VirtualPain. Preliminary findings from a group-based digital therapeutics intervention for fibromyalgia

Introduction Fibromyalgia (FM) is a disorder characterized by chronic pain, with significant medical, psychological, and socio-economic implications. Although there is limited evidence, cognitive-behavioral therapy (CBT) has shown to be effective in improving FM symptoms. An alternative to enhance CBT effectiveness is to incorporate digital therapeutics (DTx). Aim We conducted a pilot study to investigate whether the addition of a DTx intervention (VirtualPain) to cognitive-behavioral group therapy (CBGT) can reduce pain perception and associated symptoms in patients with FM. Method Ten patients with FM were initially recruited from a public hospital in Barcelona. The treatment consisted of 6 weeks of VirtualPain group sessions and 16 weeks of CBGT. Measures of catastrophizing, self-efficacy, and coping were recorded before, during, and after the protocol. In the DTx sessions, pain intensity was recorded before and after each session. Results The program (DTx and CBGT) showed a significant improvement in pain-related self-efficacy and relaxation measures. Improvement in pain perception was observed only after the DTx intervention. Conclusions This study provides preliminary results regarding the added value of DTx (VirtualPain) as part of a CBGT for FM. The use of the program has facilitated a significant reduction in pain perception in each of the VirtualPain sessions, which provides further evidence of how this technology can be beneficial for improving FM treatments.


Introduction
2][3][4] The prevalence of FM is 2.4% in the general population, more common in adult women (4.2%) than in adult men (0.2%).][7][8][9] The pathophysiological mechanism of FM remains unsatisfactorily understood.A multimodal treatment including pharmacological intervention, 10,11 physical exercise, [12][13][14] and cognitive-behavioral treatment (CBT) is usually offered to patients with FM.][17][18][19][20] CBT can be conducted individually or in a group format (cognitive-behavioral group therapy, CBGT).][23][24][25] Previous studies reported that group interventions for patients with FM achieve significant improvements, but the data remain inconsistent. 25,26igital therapeutics (DTx) are digital tools (e.g., software solutions, or mHealth/eHealth applications) developed to address a medical/psychological conditions.There has been an increase in DTx use in the past years in the field of health, having a three-fold purpose, prevention, management, and/or treatment. 27DTx can complement conventional treatments by improving the quality of life of the individual.2][33][34] DTx brings forward the added value of technology in terms of addressing the psychological treatment in FM.][37][38][39] Our group has developed an affordable and easy-touse 3D laptop version (VirtualPain) 39 to help patients with FM visualize and modify different features of their experience of pain.The current study aims to provide further evidence regarding the efficacy of adding Vir-tualPain as part of CBGT in patients with FM.To address the objective of the study, the first hypothesis was that the program (DTx and CBGT) reduces levels of anxiety and pain perception in patients with FM.The second hypothesis was that the program augments levels of self-efficacy and coping strategies in patients with FM.

Participants
Ten patients were initially recruited from the Moisés Broggi Hospital in Sant Joan Despí (Barcelona).The inclusion criteria were a formal diagnosis of FM made by a specialist in rheumatology, being over the age of 18, and sufficient Spanish proficiency.1][42][43] Exclusion criteria were self-reported epilepsy, 44 visual impairment, and metabolic disorders.Patients with severe mental health disorders (e.g., psychosis, bipolar disorder, major depressive disorder, addictions, etc.) were excluded from the study.

Materials
Pre-and post-treatment measures digital therapeutics and cognitive-behavioral group therapy -Catastrophizing.Catastrophizing cognitions related to pain perception were assessed using the Pain Catastrophizing Scale (PCS), 45,46 which consists of 13 items and has a high internal consistency (α = 0.92). 47-Self-efficacy.The Chronic Pain Self-Efficacy Scale (CPSS), 48,49

Software
VirtualPain consists of a humanoid avatar divided into 27 body regions, 39,42 as shown in Figure 1, Part I.The avatar is displayed in 3D, can be gender-personalized, and allows the user to individually select the most painful parts of their body.The software also has a built-in ecological momentary VAS from 0 (no pain) to 10 (unbearable pain) for each body area to assess pain intensity (Figure 1, Part II).In addition, the software allows pain representation through three features: color gradient, movement speed, and sound volume (Figure 1, parts III and IV).These parameters were implemented in our software based on previous studies reflecting pain experience of different body areas. 35,36,39rdware Given the clinical symptoms of FM, it was decided to run VirtualPain on a semi-immersive three-dimensional (3D) laptop.The system included a hardware (3DStudio) that allowed the creation of a 3D stereoscopic effect, and polarized glasses with circular lenses.The VirtualPain screen was 15.6 inches and the participants stood 60 centimeters from the screen.A computer mouse was used to interact with the environment.In addition, headphones were used to increase immersion in the program.

Procedure
Overview.This study was approved by the Ethics Committee of the University of Barcelona (n.IRB00003099) in collaboration with the Moisés Broggi Hospital in Sant Joan Despí (Barcelona).Patients from the Fibromyalgia Unit of the hospital (N = 50) who met the inclusion criteria were interviewed prior to enrollment; however, 10 patients agreed to participate in this study based on their written informed consent.Introductory meetings with the lead-researcher were conducted with the patients.The meetings consisted of informing the patients about the scope of the study, assessment tools and time points, the group format, and the length of the program.The program consisted of 22 sessions with a weekly frequency and a duration of 90 min/session.The intervention implied six DTx sessions (VirtualPain software), followed by 16 CBGT sessions.
As shown in Figure 2, the assessment time points were pre-intervention assessment session, after six sessions of VirtualPain (mid-assessment), and after 16 CBGT sessions (post-intervention assessment).During VirtualPain, momentary pain levels were assessed before and after the DTx session (Figure 2).Nine participants completed the study.One patient dropped-out of the study due to having an emergency surgery.

The VirtualPain -Cognitive-behavioral group therapy program
VirtualPain -Digital therapeutics group format.The VirtualPain represents an embodiment of the perceived pain on one of the painful body parts.The software is aimed at exposing the patient to their painful body parts with the ultimate goal to reduce pain perception.The procedure of this DTx intervention is summarized in 9 steps (Figure 3), and divided into three phases: (a) pain personification (3-4 minutes), (b) pain quantification (1 minute), and (c) pain exposure (10 minutes).
-Personification: Patients embodied their painful body parts.They chose the (a) color that best represented their pain (step 1) and the (b) color of the absence of pain (step 2) and (c) sound (e.g., forest or beach) (step 3).Patients were asked to select one of the most painful body parts (out of 27 available body parts, which was step 4).Patients were exposed to a single body area per session.In the subsequent sessions, a similar procedure was followed for the same or other painful body areas.-Quantification: Once the pain area had been selected by the patient, a VAS ranging from 0 (no pain) to 10 (unbearable pain) was displayed on the screen to quantify the intensity of pain perceived in that specific area (steps 5 and 6).-Exposure: The software displayed a stereoscopic representation of the body area, colors, and sound chosen to symbolize the pain experience (step 7).Four sliding scales were displayed on the screen as previously selected by the patients in step 6 such as color gradient, speed of movement, volume of sound, and intensity of perceived pain.
The following therapeutic procedure was to encourage the patients to observe their painful body areas and gradually decrease the sliding scales related to the representation of pain.This exercise helped them to recognize and transfer this visual change to their own representation of pain (step 8).The progressive reduction of the pain-related sliding scales and the resulting visual change in the figure was intended to facilitate a modification of the patients' representation of painful body areas.During the session they were encouraged to interact freely with the software to increase their autonomy and self-efficacy.The clinician-scientist only intervened when necessary for the correct functioning of the software.After 10 minutes of interaction, pain levels were assessed with the VAS (step 9).This procedure was repeated for the next five DTx sessions.The clinicianscientist played an increasingly passive role as each patient became more confident in interacting with the DTx software.
Cognitive-behavioral group therapy.The CBGT component of the program was delivered over the next 16 weeks.An experienced clinician-scientist from the hospital was responsible for delivering various CBT techniques commonly used in FM.A comprehensive overview of CBGT can be found in Table 1.

Statistical analysis
A within-subjects design was depicted in this pilot study.Initial descriptive analyses were used to determine socio-demographic and other clinical measures assessed at baseline.
One-way repeated measures ANOVAs were used to determine whether statistically significant differences existed across the intervention (pre-/post-DTx and post-CBGT) in the primary measures (PCS, CPSS, and CPCI-42).Considering the small sample size and data normality assumptions, nonparametric tests were further applied.Wilcoxon signed-rank analyses were performed for the pain levels assessed before and after each DTx session.Friedman tests were performed to explore measurements at the three time points (pre-DTx, post-DTx, and post-CBGT).In the latter analyses, pairwise comparisons were performed with a Bonferroni correction for post-hoc analyses.

Descriptive results
The mean age of our participants was 55.78 years (SD = 10.52,age range: 39 to 71 years), all participants identified themselves as females and reported being  Diet Promote a healthy diet based on nutrients that boost muscle recovery after exercise. 64

13-15
6 Closing session Program review and encouragement of future coping strategies in difficult situations.
married.Other socio-demographic and medical history data of thepatients are shown in Table 2.

Within-DTx intervention outcomes. Pain visual analog scale (VAS).
A Wilcoxon signed-rank test indicated significant reduction across all six VirtualPain sessions (Table 3) as determined by assessment prior and after each DTx sessions (p < .05).
VirtualPain versus CBGT.Catastrophism, self-efficacy, and pain coping strategies.The results obtained before the intervention, after the 6 DTx group sessions, and after 16 CBGT sessions are summarized in Table 4.
Regarding pain coping strategies as assessed by the CPCI scale, Friedman's test analyses showed statistically significant differences at the different assessment times only in the Relaxation subscale (χ 2 (2) =8.706, p = .01).Post-hoc analyses revealed a statistically significant increase in relaxation subscale scores only before and after the DTx intervention (mdn Pre-DTx = 8, mdn PostDTx = 14, p = .029),whereas no statistically significant differences were observed pre-and post-CBGT.

Discussion
This pilot study provides preliminary evidence regarding the added value of DTx in the treatment of FM.Two complementary interventions were proposed as part of a comprehensive psychological treatment for FM, VirtualPain, and CBGT, which consisted of 22 group sessions.The data of this program indicated significant improvements regarding pain perception,  relaxation, and pain management self-efficacy in patients with FM.In addition, VirtualPain intervention was particularly helpful in improving pain perception and relaxation.These changes were maintained during CBGT.
The observed results on the relaxation measure may be explained by the relaxing stimuli included in the software (e.g., the landscape and the sound of the beach).Previous studies showed that exposure to digital nature environments augments relaxation and promotes well-being. 68,69Therefore, VirtualPain may be particularly suitable in facilitating relaxation.This process enhances coping mechanisms for pain and stress management. 70ne of the most prominent hallmarks of this study is the significant reduction in pain perception after each DTx sessions.However, this change was not significant in other variables such as catastrophism, coping, or pain self-efficacy.These results align with a recent systematic review 71 that identified the variable efficacy of psychological therapies in enhancing pain perception in FM.
Although a significant improvement in pain selfefficacy was expected, the VirtualPain intervention showed only a tendency.Nevertheless, a brief intervention with six DTx sessions may not be sufficient for patients to internalize new active coping strategies or to change their negative belief system about pain management. 70egarding CBGT, there was a significant improvement in measures of self-efficacy for pain management (PSE).These findings are consistent with previous research that highlighted the usefulness of CBGT in providing FM patients with information, tools, and resources to improve their active coping with pain. 70In addition, CBGT was delivered over a longer period of time (i.e., 16 weeks), in contrast to the Vir-tualPain intervention, which may facilitate a more profound change in their negative pain beliefs and coping strategies.
Lastly, no significant improvements were observed in other variables such as physical activity, social support, and sleep quality.These results are in line with previous studies showing inconsistent results in the application of CBGT to improve these secondary measures of pain in patients with FM. 25,26,72 DTx represent an added value to support professionals in complementing and enhancing the traditional treatment approaches.Such digital tools are at the beginning of its development in the field of FM, but ongoing research emphasizes the opportunities for additional management and intervention tools. 73,74irtualPain is a new technological device that represents an innovative DTx approach to enable patients with FM to cope with pain more actively.The physical representation of pain is an abstract phenomenon, without shape or tangible characteristics.However, VirtualPain allowed patients to represent pain shape, color, movement, and sound, while accurately localizing it to specific areas of the avatar's body.Since a physical embodiment of pain was available involving multiple sensory inputs (visual and auditory), Virtual-Pain promoted relaxation and a better coping with pain. 75,76VirtualPain has a very intuitive and easy to use interface, which allowed the clinician-scientists to take a more passive and supervisory role during the intervention.This could be a potential advantage when offering VirtualPain to patients remotely (but under supervision) in other non-hospital settings (e.g., at home) as an in-between session support.Considering the high cost of FM treatment in healthcare settings, 77 DTx may be a complementary tool to reduce the cost of psychological interventions. 78VirtualPain may be a suitable adjunct to psychological treatment for FM which does not require costly ongoing health care.This pilot study has important methodological limitations related to the small sample size (i.e., only 9 patients completed the study) and the lack of an active control condition.In the coming years, we expect to conduct a randomized clinical trial with an active control condition to specifically evaluate the influence of VirtualPain in CBGT delivered to patients with FM.Another important limitation is the lack of mid-and long-term follow-up measures to assess long-term improvements.Considering the fact that pain levels measured on VAS returned to their baseline levels after each session, it would also be interesting to increase the number of DTx sessions to assess whether longer exposure will promote the development of active pain coping strategies in patients with FM.VirtualPain will also benefit from increasing body areas and adding further input stimuli (visual, auditory, and haptic).
In conclusion, this study presents preliminary results about the added value of VirtualPain to CBGT.The DTx intervention significantly reduced the perception of pain.The data suggest VirtualPain is an attractive and potentially beneficial complementary intervention to standard treatment for FM.DTx provides an opportunity to reduce the cost of FM treatment of the healthcare system.

Figure 1 .
Figure 1.Software VirtualPain.Note: Sliding scales: color, movement, sound and pain intensity, respectively.Only the first three were used for the present study.

Figure 2 .
Figure 2. Participants' journey through the pilot study.

Table 1 .
Schedule (by sessions) of the applied techniques.

Table 2 .
Quantitative and qualitative sample variables.

Table 3 .
Measurements before and after the administration of the VirtualPain.