. Women could not participate if they were pregnant or breastfeeding.
This study was approved by the ethics review board of CPP OUEST IV-Nantes (approval date March 28, 2019; Agence Nationale de Sécurité du Médicament et des Produits de Santé, French Ministry of Health, information date May 7, 2019; IdRCB n° 2018-A02992-53). All participants signed a written informed consent form prior to participation.
This was an open, single-center, comparative, crossover study. Each participant performed the experiment in both the VRH and control (without VRH) conditions. To limit a potential order effect, the time of VRH application was randomly counterbalanced across participants. At the time of inclusion, suggestibility was assessed using the standardized Barber scale test [
For the experiment, the VR headset was an Oculus Rift (resolution: 1080×1200 pixels per eye; field of view: 110°; frame rate: 90 Hz) coupled to a laptop computer (Asus GL502VS managed by an IntelCore i7-6700HQ processor at 2.6 GHz; RAM: 16 GB; graphics card: Nvidia GeForce GTX 1070; Windows 10 64-bit). The sound was delivered by the Oculus Rift headset.
VRH was delivered through the HypnoVR application, coupling 3D immersive and dynamic visual scenery (walking on a beach or scuba diving) with a standardized prerecorded hypnotic script (including relaxing and analgesic suggestions available in several languages) as well as musical background following music therapy principles. The hypnotic script was the same for all environmental scenarios. The musical piece followed a U-shape sequence so that, together with visual experiences, it progressively helped the participants reach a state of cardiac coherence [
Thermal hot stimuli were applied with a thermal stimulator (TCS II, QST.Lab, Strasbourg, France) following the general scheme indicated in
Overview of the experimental protocol indicating 3 periods: virtual reality hypnosis induction, stimulation protocols with acute heat stimulation (for somatosensory event-related potential measures), and temperature ramps (for pain threshold determination). Arrows indicate the period of measurements of autonomic parameters. Two representative images of the virtual environment proposed to patients are shown. n corresponds to the number of subjects included in each analysis. ANI: analgesia nociception index; CHEP: contact heat evoked potential; ECG: electrocardiogram.
This session was followed by a second stimulation session used to evaluate heat pain thresholds, which was performed using the limit method with 10 ascending ramps. The temperature was increased at a rate of 1°C/second, from skin temperature (measured before the first ramp) to a temperature that volunteers considered as painful. Volunteers were given the instruction to stop the temperature increments with a push button when they felt that the stimulation was becoming painful. The pain threshold was assessed by averaging 10 trials. To take into account interindividual differences in skin temperature, the absolute pain threshold was measured as well as the difference between the skin temperature (measured just before the first ramp) and the absolute value of the threshold (Δ temperature). All participants were subjected to the hot stimulation sequence, enabling measurements of both CHEPs and pain thresholds with and without VRH. Stimuli occurred after a few minutes (maximum 7 minutes) of rest.
Cortical CHEPs (from electroencephalography [EEG] data) were recorded using Active Two AD-Box coupled with a 32–active electrodes cap respecting the 10/20 system (Biosemi). Ground electrodes (common mode sense and a driven right leg) were located between C3-Cz and between Cz-C4, respectively. The sampling frequency was set to 2048 Hz. EEG data were collected and monitored throughout the recording with Actiview version 8.0 (BioSemi B.V., WG-Plein 129, 1054SC). Raw data were preprocessed (offline) with Cartool software [
Physiological parameters were recorded with BIOPAC MP150 (BIOPAC System Inc). The electrocardiogram (ECG; beats/minute) was measured with BIOPAC ECG100C. The breathing rate (cycles/minute) was measured by a thermistor that determined the difference in temperature between inhaled and exhaled air (BIOPAC TSD202F). SCRs were measured from the extremities of the index and middle fingers of the dominant hand (BIOPAC TSD203). Acquisition was performed through a homemade software collecting and synchronizing data from the BIOSEMI and BIOPAC acquisition equipment. The sampling rate was set to 500 Hz for BIOPAC signals. Preprocessing of ECG included a 5th-order Butterworth high-pass filter of 0.5 Hz and a 50-Hz Notch filter. The detection of R-R peak intervals enabled extracting the percentage of successive R-R intervals that differ by more than 50 milliseconds (pNN50) and the root mean square of successive R-R interval differences (RMSSD) was calculated. A 3rd-order finite impulse response filter was applied to remove the electrical noise for SCR. A simple pic detection was performed for respiration data with no additional data treatment. ANI scores were calculated by the mDoloris monitor (MetroDoloris) following a previously reported method [
ECG, respiration, and SCR (all synchronized within one file) were epoched in a 1-minute-long file. Epoched data were analyzed with Clampfit (Molecular Devices) and Python 3.8 (especially the Neurokit library [
Data were prospectively collected using an audit form established for the study. All personal identifying information was removed from the database in accordance with regulations prescribed by the French data protection authority Commission Nationale de l’Informatique et des Libertés (CNIL 2213128). Collected data included the demographic characteristics (age, sex, education level) and if the participants had previously experienced motion sickness, as it might be a risk factor for nausea during VRH.
Results are expressed as mean (SD). The statistical analyses included a descriptive component and an analytical component. All statistical analyses were performed with GraphPad Prism software (version 6). The significance level was set at α=.05 for all analyses. Normality of the distributions was tested using the Shapiro-Wilk normality test. Differences between male and female participants in baseline characteristics were analyzed using the Mann-Whitney
A total of 60 participants fulfilled the inclusion criteria and were included in the study. Two participants (1 man and 1 woman) were excluded owing to incomplete data. Thus, 58 participants were included in the final analysis (
Most participants (40/58, 69%) did not previously suffer from travel sickness. The Barber suggestibility scores ranged from 0 to 7 out of a possible total of 8, with a mean of 3.2. Men and women had similar Barber suggestibility scores, demographic characteristics, and baseline measured variables, except for the STAI score and history of motion sickness, which were slightly higher in women. No adverse events were reported by any subject during the study.
Flow diagram of screened, randomized, and excluded participants.
Participant characteristics.
Characteristics | All participants (N=58) | Range (Total) | Women (n=31) | Men (n=27) | |
Age (years), mean (SD) | 30 (9.4) | 19-56 | 31 (10.4) | 29 (8.1) | .66a |
Education (years postbacb), mean (SD) | 4.3 (2.3) | 1-8 | 3.8 (2.6) | 4.8 (1.9) | .08a |
STAIc (score/80), mean (SD) | 37.8 (9.2) | 23-60 | 39.9 (8.6) | 35.3 (9.4) | .03a |
Barber (score/8), mean (SD) | 3.2 (1.6) | 0-7 | 3.3 (1.6) | 3.1 (1.6) | .65d |
Travel sickness history, n | 18 | N/Ae | 15 | 3 | .004f |
BMI, mean (SD) | 22.5 (7.0) | 18 – 32.4 | 21.9 (2.7) | 23.2 (3.3) | .13a |
aMann-Whitney
bAfter undergraduate college degree.
cSTAI: State-Trait Anxiety Inventory.
dUnpaired
eN/A: not applicable.
fFisher exact test.
As illustrated in
Effect of virtual reality hypnosis (VRH) on pain thresholds and somatosensory event-related potentials. A. Mean (SEM) absolute temperature before and after VRH. B. Mean (SEM) delta temperature (ie, the difference between the temperature threshold and skin temperature) in both conditions. C. Evolution of the mean (SEM) amplitude of N2-P2 (in µV) between control and VRH conditions. D. Superimposed mean traces of somatosensory event-related potentials obtained during VRH and without VRH, represented with their respective SDs. ***
We then measured CHEPs during the control and VRH conditions. Mean epoch traces for all participants with more than two successful trials in both conditions were retained in the analysis and are shown in
Mean values for heart rate, respiration rate, nonspecific SCR, heart rate variability parameters (ie, pNN50, RMSSD, and ANI) are shown in
The mean heart rate remained globally stable during the entire protocol, which was divided into a baseline period, a period corresponding to the intervals between the stimulation protocols, and a period occurring after the stimulation protocols. No differences were observed between the control and VRH conditions for each period (
Effect of virtual reality hypnosis (VRH) on autonomic parameters (mean, SEM). Mean heart rate (A), respiration rate (B), and nonspecific skin peak conductance (C) at baseline, during stimulation (Stim.; ie, between somatosensory event-related potential stimulations and ramps), and after the last stimulation (Post-Stim.) for the control and VRH conditions. D. Percentage of successive R-R intervals that differ by more than 50 milliseconds (PNN50) as an index of cardiac variability. E. Analgesia nociception index (ANI) for both conditions. *
This study investigated the effect of VRH on pain thresholds and CHEPs in response to heat stimuli in healthy adult volunteers (men and women). Changes in several physiological parameters were also monitored during the stimulation protocol. We found that VRH increased the heat pain threshold, reduced the mean respiratory rate during the VRH session, and increased the ratio between parasympathetic and sympathetic tones, as seen by the stability of SCR and the increase in ANI score.
Our findings are consistent with a recently published study, in which the authors measured the effect of VR on heat-pain tolerance limits [
Taking advantage of the simultaneous recording of some physiological parameters under VRH, we could observe significant changes of certain signals even though the nociceptive stimulations were of short duration. We observed a decrease in respiration rate and in SCR in VRH compared to the control condition, which confirmed the efficiency of the VRH script to promote relaxation and a possible decreased anxiety level that is known to reduce pain [
Compared to other VR devices, the VRH device used in this study includes not only visual and auditory immersive clues but also a hypnotic script following the classical hypnosis sequence for treatment purpose (ie, induction, dissociation, and suggestions of pain reduction). Hypnosis is an active cognitive treatment that allows the mind to influence sensations and perceptions of the body [
The main limitation of this study is linked to the experimental setup, as the hardware/software connections generated electrical artifacts in some cases so that the data from several participants could not be properly analyzed and were thus withdrawn from a specific analysis. Another limitation concerns the characteristics of the enrolled participants, who were healthy volunteers, highly educated, and of young age, which is not representative of the general population [
Collectively, the results of this study suggest that VRH has a small but significant beneficial effect on acute heat pain. This effect of VRH may involve multiple modulatory pathways, modifying the perception of pain and its expression through conscious and autonomic parameters, all leading to a better relaxation state. Acute or repeated use of VR might hence provide therapeutic benefits in patients suffering from pain, including when they are outside a hospital structure, as found in recent studies [
analgesia nociception index
Agence Nationale de la Recherche (French national research agency)
analysis of variance
contact heat evoked potential
electrocardiogram
electroencephalogram
percentage of successive R-R intervals that differ by more than 50 milliseconds
root mean square of successive R-R interval differences
skin conductance response
State-Trait Anxiety Inventory
virtual reality
virtual reality hypnosis
We thank the following research programs of excellence for their support: French National Research Agency (ANR) through the Programme d’Investissement d’Avenir (contract ANR-17-EURE-0022, EURIDOL Graduate School of Pain). PP received financial support from Institut Universitaire de France as a senior fellow. We thank Michel David for help with implementation of the research, along with Paolo Loureiro de Sousa and the staff of the “Imagerie, Robotique et Innovation pour la Santé (IRIS) “ICube” platform, Bâtiment “IRM 3T” of Strasbourg for their cooperation. We also thank Professor Kristian Torp for his thorough review. The project was supported by “Grand Est” regional funding and FEDER as part of the 2017 call for expressions of interest “Digital Economy.” The following program and institutional partners also contributed from the Centre National de la Recherche Scientifique, Université de Strasbourg. CT is supported by a PhD scholarship from the Conventions Industrielles de Formation par la Recherche program coordinated by the Association Nationale pour la Recherche et la Technologie.
Study conception: CC, DG, EL, SF, LG; Data acquisitions and analysis: CT, LG, SF, AD, PP, MM; Article writing: CT, MM, CC, PP; Funding acquisition: EL, CC, PP, SF, DG.
CC and DG hold a pending patent for the software HypnoVR used in this study. AD holds a pending patent for the thermal stimulator used in this study. The other authors report no conflict of interest related to this work.