36 participants [26 female, 10 male; mean age (SD) = 54.9 (12.8) years] were recruited from the pain center at a large, urban academic medical center by physician referral. Guidelines suggest that 12 participants per group is sufficient for pilot studies, as precision gains for point and variability estimates largely stabilize around this value (35). Thus, a total sample size of 12 was targeted for the control condition and a sample size of 24 was targeted for the experimental arm to ensure a minimum of 12 participants with chronic back pain (CBP) and 12 participants with complex regional pain syndrome (CRPS) were randomized to the VRGI group to ensure that feasibility could be evaluated within each group. Criteria for participant inclusion were (1) English fluency, (2) diagnosis of chronic back pain (CBP) or complex regional pain syndrome (CRPS), (3) average pain intensity of 5 or greater on a 0–10 scale for more than 3 months, and (4) access to a device with video and audio capability along with sufficient Wi-Fi. Criteria for participant exclusion were, per participant's self-report, (1) children and adolescents under the age of 18, (2) history of significant motion sickness, (3) active nausea/vomiting, (4) epilepsy, (5) significant movement problems, and (6) significant vision or hearing impairment.

Interested participants were scheduled for a virtual pre-screening on a phone or video call to assess initial eligibility. Eligible participants then scheduled an appointment through an online video platform (Zoom) where the procedures, requirements, benefits and risks associated with the study were described. Participants provided electronic signed informed consent if they agreed to participate.

After meeting eligibility criteria and providing informed consent, participants were randomized within diagnosis to receive either VR-GI or audio-only GI. Enrollment goal was for 24 participants in the VR-GI group and 12 participants in the audio only group. An additional enrollment goal was to have equal numbers of participants with back pain and CRPS in each group. Participants in the VR-GI group were mailed a VR headset preloaded with the VR-GI program, a tablet, and earbuds. Participants in the audio-only group (AO-GI) were mailed a tablet preloaded with a playlist with GI audio tracks and earbuds.

In a virtual onboarding session with one of the members of the research team, participants completed online baseline assessments of pain intensity, functional outcomes, quality of life, and mood through a REDCap based survey (38). Additionally, participants received basic training in how to complete VR-GI or AO-GI sessions at home using MyCap, a REDCap participant-facing mobile application used to collect patient-reported outcomes (38). All participants were instructed to practice GI at least once per day for 2 weeks. Participants in both groups were instructed to sit in a comfortable position, ideally in a swivel chair for the VR group; standing was discouraged. During onboarding, the “Garden” experience was completed with the research associate and the participant was instructed to complete the “Choose Your Own Adventure” experience the next day. After the first two days, participants were then allowed to complete either experience for the remainder of the 2-week intervention study period. After 2 weeks, participants returned their equipment and completed online post-intervention assessments of pain intensity, pain medication use, functional outcomes, and mood. Those in the VR group were then asked to complete a self-report questionnaire that included questions regarding the comfort, ease of use, overall recommendations, and any adverse effects of the intervention.

Participants were compensated for their participation with Amazon gift cards. Participants were given $10 for attending the onboarding session, $10 for completing the follow-up appointment and $50 for returning the study equipment. Participants could earn a total of $70 for completing all appointments and returning the equipment.

All study procedures were reviewed and approved by the Institutional Review Board (IRB) of the University of Southern California (Study ID: HS 1900549). The study was registered with ClinicalTrials.gov: NCT04849897 Virtual Reality Guided Imagery for Chronic Pain (VRGI).

The VR-GI and AO-GI proprietary programs (BehaVR Inc., dba RealizedCare; Elizabethtown, KY; https://www.realizedcare.com) were designed and developed by psychologists from USC Pain Center in collaboration with Limbix Health Inc. (San Francisco, CA), a for-profit company that was operational during the trial period but is no longer in operation. The VR-GI program was delivered using a consumer grade PICO Goblin VR head-mounted display (PICO Interactive, San Francisco, CA) and offered two computer-generated experiences: The Garden and Choose Your Own Adventure (Figure 1). Each experience had a duration of approximately 15 min, the suggested optimal time for continuous VR use (39). The AO-GI audio tracks had the same narration, without reference to visual elements, and overall duration to the VR-GI experience. The duration of the GI experiences was also consistent with previous studies evaluating AO-GI (3), with brief AO-GI exercises having been observed to be effective in reducing chronic pain in as little as 1–2 min (40).

The Choose Your Own Adventure experience began with participants creating a pain object and, assigning it a visual identity (e.g., shape, color, and texture) to externalize their discomfort. Next, participants had the opportunity to explore 5 different environments with various locations: a castle chamber, a spring meadow, a beach at daylight, a beach at sunset, and a winter landscape. Participants reached these different environments through an elevator accompanied by a guided relaxation exercise, with a focus on progressive muscle relaxation. The experience incorporated structured grounding tasks based on sensory exploration techniques, revolving around sight, sound, and touch to help regulate anxiety and panic symptoms. Participants engaged in interactive activities that encouraged mindfulness and environmental awareness through sight exploration (e.g., uncovering items beneath sand or snow, observing light and atmospheric changes, or mixing magical potions in the castle), sound exploration (e.g., actively listening to environmental sounds such as waves, crackling fire, wind, or a babbling brook), and touch exploration (e.g., using visualization to simulate tactile engagement, such as feeling the texture of seashells, the weight of tree branches, the warmth of fire, or the sensation of lifting clouds from the sky). The narration guided participants through paced breathing exercises and relaxation cues, gradually deepening their engagement with the chosen environment. The interactive elements allowed participants to actively shape their surroundings, reinforcing a sense of control and presence in the moment. The session concluded with a reflection exercise, where participants revisited their “pain object”—a visual representation of their discomfort—and modified its characteristics (e.g., changing its size, shape, or texture) based on how they would like their pain to look and feel. This final step reinforced the idea that pain perception can be modulated through cognitive reframing and sensory engagement.

The Garden experience, where patients engaged in virtual tasks to restore a garden, was designed around sensory immersion and engagement qualities to increase self-efficacy in pain coping and to mitigate pain via gate control mechanisms, which centers on the idea that non-pain related types of stimuli can reduce pain perception. As in the Choose Your Own Adventure experience, participants first created a pain object, assigning it a visual identity (e.g., shape, color, and texture) to externalize their discomfort. However, this object soon caused disruptions within a virtual garden, symbolizing the uncontrolled nature of pain. To restore balance, participants engaged in structured virtual tasks that mimicked mindful actions associated with pain modulation, such as: closing garden gates along their path, reinforcing the idea of controlling pain pathways and reducing its free movement in their environment; Engaging in activities such as repairing a fountain, adding color to faded areas, or trimming overgrown foliage, symbolizing actively restoring balance and control over pain; and selecting natural sounds (e.g., wind in trees, running water) to reinforce attentional redirection away from painful stimuli, a core principle of gate control mechanisms. As with Choose Your Own Adventure, participants were guided by paced breathing exercises and mindfulness cues, helping to cultivate relaxation and cognitive reframing. The experience culminated in a self-reflection phase, where participants revisited their pain object and adjusted its characteristics according to how they would like their pain to look and feel, symbolizing the potential to regulate pain perception and reinforcing a sense of control over their pain to increase self-efficacy.

The mechanisms designed to impact pain perception were consistent between the VR-GI and AO-GI group, as the AO-GI audio tracks had nearly identical narrations to the VR-GI experiences. The only difference between VR-GI and AO-GI experiences was that, whereas participants in VR-GI were able to see, hear, and directly interact with elements of the virtual environment, the AO-GI narration prompted participants to imagine seeing, hearing, and directly interacting with the environments in the same way.

We first present basic demographic characteristics of the study sample followed by descriptive and qualitative results related to feasibility, acceptability, and patient experience. For the self-report questionnaire, means and standard deviations of responses on the Likert scale questions were calculated as well as a count of participants' preference between the two VRGI experiences. A grounded theory approach was used to analyze free response answers on the self-report questionnaire to derive emergent themes (49). Themes were generated through an inductive process of coding involving iteratively categorizing and sorting data through pattern recognition (50, 51). Notes were reviewed, iteratively coded, and grouped into themes until consensus on key themes was reached among study authors. Sample quotes by participants are included for illustrative purposes. For the preliminary efficacy testing, we present the means, standard deviations, and the percent difference between baseline and post-intervention within each of the two groups for each of the constructs. Given that the primary focus of the present study was evaluating feasibility, the study was not powered for significance testing, and thus between-group and within-group significance testing was not conducted.

Participant demographics are presented in Table 1.

96 participants were screened for eligibility. 15 (15.6%) did not meet enrollment criteria (pain less than 5/10 or neck pain/ neck movement problems), 15 (15.6%) declined to participate, and 30 (31.3%) were unable to participate for other reasons, including failure to schedule a consent session and family circumstances. Ultimately, 36 participants (n = 24 randomized to the VR-GI group and n = 12 randomized to the AO-GI group) were enrolled in the study resulting in a 44.4% uptake rate (36 out of 81 eligible participants). Study tolerability, as measured by trial completion rate, was 88.9% (32 out of 36 participants), with one participant in the VR-GI group discontinuing the intervention due to difficulty using the VR headset and three participants (2 VR-GI group, 1 AO-GI group) lost to follow-up.

Of the 21 participants in the VR-GI group who completed the study, the adherence rate was 66.4%. The average number of completed VR sessions was 9.3 over the 14-day intervention period.

Means and standard deviations for all Likert scale questions on the self-report questionnaire are reported in Table 2.

Table 3 shows the baseline and post-intervention means and standard deviations for each outcome by group.

From baseline to post-intervention, pain ratings for the VR-GI group all showed a greater numerical decrease in pain (NRS) compared to pain ratings for the AO-GI group. The VR-GI lowest pain score decreased by 8.74% (baseline lowest pain score = 4.0, post-intervention lowest pain score = 3.71), whereas the AO-GI lowest pain score decreased by 5.91% (baseline lowest pain score = 3.92, post-intervention lowest pain score = 3.64). The VR-GI group highest pain score decreased 6.96% (baseline highest pain score = 8.42, post-intervention highest pain score = 7.86) compared to a 1.18% increase in the AO-GI group (baseline highest pain score = 7.75, post-intervention highest pain score = 7.4). The VR-GI group average pain score decreased 8.22% (baseline average pain score = 6.96, post-intervention average pain score = 6.08) compared to a 2.52% decrease in the AO-GI group (baseline average pain score = 5.75, post-intervention average pain score =  5.45).

From baseline to post-intervention, the VR-GI group showed a greater numerical decrease in anxiety compared to the AO-GI group. The within-group reduction in anxiety was 43.9% (baseline GAD-2 score = 1.83, post-intervention GAD-2 score = 1.0) in the VR-GI group. In the AO-GI group, the reduction was 22.3% (baseline GAD-2 score = 1.58, post-intervention GAD-2 score = 1.2).

The VR-GI group also showed a greater numerical decrease in depression compared to the AO-GI group from baseline to post-intervention. The within-group reduction in depression was 52.3% (baseline PHQ-2 score = 2.0, post-intervention PHQ-2 score = 0.86) in the VR-GI group. In the AO-GI group, the reduction was 5% (baseline PHQ-2 score = 1.33, post-intervention PHQ-2 score = 1.30).

From baseline to post-intervention for the SF-12 Mental Component score, the VR-GI group showed a greater numerical improvement in mental health compared to the AO-GI group. The within-group increase in mental health was 21.6% (baseline mental health score = 43.61, post-intervention mental health score = 50.43) in the VR-GI group. In the AO-GI group, the increase was 13% (baseline mental health score = 43.45, post-intervention mental health score = 48.55).

From baseline to post-intervention for the SF-12 Physical Component score, the VR-GI group showed a 3% increase in physical health (baseline physical health score = 27.02, post-intervention physical health score = 27.93). The AO-GI group showed a 5% decrease in physical health (baseline physical health score = 29.06, post-intervention physical health score = 27.74).

Retention and study uptake rates, respectively 88.9% and 44.4%, were relatively high (28, 52, 54). Recruitment through physician referrals are a possible factor driving high uptake rates. At-home interventions coupled with video calls allowed for greater flexibility during the trial, which may have contributed to high recruitment and retention. Additionally, assessments were conducted solely online with assessment reminders from research coordinators, which could have contributed to the high retention rate.

Study adherence at 66.4% when looking at VR headset data (completion of at least one 15-min session per day) was also notably high in comparison to previous at-home VR studies, which have had low and highly variable adherence, with a meta-analysis study on VR for pain treatment defining strong adherence to be 64% (52, 53). High study adherence could have also been influenced by reminders from research coordinators as well as the low recommended frequency and duration of intervention, which was daily and at least for 15 min. Future studies could be conducted over longer trial periods with less participant support from research coordinators to further assess overall adherence in a more naturalistic context.

In terms of acceptability, participant feedback was mixed. VR-GI had expected side effects of dizziness and nausea; these are well-known and common side effects to VR (55). These adverse effects, in addition to feedback around the weight of the headset and the impact of the headset and VR-GI experiences in triggering pain, could have contributed to the moderately low ratings of comfortability in participant feedback. This feedback may have been driven by participants who had chronic neck or hand pain who reported discomfort with the amount of movement that the VR experiences required. Though there was noted discomfort associated with VR-GI, high ratings of ease of integration and use of the VR hardware, do support the acceptability of the intervention. It is important to note that the average age of participants was 56.4 years and most reported having never previously experienced VR, thus the relatively high ratings for ease of use and ability to fit VR-GI into a daily routine are encouraging. Future studies should consider excluding individuals with neck or hand pain and/or consider using a handheld remote or lighter headset. Participant feedback around changes to the content of the VR-GI experiences to reduce pain triggering content can also be incorporated into subsequent versions of the VR-GI experiences.

Feedback around participant experience was largely positive. Though participants reported that VR-GI did not specifically reduce their pain, VR was rated as a helpful coping mechanism in managing their pain. Patients reported that they would be likely to recommend VR-GI to a friend and they wished to continue using it.

Though the study's small sample size limits conclusions around efficacy, average and highest pain scores showed numerically greater reductions in the VR-GI group compared to the AO-GI group. However, these effects were well below a clinical significance threshold. On the other hand, mental health outcomes as measured by the GAD-2, PHQ-2, and SF-12 mental health subscale all demonstrated numerical improvements in mental health outcomes that met clinical significance thresholds. Participant qualitative feedback also supported improvements around mental health. This preliminary evidence points to a potential impact of VR-GI in particular on mental health outcomes, in line with theoretical perspectives that VR-GI reduces pain via top-down modulation of pain pathways by cognitive and emotional brain regions. Future research is necessary to examine the efficacy and clinical significance of VR-GI to improve chronic pain and mental health outcomes via a larger, statistically powered clinical trial, to assess potential for long-term efficacy and symptom remission with longer term follow-up timepoints, and to further explore the mechanisms by which VR may impact chronic pain.

Although recruitment was aimed at participants with back pain and CRPS, neck pain was not specifically listed as an exclusion criterion and may have contributed to complications in using VR for participants who also had neck pain.

Future iterations of the VR headset can improve the logging system to more accurately monitor engagement metrics. Additionally, VR as a delivery method for pain management has logistical barriers such as discomfort from weight of hardware and equipment and lack of accessibility due to price.