Pain is shaped by the context, meaning and the individual's psychological state (1). While the sensory component of pain (e.g., its intensity) refers to the physical sensation evoked by tissue damage or injury, the emotional component (e.g., its unpleasantness) is equally important and can significantly influence a person's pain experience (2). Most people recover from pain following an injury or operation and return to normalcy. However, there are situations when the pain lasts longer or appears suddenly without any prior history of an accident or operation. Pain that persists for more than 12 weeks despite medication or treatment is referred to as chronic or short-term pain (3). In terms of pharmacological treatment, several classes of medications have demonstrated efficacy in relieving pain, including antidepressants, certain anticonvulsants, opioids and non-steroidal anti-inflammatory drugs (4–7). However, the efficacy of some of these treatments is mixed (anticonvulsants), and some have potentially serious side effects (opioids). Among non-pharmacological pain treatments, virtual reality (VR) is one of the modalities that has attracted the most research interest over the past decade. Its potential efficacy has been tested in a wide range of painful conditions, from post-operative pain and neuropathic pain to pediatric pain and pain associated with medical procedures (4–7). To date, most clinical trials have included small samples and the proposed interventions have generally been offered over short periods of time. Despite these limitations, virtual reality has produced highly promising results, especially in the case of immediate pain (8), certainly justifying further work in this area.

To gain a better understanding of the potential mechanisms of action of virtual reality, several experimental studies have been carried out in healthy volunteers, using psychophysical procedures to administer nociceptive stimuli in a controlled manner. Regardless of the modality used (thermal, mechanical stimulation, etc.), the vast majority of studies to date have shown that virtual reality produces analgesic effects in a laboratory setting (9–12). Although promising, these studies have significant limitations. In most cases, they have focused on pain intensity, without addressing the unpleasantness of pain (13–15). More importantly, studies in the field often lack of an active control condition (i.e., non-immersive VR) (16). Indeed, in most studies, the control condition was a simple baseline condition where participants were asked to look at a blank screen (9, 11, 17). This is an important limitation which makes it difficult to properly interpret findings considering that such studies cannot rule out the possibility that simply wearing a head mounted display (HMD; with no VR content) may be sufficiently distracting to produce analgesic effects. It is important to point out, however, that a few studies have used minimal control conditions (example: HMD showing a black screen) and have shown that VR environments produce greater analgesic effects (18).

For this pilot study, we used a VR environment that was initially developed for the treatment of endometriosis, a chronic inflammatory disease defined by the presence of endometrial tissue outside the uterus, causing pelvic pain and infertility (19, 20). This VR environment, known as Endocare, consists in a session during which patients are immersed in a playful, calming environment (e.g., a landscape consisting of water and a beach). During the session, the background sound is made up, among other things, of binaural beats, for which the relaxing effects have been demonstrated (21). As compared to other VR interventions, the tool was not designed to primarily produce attention-grasping effects. The efficacy of this VR environment has been evaluated in a randomized controlled trial of endometriosis patients (22). The analgesic effects persisted for 4 h after administration. As such, the persistency of analgesic effects suggests that the VR environment recruits endogenous pain inhibition mechanisms. This echoes the results of a recent experimental study (23) which tested a VR environment on 38 volunteers and found that it was possible to directly enhance the endogenous pain inhibition efficacy in healthy volunteers.

Several psychological factors are commonly associated with pain across different pathologies, and some studies showed that we can predict treatment response with these variables in both clinical and non-clinical populations (24–26). In fact, according to a meta-analysis, 16 studies involving healthy volunteers reported a predictive relationship between psychological factors and experimental pain, while seven showed variable results (27). Such psychological factors include pain catastrophizing, sleep quality, anxiety, the severity of the pain and its impact on functioning (28, 29). A systematic review (30) on the use of VR as a distraction technology emphasized the role of several psychological aspects in the efficacy of analgesic distraction. The sense of presence is another key element influencing the efficacy of VR as diversion techniques (31, 32), with greater sense of presence being generally associated with greater treatment response. Finally, in the search of individual characteristics predicting treatment response in the field of pain, psychophysical procedures are growingly used. Thus far, it has been shown that one of the best predictors of pain outcomes is the efficacy of endogenous pain inhibition mechanisms including inhibitory conditioned pain modulation (33, 34).

To gain a better understanding of the mechanisms involved in a novel immersive digital tool that was developed for the treatment of endometriosis, we carried out an experimental pilot study in healthy volunteers. A randomized cross-over design was adopted, and pain was elicited using tonic thermal noxious stimuli. Considering that experimental studies that have tested VR interventions have focused mostly on pain intensity, and that control conditions have been inadequate in most cases, the current pilot study measured pain unpleasantness and used an active control condition. More precisely, we aimed to compare a 3D environment with sound (e.g., binaural beats) to a 2D environment with no sounds, both projected in a VR headset. Since the novel tool appears to produce clinical benefits that persist over time, pain outcomes were measured both during and after the administration of the VR environment. A secondary objective of the study was to identify the psychological and psychophysical factors that predict the analgesic effects of the immersive digital therapeutic tool.

The main objective of the current experimental pilot study was to examine the effect of a VR environment on experimental pain in healthy volunteers to gain a better understanding of its mechanisms of action, while paying attention to both pain intensity and pain unpleasantness. Both the immediate and short-term effects of the VR environments were tested, and a minimally active control condition was used. Results showed an immediate effect of the VR environment on pain unpleasantness but no short-term effect. The analgesic efficacy of the VR environment on pain unpleasantness did not correlate with any of the psychological and physiological (e.g., iCPM) variables measured.

The main finding of the current study is that the VR environment produced a specific effect on the emotional component of pain, with no observed effect on its sensory-discriminative component. This finding is coherent with the evidence pointing to significant differences between these two pain components. First, there reliable is evidence that these two components are processed by different brain regions (50). Moreover, there is evidence demonstrating that pain intensity and unpleasantness may exhibit divergent responses to certain analgesic procedures such as transcutaneous electric nerve stimulation, hypnosis and opioids (51–55). One of the potential explanations for this specific effect on pain unpleasantness has to do with the fact that binaural beats are included in the immersive digital tool. Although there is no agreement upon the mechanisms underlying binaural auditory beats, there is a growing support for the claim that binaural auditory beats affect psychophysiological states. Indeed, numerous studies have reported that binaural beats exposure leads to a change in pain perception, autonomic measures and negative emotions, and is known to produce a relaxing effect (56–58). Another explanation would be the exposure to visual stimuli from nature (e.g., sand, water, trees, mountains) and nature-based sounds that are displayed in the VR environment. Multiple studies have shown that both nature-based auditory and visual stimuli can reduce stress and anxiety and produce pain relief (59–65). The specific effect on pain unpleasantness of the VR environment in the current study is relevant for the design of future trials using this immersive digital tool. It does suggest, indeed, that the VR environment should be primarily tested in chronic pain populations with significant levels of distress. While anxio-depressive symptoms are usually quite prevalent in chronic pain (66, 67), the comorbidity rates are even higher in chronic pain conditions with no clear physiological causes, such as functional pain syndromes (68).

Although this was not directly tested, the results observed here do not suggest that the VR environment activated endogenous pain inhibition mechanisms (e.g., iCPM). Indeed, no correlation was observed between the effect of the environment on pain unpleasantness and iCPM; moreover, these beneficial effects of the VR environment were only observed during the immediate administration, without these effects persisting after its interruption. As such, these results are inconsistent with the previous clinical study with the immersive digital tool which has highlighted, in endometriosis patients, analgesic effects that lasted up to 4 h after the environment administration (22). There are two possible explanations for this discrepancy in results between the two studies. On the one hand, the previous clinical study involved people with chronic pain, whereas the present study included healthy volunteers with no clinical pain. It is therefore possible that the effect of the immersive digital tool may differ depending on whether the pain is iatrogenic or experimentally induced. The other point to consider is that in the previous study, pain measurements were taken for a long period of time (4 h) after the VR environment was discontinued, whereas in the present study, we took only one measurement, immediately after the VR environment was discontinued. The limited duration of the after-treatment measurement may have prevented the observation of delayed analgesic effects. Significant improvements may have only been observable with longer time frames.

Contrary to our expectations, we did not observe any correlations between the analgesic effect of the VR environment and the various clinical variables measured in the project, namely anxiety, sub-clinical pain, pain catastrophizing, and sleep. As such, this lack of correlation is inconsistent with past studies conducted with clinical populations or healthy volunteers tested in experimental settings (69, 70). The main reason for this lack of correlation in the present study could be explained by the fact that our study included a non-clinical sample. The recruited sample presented rather low levels of anxiety, sub-clinical pain, pain catastrophizing and sleep problems as compared to normative and clinical samples (35, 38, 41, 43, 44, 46).

One of the strengths of this pilot study is that the control condition was immersive in that participants had to wear the VR headset during this condition. This procedure markedly contrasts with many past studies in the field that used simple baseline conditions (63, 71, 72). The use of a minimally active control condition in the current experimental study is important in that it allowed to control for mere effects of wearing a VR headset. Despite this important methodological strength, the present study had some limitations. As mentioned previously, one of the limitations of the current study is that only one pain measurement was taken immediately at the end of the administration of the experimental and control conditions. Another limitation is the sample size (N = 21), which was relatively small. Small samples are associated with decreased statistical power. This increases the likelihood of committing type II errors, where smaller effects are not detected due to insufficient data. The inclusion of a small number of participants also makes populational inferences more uncertain. Finally, we acknowledge that the use of the BPI for measuring transient painful somatic symptoms is a study limitation, since the BPI was originally developed for the measurement of chronic pain (33), which was an exclusion criterion in the current study. Furthermore, another limitation is that we did not measure the IPQ for the control condition; thus, we cannot determine whether the observed difference between the VR and control conditions could be attributed to differences in the feelings of presence elicited by both conditions.

In a pilot randomized-controlled study examining the potential effects of a novel VR environment on experimentally induced pain using an active control condition, our results showed that the digital immersive tool produced significant immediate effects on pain unpleasantness that did not last at the end of the VR stimulation. With the positive results obtained in the present project, one of the next steps would be to investigate in experimental settings the relative contribution of the digital tool components to the analgesic effects observed, namely the binaural sounds, the nature-based sounds, and/or the visual stimuli of nature scenes. Another avenue would be to test the analgesic effects of the VR treatment in larger samples of participants, especially clinical populations living with chronic pain who also experience significant levels of anxio-depressive symptoms. Finally, considering the fact that our VR environment does not engage higher cognitive functions (e.g., decision-making) like other VR environments that have been used in past studies (e.g., videogames) (73–75), it would be of interest to perform head-to-comparisons of both approaches in order to determine if their analgesic effets and mechanisms of action are comparable or not.