A single-blind, randomized experimental clinical trial was conducted among women diagnosed with FM recruited through the Association of Fibromyalgia, “AFINSFACRO,” in Móstoles, Spain. Following the selection of patients who met the inclusion criteria and the collection of informed consent forms and information sheets, according to ethical standards, the patients were randomly assigned to 1 of the 3 groups. The first group performed 20 minutes of exercise plus 10 minutes of VR (G1), the second group performed 30 minutes of exercise (G2), and the control group (CG) did not perform any exercise or VR treatment.

This study was registered at ClinicalTrials.gov (NCT05933941) and approved by the Clinical Research Committee of the Hospital Clínico San Carlos (Madrid, Spain; ID: VRTCNPPFM-13/07/2023). The research was conducted from April 1, 2024, to January 30, 2025. All participants gave informed consent, and the general scope of this study was explained to them via a participant information sheet. This clinical trial was designed and reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) guidelines, with specific adherence to the CONSORT-Harms (Consolidated Standards of Reporting Trials Harms Extension) 2022 statement (Checklist 1) to ensure transparent and comprehensive reporting of adverse events and safety outcomes.

The QuestionPro survey software (QuestionPro, Inc) was used to calculate the required sample size, considering a 95% CI and a 5% α error. The sample size calculation was based on the study by Gulsen et al [8]. A total of 56 women were enrolled, of whom 2 withdrew for personal reasons unrelated to the study. The inclusion criteria comprised female patients aged 20 to 65 years with a confirmed diagnosis of FM and chronic cervical pain lasting more than 3 months. The exclusion criteria included vertigo, claustrophobia, epilepsy, pregnancy, or refusal to provide informed consent.

A consecutive, nonprobabilistic convenience sampling strategy was applied to participants who met the inclusion criteria.

Sociodemographic variables included age, height, weight, BMI, marital status, pain medication use, employment status, smoking history, and comorbid conditions such as restless legs syndrome, chronic fatigue syndrome, temporomandibular joint dysfunction, migraines, irritable bowel syndrome, multiple chemical sensitivity, anxiety, and depression. All these sociodemographic variables were collected using a self-administered survey.

The following tools were used in this study:

The intervention was conducted over a period of 1 month. G1 and G2 participated in 2 sessions per week. G1 performed 20 minutes of cervical mobility and strengthening exercises (Multimedia Appendix 1), followed by 10 minutes of immersive VR therapy. G2 completed 30 minutes of cervical mobility and strengthening exercises. The CG did not perform any cervical mobility or strengthening exercises nor participate in immersive VR therapy. The immersive VR therapy was delivered using Meta Quest 2000 headsets, using the game “Interkosmos 2000.” In the game, participants assumed the role of a spacecraft pilot navigating through a series of rings while avoiding meteoroids by performing neck movements according to the game’s instructions. The difficulty level was adjusted as follows: the first 3 sessions were carried out in “easy” mode, allowing a maximum cervical mobility of 30°. The subsequent 3 sessions were conducted in “medium” mode, allowing up to 60° of cervical mobility. The final 2 sessions were performed in “hard” mode, which not only increased the spacecraft’s speed but also enabled a full cervical range of motion. All groups underwent assessments of cervical ROM including flexion, extension, right and left lateral inclination, and right and left rotation. In addition, pain intensity in the upper trapezius (bilaterally) and in the right and left occipital regions was quantified using an algometer. Evaluations were conducted at 4 time points: baseline (preintervention), immediately after the intervention, 15 days postintervention, and 1 month postintervention. All follow-up assessments were performed at the association’s premises. After each session, participants from G1 and G2 reported their perceived levels of cervical pain and fatigue. All outcome measures were collected by a research assistant blinded to the study objectives and group allocations.

Evaluations were conducted at 4 time points: baseline (preintervention), immediately postintervention, 15 days postintervention, and 1-month postintervention. All follow-up assessments were conducted at the association’s headquarters. After each session, participants in G1 and G2 reported perceived levels of cervical pain and fatigue.

All outcome measures were collected by a research assistant who was blinded to both the study’s objectives and the participants’ group assignments.

Statistical analyses were performed using SPSS 29.0 (IBM Corp). The normality of quantitative variables was assessed with the Kolmogorov-Smirnov test. Depending on distribution, data were described using means and SDs or medians, IQRs, and ranges. Qualitative variables were expressed as percentages and absolute values. Baseline comparisons between the groups were conducted using chi-squared tests or ANOVA with Bonferroni post hoc analysis. Temporal changes in outcomes were analyzed with paired tests, and intergroup differences were analyzed using ANOVA, Bonferroni post hoc, or Kruskal-Wallis tests, as appropriate. Correlations between quantitative variables were assessed using the Pearson or Spearman tests, and associations between qualitative variables were assessed using chi-squared tests. Statistical significance was set at P<.05.

This study received approval from the institutional review board of Hospital Clínico San Carlos (23‐458 EC) and was conducted in accordance with the Spanish legislation, including Law 41/2002 on patient autonomy and Organic Law 3/2018 on data protection and digital rights. These laws prohibit the processing of sensitive personal data such as racial or ethnic origin, political or religious beliefs, biometric identifiers, health information, and sexual orientation. The study also adhered to the ethical principles outlined in the World Medical Association’s Declaration of Helsinki 2014 [50]. All procedures conducted in this study complied with applicable ethical standards. Informed consent was obtained from all participants prior to their inclusion in the study. Participant privacy and confidentiality were strictly protected, and all data were handled and stored in accordance with relevant data protection regulations. No personally identifiable information was collected or disclosed. Participants did not receive any financial or material compensation for their participation.

The final sample included 54 women with a mean age of 54.26 (SD 7.7) years. Participants were distributed among the groups by computer-generated random number sequence (Figure 1).

Among the participants, 33 (61%) presented chronic fatigue syndrome, 37 (68%) had temporomandibular joint dysfunction, and 16 (33%) reported restless legs syndrome. Regarding the psychological comorbidities, 33 (61%) participants presented anxiety and 13 (24%) depression. Baseline comparisons revealed no statistically significant differences among groups in age, BMI, or other demographic variables. However, subjective measures showed group-level differences in several baseline scales, including FIQ, EQ-5D, CSI, NDI, and Borg scale. Almost all variables at baseline start from similar values, although G1 has a value of 1 point lower on the VAS scale, indicating that they have less pain at the outset. However, in variables such as algometry, the averages reflect similar values compared to the other 2 groups (Multimedia Appendix 2).

Table 1 shows the differences in the mean values measured before therapy and immediately after its end. We found significant differences in all groups that received intervention in FIQ, CSI, NDI, right and left trapezius, occipital algometer, and in all movements in which ROM was evaluated. For the right and left trapezius and occipital muscles, algometric measurements were obtained, and ROM was assessed across all evaluated movements. About the treatment adherence variable, G1 obtained an average of 94 points out of 100, compared to G2, whose post-treatment average was 74.72. The summary of the comparison between baseline measures and measures immediately after intervention (intragroup comparisons). Shown are the differences in the mean values between both time points (Multimedia Appendix 3).

Summary of the comparison between baseline and 1-month post-intervention scores for FIQ, EQ-5D, TSK, CSI, and NDI (intragroup comparisons). Shown are the differences in the mean values between both time points (Table 2). The differences in the measurement times of the other variables can be observed in Multimedia Appendix 4.

After confirming the effect of both interventions, we compared the intervention groups to see whether VR had a significant influence on the effect of the therapy. Table 3 shows that the ANOVA between groups was significant for FIQ, CSI, and NDI at both postintervention and 1-month follow-up (P<.001). Immediately after treatment, both intervention groups (G1 and G2) improved significantly compared with the CG, with no differences between G1 and G2. At 1 month, G1 maintained superior outcomes across all measures, showing significantly better scores than both GC and G2 (P<.001), while G2 no longer differed from GC for FIQ and CSI. For NDI, all pairwise comparisons were significant (P<.001), confirming that both interventions reduce neck disability, with the VR-enhanced program providing the greatest and most sustained benefit.

This study evaluated the effectiveness of VR as an adjunctive therapy for cervical pain in women with FM. The main findings revealed that combining VR with mobility and strengthening exercises produced significant improvements in pain perception, ROM, and functional performance compared with physical therapy alone. These benefits were also sustained at 1-month follow-up, emphasizing the potential of immersive VR interventions to enhance therapeutic outcomes in individuals with FM.

In the intergroup analysis, the G1 consistently outperformed both G2 and CG in those outcomes most closely related to global disease impact and NDI. Specifically, G1 showed significantly greater and more sustained improvements in FIQ and CSI scores than both CG and G2, whereas improvements in G2 tended to converge toward control values at 1-month follow-up. Similarly, NDI scores decreased in both intervention groups immediately after treatment, but at follow-up, a clear gradient GC>G2>G1 was observed, indicating the largest and most persistent reduction in neck-related disability in the combined intervention. These effects were paralleled by a recurrent pattern of superior gains in cervical ROM and higher-pressure pain thresholds in the trapezius and occipital in G1, while the Time Up Go test improved in both intervention groups compared with CG and TSK decreased more markedly in G1 at 1 month. By contrast, the VAS and Borg scale showed only limited discrimination between the groups, suggesting that the added value of VR was more evident in multidimensional impact and sensitization-related and functional domains than in isolated pain ratings.

This intergroup pattern is consistent with previous evidence in FM and chronic neck pain, indicating that VR, particularly when used as an adjunct to active exercise, preferentially enhances global impact, disability, and pain-modulation outcomes. In patients with FM, a study reported that fully immersive VR combined with aerobic and pilates training produced greater improvements in pain, kinesiophobia, fatigue, physical activity levels, and mental quality of life than exercise alone, while both groups improved in FM impact, supporting an adjunctive role of immersive VR in comprehensive rehabilitation programs [8]. Other studies showed that, in individuals with chronic neck pain, VR-based cervical training led to larger gains in pressure pain thresholds at the upper cervical levels and greater reductions in functional limitation compared with motor control exercises, despite the absence of between-group differences in pain intensity and quality of life, which parallels our finding of more robust intergroup differences in pressure pain thresholds, ROM, and disability than in VAS score [51]. Furthermore, a randomized crossover trial in women with FM found that VR increased cold pain thresholds and tolerance in both FM patients and pain-free controls, whereas effects on pain intensity were limited, reinforcing the notion that VR may primarily modulate pain processing rather than consistently decreasing reported pain intensity [52]. Taken together, these converging results suggest that combining immersive VR with targeted cervical exercise may primarily potentiate mechanisms related to central sensitization, motor control, and the global impact of FM rather than merely amplifying short-term analgesic effects.

VR has emerged as a promising nonpharmacological intervention for the symptom management of FM. Its immersive and interactive features provide cognitive distraction, emotional engagement, and motor stimulation, which together enhance adherence and reduce pain intensity. Previous studies have demonstrated that VR can improve mood, motivation, and functional capacity when applied alongside traditional rehabilitation or psychological therapies. This approach not only benefits patients with FM but may also be applicable to other chronic pain conditions [49,50,53].

The use of VR has been demonstrated to significantly influence pain relief, motor function, and joint mobility among patients with a range of chronic pathologies [53]. The primary applications of VR in health care include the management of pain and anxiety as well as the enhancement of patient motivation [47,54,55].

While it is not possible to make direct comparisons between this study and research conducted by other authors, the described implementation of an 8-session intervention resulted in statistically significant outcomes for the variables under investigation. This suggests VR is effective when combined with active exercise therapy.

The comparative analysis concerning VR and physical exercise indicated that there was minimal divergence in the measured variables. In a separate study [56], 44 patients underwent an intervention for 4 weeks, with 2 sessions per week. The intervention was divided into 2 groups: G1 (whose members performed only cervical mobility exercises) and G2 (whose members conducted a treatment based solely on VR exercises). The findings indicated that there were no statistically significant differences between the 2 groups across the different variables, including pain, ROM, neck disability, incapacitating pain, and anxiety. However, in this study, the combination of VR with cervical mobility exercises yielded a significantly better outcome. Furthermore, these improvements were maintained over time (1 month) to a greater degree in the group subjected to both therapies combined when compared to the group that performed only mobility exercises. It is important to highlight that the study with which this investigation was compared implemented its intervention in a population without FM. Consequently, the observed discrepancy in outcomes could be due to this factor. A similar study was conducted [51], with an equivalent number of sessions implemented. The outcomes observed in this research were analogous to those obtained in our research, as the investigators combined active therapy and VR exercises for patients with FM [55]. However, the FM cohort in that report comprised only 20 patients. In addition, the active component focused on aerobic training and Pilates instead of the cervical exercises used in our research.

Another study assessed the efficacy of VR for patients with chronic neck pain versus a CG that performed motor control exercises. In this case, the study spanned a period of 6 weeks, comprising 3 weekly sessions. Their findings revealed that the utilization of VR was advantageous when measuring pain due to pressure with an algometer at C1-C2 and C5-C6, and it was also beneficial when considering functional limitations. However, no significant differences were observed between the groups with respect to pain intensity, muscle performance, or quality of life (36-Item Short Form Health Survey). It is evident that the results of this study deviate from those previously observed. However, it should be noted that the mentioned study did not include the population with FM, and no group underwent combined VR and active therapy [51].

Following a thorough review of the scientific literature, we found no studies addressing the use of VR in the cervical region using this protocol. Other studies have applied VR in FM use, games, and global exercises, focusing on observing aspects such as anaerobic capacity, balance, or fatigue [7,54,55]. In this study, the focus was pain in the cervical region and other more global variables such as fatigue, VAS, and FIQ. Therefore, our study offers a novel contribution to this field of research by addressing this gap in the existing literature. Given that patients with FM experience cervical pain, headaches, and tender points in the occipital regions, it is imperative to reduce the associated symptoms.

The limitations of this study lie in the fact that the results are not representative of a heterogeneous population with FM, since the cohort of participants in this research consisted solely of women. Due to the challenging nature of the disease, it was not possible to consider medication used by participants, which may have influenced the results. Finally, the study did not include a group that used only VR, so we cannot conclude that the results are attributable to the VR component or its combination with exercise.

This approach not only benefits patients with FM but may also be applicable to other chronic pain conditions [49,50,53].

Virtual reality, when added to cervical mobility and strengthening exercises, produced greater and more sustained improvements in disease impact, neck disability, central sensitization, kinesiophobia, and functional outcomes in women with FM than exercise alone or no intervention. The improvements were maintained for 1 month in the G1 group in the variables evaluated. These findings support VR as an effective adjunct to active therapy, with potential benefits for symptom reduction and warrant further research on long-term effects, cost-effectiveness, and applicability to broader chronic pain populations.