The sham VR control is a non-immersive set of 56 daily virtual experiences, tuned to the length of the RelieVRx.

Change in sleep was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 6a. This form consists of 6 items which asked participants to assess quality and attributes of their sleep patterns over the prior 7 days. Response options for the sleep quality item range from "Very poor" = 1 to "Very good = 5" and from "Not at all" = 1 to "Very much" = 5 for the remaining five items. The two positively phrased items are reverse-coded and sum scores are calculated and the raw sum score is rescaled on the PROMIS conversion table to determine a standardized T-score (overall mean of 50 and standard deviation of 10). For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with greater sleep disturbance and decreased overall sleep quality relative to baseline and negative mean scores were associated with decreased sleep disturbance and increased overall sleep quality relative to baseline.

Change in cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS 29) Cognitive Function domain form. This form consists of 2 questions which asked participants to assess cognitive function over the prior 7 days. Both questions for this measure are summed up on a 5-point Likert scale ranging from "Not at all" to "Very much" = 4, for an overall possible scoring range of 0-8 such that higher scores are associated with increased overall cognitive function. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with increased overall cognitive function from baseline and negative mean scores were associated with decreased overall cognitive function from baseline. Scores were summarized by study arm using basic descriptive statistics.

Change in social function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Social 4a Heal form. This form consists of 4 items which asked participants to assess their leisure, family, work and general social function behaviors over the prior 7 days. Responses to the 4 items are summed up on a 5-point Likert scale ranging from "Never" = 0 to "Always" = 4, for an overall possible scoring range of 0-16 such that higher scores are associated with increased inhibition in social function/participation. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with decreased inhibition to social participation relative to baseline and negative mean scores were associated with increased inhibition to social participation relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

Change in physical function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Social 6b Heal form. This form consists of 6 items which asked participants to assess their physical function and ability to conduct chores, climb stairs, walk, and run errands. Responses to the 6 items are summed up on a 5-point Likert scale ranging from "Without any difficulty" (or "Not at all") = 0 to "Unable to do" (or "Cannot do") = 4, for an overall possible scoring range of 0-24 such that higher scores are associated with increased inhibition in physical function. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with decreased inhibition in physical function relative to baseline and negative mean scores were associated with increased inhibition in physical function relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

Change in depression was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression 4a Heal form. This form consists of 4 items which asked participants to assess the frequency of depressive symptoms over the prior 7 days. Responses to the 4 items are summed up on a 5-point Likert scale ranging from "Never" = 0 to "Always" = 4, for an overall possible scoring range of 0-16 such that higher scores are associated with a greater level of depression-related symptoms. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with greater frequency of depression-related symptoms relative to baseline and negative mean scores were associated with reduced frequency of depression-related symptoms relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

Change in anxiety was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4a Heal form. This form consists of 4 items which asked participants to assess the frequency of onset of anxiety-related symptoms over the prior 7 days. Responses to the 4 items are summed up on a 5-point Likert scale ranging from "Never" = 0 to "Always" = 4, for an overall possible scoring range of 0-16 such that higher scores are associated with a greater level of anxiety-related symptoms. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with greater frequency of anxiety symptoms relative to baseline and negative mean scores were associated with reduced frequency of anxiety symptoms relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

The investigators will collect saliva the morning of each time frame and test for cortisol, which is a chronic pain inflammatory biomarker. Higher levels of salivary cortisol may indicate greater chronic pain symptoms.

The investigators will collect blood and urine samples at each time frame and test for serum cortisol, which is a chronic pain inflammatory biomarker. Higher levels of serum cortisol may indicate greater chronic pain symptoms.

The investigators will collect blood samples at each time frame and test for serum c-reactive protein, which is a chronic pain inflammatory biomarker. Higher levels of serum c-reactive protein may indicate greater chronic pain symptoms.

The investigators will collect blood samples at each time frame and test for serum cytokines, which is a chronic pain inflammatory biomarker. Higher levels of serum c-reactive protein may indicate greater chronic pain symptoms.

The sham virtual reality (VR) device is also by RelieVRx. However, it lacks the immersive nature of the interventional VR. Control participants will complete 20-30 minute VR sessions twice per week over the course of 6 weeks.

Sham VR: The sham VR control is a non-immersive set of 56 daily virtual experiences, tuned to the length of the RelieVRx.

Total of all reporting groups

The number of participants who did not complete High School (HS), completed their General Educational Development (GED) or equivalent, received their HS diploma, or completed 1 or more years of college/university were summarized by study arm.

Pain, Enjoyment of Life, and General Activity (PEG) scale scores were obtained at baseline. The PEG score is a 3-item pain assessment tool that measures the impact of pain intensity and interference on a participant's daily life. The PEG score is calculated by averaging the responses to three questions each on a scale of 0-10. Higher average (mean) scores are associated with increased impact of pain on a participant's life. Scores were summarized by study arm using basic descriptive statistics.

The sham virtual reality (VR) device is also by RelieVRx. However, it lacks the immersive nature of the interventional VR. Control participants will complete 20-30 minute VR sessions twice per week over the course of 6 weeks.

Sham VR: The sham VR control is a non-immersive set of 56 daily virtual experiences, tuned to the length of the RelieVRx.

Change in Opioid Craving was assessed using the Opioid Medication Craving Visual Analog Scale. This 3-item scale asked participants to rate how strong their desire to use opioids was during the previous 24 hours; the likelihood that they would use opioids if placed in the environment in which they had previously used drugs/alcohol; and how strong their urges for opioids are when something in their environment reminds them of it. Responses were marked on visual scale ranging from 0-100 where "0" signified 'No Desire or Likelihood of Use' and "100" signified 'Strong Desire or Likelihood of use. Positive mean scores were associated with increased opioid craving from baseline and negative mean scores were associated with decreased opioid craving from baseline. Scores were summarized by study arm using basic descriptive statistics.

8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

The percentage of participants contacted who were enrolled into the study was used to assess the feasibility of the study. Results were summarized using basic descriptive statistics.

All participants who were contacted enrolled into the study.

Change in pain interference was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Short Form 4a scale. This form consists of 4 items which asked participants to rate the degree to which their pain interfered with a range of activities over the prior 7 days. Responses to the 4 items are summed up on a 5-point Likert scale ranging from "Not at all" = 0 to "Very much" = 4, for an overall possible scoring range of 0-16 such that higher scores are associated with greater pain interference. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with greater pain interference relative to baseline and negative mean scores were associated with reduced pain interference relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

3-week Pain Interference (PROMIS, Pain Interference 4a) data was not collected and, therefore, results were not available to be reported. 8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

Change in sleep was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 6a. This form consists of 6 items which asked participants to assess quality and attributes of their sleep patterns over the prior 7 days. Response options for the sleep quality item range from "Very poor" = 1 to "Very good = 5" and from "Not at all" = 1 to "Very much" = 5 for the remaining five items. The two positively phrased items are reverse-coded and sum scores are calculated and the raw sum score is rescaled on the PROMIS conversion table to determine a standardized T-score (overall mean of 50 and standard deviation of 10). For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with greater sleep disturbance and decreased overall sleep quality relative to baseline and negative mean scores were associated with decreased sleep disturbance and increased overall sleep quality relative to baseline.

3-week Sleep (PROMIS, Sleep Disturbance 6a) data was not collected and, therefore, results were not available to be reported. 8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

Change in cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS 29) Cognitive Function domain form. This form consists of 2 questions which asked participants to assess cognitive function over the prior 7 days. Both questions for this measure are summed up on a 5-point Likert scale ranging from "Not at all" to "Very much" = 4, for an overall possible scoring range of 0-8 such that higher scores are associated with increased overall cognitive function. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with increased overall cognitive function from baseline and negative mean scores were associated with decreased overall cognitive function from baseline. Scores were summarized by study arm using basic descriptive statistics.

3-week Cognitive Function (PROMIS 29 Cognitive Function) data was not collected and, therefore, results were not available to be reported. 8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

Change in social function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Social 4a Heal form. This form consists of 4 items which asked participants to assess their leisure, family, work and general social function behaviors over the prior 7 days. Responses to the 4 items are summed up on a 5-point Likert scale ranging from "Never" = 0 to "Always" = 4, for an overall possible scoring range of 0-16 such that higher scores are associated with increased inhibition in social function/participation. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with decreased inhibition to social participation relative to baseline and negative mean scores were associated with increased inhibition to social participation relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

3-week Social Function (PROMIS, Social 4a Heal) data was not collected and, therefore, results were not available to be reported. 8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

Change in physical function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Social 6b Heal form. This form consists of 6 items which asked participants to assess their physical function and ability to conduct chores, climb stairs, walk, and run errands. Responses to the 6 items are summed up on a 5-point Likert scale ranging from "Without any difficulty" (or "Not at all") = 0 to "Unable to do" (or "Cannot do") = 4, for an overall possible scoring range of 0-24 such that higher scores are associated with increased inhibition in physical function. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with decreased inhibition in physical function relative to baseline and negative mean scores were associated with increased inhibition in physical function relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

3-week Physical Function (PROMIS, Social 6b Heal) data was not collected and, therefore, results were not available to be reported. 8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

Change in depression was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression 4a Heal form. This form consists of 4 items which asked participants to assess the frequency of depressive symptoms over the prior 7 days. Responses to the 4 items are summed up on a 5-point Likert scale ranging from "Never" = 0 to "Always" = 4, for an overall possible scoring range of 0-16 such that higher scores are associated with a greater level of depression-related symptoms. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with greater frequency of depression-related symptoms relative to baseline and negative mean scores were associated with reduced frequency of depression-related symptoms relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

3-week Depression (PROMIS, Depression 4a Heal) data was not collected and, therefore, results were not available to be reported. 8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

Change in anxiety was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4a Heal form. This form consists of 4 items which asked participants to assess the frequency of onset of anxiety-related symptoms over the prior 7 days. Responses to the 4 items are summed up on a 5-point Likert scale ranging from "Never" = 0 to "Always" = 4, for an overall possible scoring range of 0-16 such that higher scores are associated with a greater level of anxiety-related symptoms. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with greater frequency of anxiety symptoms relative to baseline and negative mean scores were associated with reduced frequency of anxiety symptoms relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

3-week Anxiety (PROMIS, Anxiety 4a Heal) data was not collected and, therefore, results were not available to be reported. 8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

Change in stress was assessed using the National Institutes of Health (NIH) Perceived Stress Scale (PSS-10) which consists of 10 items asking participants to assess the frequency of onset of stress-related symptoms over the prior month on a 5-item Likert scale ranging from 0-4. Six of the ten items are coded such that "Never" = 0 and "Very often" = 4; and four of the ten items are reverse-coded such that "Never" =4 and "Very often" = 0, for an overall scoring range of 0-40. The higher the score the worse the perceived stress. For purposes of reporting of this change from baseline outcome measure, positive mean scores were associated with greater frequency of stress relative to baseline and negative mean scores were associated with reduced frequency of stress relative to baseline. Scores were summarized by study arm using basic descriptive statistics.

3-week Stress (NIH Perceived Stress Scale) data was not collected and, therefore, results were not available to be reported. 8 participants in the RelieVRx arm and 6 participants in the Sham Virtual Reality arm completed the study.

The investigators will collect saliva the morning of each time frame and test for cortisol, which is a chronic pain inflammatory biomarker. Higher levels of salivary cortisol may indicate greater chronic pain symptoms.

The investigators will collect blood and urine samples at each time frame and test for serum cortisol, which is a chronic pain inflammatory biomarker. Higher levels of serum cortisol may indicate greater chronic pain symptoms.

The investigators will collect blood samples at each time frame and test for serum c-reactive protein, which is a chronic pain inflammatory biomarker. Higher levels of serum c-reactive protein may indicate greater chronic pain symptoms.

The investigators will collect blood samples at each time frame and test for serum cytokines, which is a chronic pain inflammatory biomarker. Higher levels of serum c-reactive protein may indicate greater chronic pain symptoms.

The sham virtual reality (VR) device is also by RelieVRx. However, it lacks the immersive nature of the interventional VR. Control participants will complete 20-30 minute VR sessions twice per week over the course of 6 weeks.

Sham VR: The sham VR control is a non-immersive set of 56 daily virtual experiences, tuned to the length of the RelieVRx.