Introduction

Zoster-associated pain (ZAP) is a complication caused by nerve damage resulting from the reactivation of the varicella-zoster virus (VZV).1 Clinically, ZAP is categorized into three temporal stages: the acute phase, occurring within 1 month of rash onset; the subacute phase, extending from 1 to 3 months after rash resolution; and the chronic phase, in which pain persists for more than 3 months, commonly referred to as postherpetic neuralgia (PHN).2,3 As one of the most prevalent neuropathic pain conditions,4 ZAP is characterized by spontaneous, persistent, or paroxysmal severe pain in the affected dermatome, typically described as burning, electric shock like, or pricking sensations, often accompanied by hyperalgesia or sensory disturbances.5,6 Following primary infection, VZV establishes lifelong latency in sensory ganglia. When host immunity declines, the virus reactivates, replicates, and spreads along sensory nerve fibers to the skin, directly inducing nerve inflammation and structural damage.7 Epidemiological evidence indicates that 30–50% of patients with herpes zoster develop PHN, with the incidence increasing markedly with advancing age.8 The chronic pain associated with ZAP frequently leads to sleep disturbances, psychological distress, and motor dysfunction, often exacerbating the clinical burden through complex interactions with negative emotional states.9,10 Given the continuum of this condition and the accelerating aging of the global population, effective interventions that address the full disease spectrum are urgently needed.11

Pulsed radiofrequency (PRF) neuromodulation of the dorsal root ganglion is a key interventional strategy for ZAP. CT-guided PRF has demonstrated efficacy in reducing pain intensity and preventing the progression to PHN.12,13 Nevertheless, a subset of patients continue to experience residual local pain following treatment, which may impede functional recovery and diminish treatment satisfaction.14 Given the rising incidence of PHN, optimizing ZAP management—particularly through integrated approaches that enhance postoperative rehabilitation and pain control—remains a high priority in pain medicine.

Notably, immersive virtual reality (IVR) has emerged as a non-invasive adjunctive therapy with demonstrated potential in alleviating pain and improving neural function across various neuropathic pain conditions, including phantom limb pain, post-stroke neuropathic pain, and neuropathic pain following spinal surgery.15

Given that ZAP shares similar neuropathic mechanisms with these conditions,4,16 we developed an IVR based neurorehabilitation system and integrated it as a complementary strategy to existing clinical management for ZAP. In this study, patients will receive this adjunctive IVR neuromodulation regimen following PRF treatment. We aim to investigate whether this combined approach can further optimize current ZAP management and improve patients’ overall quality of life by alleviating residual pain and enhancing functional rehabilitation.

Materials and Methods Study Design

This is a prospective, parallel-group, single-center randomized controlled trial. The protocol has been developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines,17 and the study results will be reported following the CONSORT Extension for Pragmatic Trials.18 The trial comprises a 1-week treatment phase and a 2-month follow-up phase.

Learning Environment and Recruitment

This trial will be conducted at Pudong Gongli Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China. Participants will be recruited from November 2025 to December 2026 among inpatients and outpatients attending the Department of Pain Management. Eligible participants must meet all of the following inclusion criteria: (1) aged ≥18 years; (2) confirmed diagnosis of Zoster-associated pain; (3) disease duration >2 weeks; (4) scheduled to undergo pulsed radiofrequency therapy; (5) Numerical Rating Scale (NRS) score ≥4 prior to treatment or presence of significant adverse drug reactions to current pharmacotherapy; (6) adequate cognitive function to complete the study questionnaires; and (7) voluntary provision of written informed consent.

Participants will be excluded if they present with any of the following: (1) severe concomitant cardiac, pulmonary, hepatic, or renal insufficiency; (2) coagulation disorders or local infection at the treatment site; (3) cognitive impairment that precludes effective communication; (4) pregnancy or lactation; (5) high myopia exceeding 600 diopters or other ocular diseases that may interfere with VR immersion; or (6) a known predisposition to motion sickness.

Informed Consent and Ethic

The study will be conducted in strict compliance with the ethical principles of the Declaration of Helsinki and has received approval from the Ethics Committee of Pudong Gongli Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China (approval number: GLYY1s2025-092). In accordance with ethical principles, written informed consent will be obtained from all eligible participants prior to enrollment. Before signing, each participant will receive both written information and an oral explanation detailing the study’s objectives, procedures, time commitment, potential risks and benefits, and the right to withdraw at any time without prejudice to their subsequent medical care.

Sample Size Calculation

The sample size was calculated using G*Power 3.1.9.2 software. Based on this primary endpoint, a two-tailed independent-samples t-test was specified with a significance level of α = 0.05, a statistical power (1−β) of 0.90, and an effect size of Cohen’s d = 0.85, informed by Gu et al19 who reported a comparable effect size in patients with ZAP receiving peripheral neuromodulation combined with cognitive therapy. This estimate is also consistent with meta-analytic evidence from Lier et al (2023),20 who reported a pooled SMD of −0.65 (95% CI −0.76 to −0.54) across 122 RCTs, and a larger effect in chronic pain subgroups (SMD = −0.88, 95% CI −1.30 to −0.46), supporting the plausibility of d = 0.85.

The allocation ratio was set at 1:1. A priori power analysis indicated that 31 participants would be required per group, yielding a total sample of 62 participants. Considering a 15% dropout rate, 80 participants (40 per group) were ultimately enrolled. The G*Power output showed that the actual power of the test under this design was 0.909.

We acknowledge that this effect size was extrapolated from a related but not identical intervention paradigm, representing an inherent limitation of the present sample size estimation.

Randomization and Allocation Concealment

Eligible participants will be randomly assigned in a 1:1 ratio to either the control group or the experimental group using simple randomization. The randomization sequence will be generated using the R statistical software (version 4.4.2), with the sample function employed to ensure completely random allocation. A fixed random seed will be set to guarantee the reproducibility of the sequence.

Allocation concealment will be achieved using sequentially numbered, opaque, sealed envelopes. The envelopes will be numbered in accordance with the randomization sequence and will be prepared and maintained by an independent researcher who will not be involved in participant recruitment or outcome assessment. Once a participant meets all eligibility criteria and provides written informed consent, an independent research coordinator—who is not involved in the intervention or outcome evaluation—will open the next envelope in sequence and assign the participant to the corresponding group based on the allocation indicated inside. This process will ensure that the allocation sequence remains concealed from both the recruiting clinicians and the investigators throughout the entire trial.

Blinding Design

To minimize measurement bias, this study employs a strict blinded design. The experimental and control groups will use the same virtual reality device (Pico Ultra 4), and the presentation and operational procedures of the intervention will be highly similar across groups. Although inherent differences in interactivity exist, both groups use the same headset, and treatment allocation is not directly disclosed to patients or outcome assessors. Owing to the nature of the interventions, the treating clinicians cannot be blinded to group assignment; however, they will not be involved in outcome assessments. Statisticians will receive a de identified dataset after the database has been locked and will conduct the analyses while blinded to group allocation until the final unblinding.

In addition, emergency unblinding envelopes have been prepared and will be opened only in accordance with the protocol in the event of life-threatening emergencies; any unblinding events will be documented in detail.

Flowchart

The research flowchart is shown in Figure 1.

Figure 1 Research flowchart.

Abbreviations: NRS, Numerical Rating Scale; HADS, Hospital Anxiety and Depression Scale; SF-12, Short Form-12 Health Survey; PSQI, Pittsburgh Sleep Quality Index; VR, Virtual Reality; PRF, Pulsed Radiofrequency.

Treatment Protocol Basic Treatment

All subjects will receive standardized baseline pharmacological treatment and nerve pulse radiofrequency therapy in accordance with the clinical practice guidelines and nursing protocols for herpes zoster–associated neuropathic pain. The CT guided PRF procedure is performed as follows. The patient is placed in a prone position on the operating table, followed by routine skin disinfection and sterile draping. A positioning grid is placed at the designated puncture site, and CT guidance is used to confirm and precisely target the dorsal root ganglion within the intervertebral foramen. The skin entry point adjacent to the corresponding spinous process is selected, and the puncture needle is advanced along the trajectory marked by the positioning grid. After local infiltration anesthesia, the needle is advanced along the marked line. Under real time CT guidance, the needle tip is gradually directed to the inferolateral margin of the transverse process and subsequently, under CT fluoroscopy, positioned above the intervertebral foramen. The radiofrequency generator is then connected, and the impedance around the needle tip is tested. Electrophysiological localization is performed to confirm the accuracy of the target. Once accuracy is confirmed, pulsed radiofrequency therapy is delivered using the following parameters: 42°C, 2 Hz, for 6 minutes. Throughout the procedure, the patient’s blood pressure, heart rate, and oxygen saturation are dynamically monitored, and subjective symptoms are observed. Postoperatively, pressure is applied to the puncture site for 1–2 minutes, followed by sterile dressing coverage and a 10-minute observation period. If no adverse reactions occur, the patient is returned to the ward. Baseline pharmacotherapy includes pregabalin, gabapentin, and other relevant medications as clinically indicated. All procedures will be performed by the same pain medicine physician and a nurse throughout the trial to ensure consistency.

Therapeutic Environment and Intervention Devices

The intervention will be delivered using the PICO 4 Ultra mixed reality device. The device is equipped with a Qualcomm Snapdragon XR2 Gen 2 processor and features a per eye resolution of 2160 × 2160 pixels with a 90 Hz refresh rate. It supports an interpupillary distance adjustment range of 59 to 72 mm, weighs approximately 580 g, and incorporates a front to back balanced design to ensure wearing comfort during extended use. Additionally, the device enables real time data synchronization and monitoring via Wi Fi and Bluetooth connectivity. Prior to each intervention, device parameters will be adjusted according to the patient’s individual circumstances, and the customized immersive neuromodulation system will be loaded. Patients will wear the device in a comfortable seated position. After each use, the device’s lenses and facial contact components will be thoroughly cleaned and disinfected to ensure both safety and consistency of the intervention across sessions.

Prior to the formal trial, a pilot study was conducted with 10 healthy volunteers to evaluate usability and tolerability. System usability was assessed using the System Usability Scale (SUS),21 and visually induced motion sickness was evaluated using the Simulator Sickness Questionnaire (SSQ).22

Experiment Group

For details on the program content and specific interventions, see Table 1.

Table 1 Program Content

Control Group

Participants in the control group will view pre-recorded relaxation videos featuring scenic landscapes, including dynamic footage of natural scenery, forests, lakes. The audio track will consist of ambient sounds or light music that matched the visual content. Importantly, the videos will not include any therapeutic verbal instructions, guided imagery, or content related to neural repair, ensuring that the control condition serves as a neutral visual auditory stimulus without specific therapeutic intent.

Frequency of Intervention and Treatment Adherence

The intervention will be administered once daily for 7 consecutive days, with each session lasting 10–15 minutes. Researchers will monitor the entire process in real time via tablet devices. Prior to the first intervention, participants will receive standardized training on device operation. Throughout the treatment period, researchers will conduct regular ward visits to address any questions and to monitor device usage, thereby ensuring adherence to the protocol. To further preserve allocation concealment, all participants will be instructed to refrain from discussing the intervention details with each other throughout the study period.

Data Collection and Analysis Baseline Data

Baseline data will be collected at the time of patient enrollment and will include a comprehensive record of the patients’ demographic characteristics and pre-treatment clinical status. Specifically, the following information will be recorded: patient initials, age, sex; disease related baseline data, including pain location, date of onset, treatment date, and type of injury; pre-intervention scores on the Numerical Rating Scale (NRS), Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), and 12 Item Short Form Health Survey (SF 12).

Primary Outcome Measures Numeric Rating Scale

The Numeric Rating Scale (NRS) is an instrument used to assess self-reported pain intensity, which is sensitive to changes in the patient’s pain level. The scale ranges from 0 to 10 points, where 0 represents “no pain” and 10 indicates “the most severe pain imaginable”.23

Secondary Outcome Measures Pittsburgh Sleep Quality Index

The PSQI is a self‑administered questionnaire comprising 19 items that assess seven domains of sleep quality (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medications, and daytime dysfunction). Each domain is scored 0–3, with a global score ranging from 0 to 21; higher scores reflect worse sleep quality (0–7: good; 8–14: moderate; 15–21: poor).24

Hospital Anxiety and Depression Scale

The Hospital Anxiety and Depression Scale (HADS) comprises 14 items divided into two independent subscales: the Anxiety Subscale (HADS-A) and the Depression Subscale (HADS-D), each containing 7 items. The total score for each subscale ranges from 0 to 21, with scores of 0–7 considered within the normal range, 8–10 suggestive of mild anxiety or depression, 11–14 indicating moderate levels, and 15–21 indicating severe anxiety or depression, respectively.25

12-Item Short Form Health Survey

The 12-Item Short Form Health Survey (SF-12) is a self‑administered questionnaire comprising 12 items that evaluate eight health domains: general health, physical functioning, role limitations due to physical health problems, bodily pain, vitality, social functioning, role limitations due to emotional problems, and mental health. The assessment yields two summary component scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Higher scores indicate better health status, with scores normalized to a general population mean of 50 and a standard deviation of 10.26

Security Assessment

Throughout the trial, all adverse events will be prospectively documented by physicians and outcome assessors using a standardized case report form. Expected adverse events may include infection, eye strain, dizziness, nausea, vomiting, and worsening of pain and related discomfort. For safety reasons, medical staff will closely monitor the entire treatment process and provide prompt assistance as needed.

Measurement Time Point

Outcome measures will be collected at multiple time points, as summarized in Table 2. The primary outcome—pain intensity assessed by the Numerical Rating Scale (NRS)—will be measured at all five scheduled time points. The secondary outcomes, including sleep quality (PSQI), emotional status (HADS), and health‑related quality of life (SF‑12), will be assessed at enrollment, immediately after radiofrequency treatment, at discharge, and at 1 and 2 months post‑discharge.

Table 2 Evaluation Time Point

Confidentiality

To ensure participant confidentiality, all data will be processed in accordance with strict de-identification protocols. Each participant will be assigned a unique study code to replace any personally identifiable information in the study records. Informed consent forms containing identifying information will be stored securely and separately, apart from all study data (including case report forms). Consequently, all datasets used for statistical analysis and reporting will be fully de identified.

Statistical Analysis

All data analyses will be performed using SPSS version 26.0, with a significance level set at a two-sided P < 0.05. Descriptive statistical analyses will be calculated for baseline characteristics of all participants. Continuous variables will be tested for normality using the Shapiro–Wilk test; normally distributed will be expressed as mean ± SD, whereas non-normally data will be presented as median (percentile). Categorical variables will be summarized as frequencies and percentages. Intergroup comparisons of baseline characteristics will be conducted using independent samples t test, Mann–Whitney U-test, χ2-test, or Fisher’s exact test, as appropriate. Both the primary outcome (NRS) and secondary outcomes (HADS, PSQI, SF-12) will be analyzed using generalized estimating equations (GEE). The model assumes that the dependent variable follows a normal distribution.

Fixed effects include group, time (T0–T4), and the group × time interaction term, and the optimal working matrix is selected based on the QIC criterion. All analyses will be conducted according to the intention to treat (ITT) principle. GEE provides valid estimates under the assumption that missing data are missing completely at random (MCAR), and as such, no additional imputation will be performed for missing outcome data. If the group × time interaction term is statistically significant, simple effects analyses will be performed to compare between group differences at each time point, and P values will be adjusted using the Bonferroni correction to control for Type I error.

Discussion

ZAP is a common form of neuropathic pain with complex clinical manifestations. Its pathogenesis involves multi-level peripheral nerve inflammation and abnormal remodeling of central pain processing pathways.4,5 Current clinical management strategies encompass a variety of treatment approaches, including pharmacotherapy, minimally invasive interventional therapies, traditional Chinese medicine, and physical therapy.4,27 However, clinical experience suggests that a substantial proportion of patients with severe lesions continue to experience residual symptoms—such as persistent localized dull pain and tingling—even after receiving comprehensive treatment that achieves significant reductions in overall pain intensity.

This persistent residual pain is highly prone to progressing into postherpetic neuralgia (PHN), which further complicates clinical management and profoundly impairs patients’ physical and psychological well-being. Accordingly, addressing this residual pain has become both a key priority and a major challenge in the contemporary clinical management of ZAP.

PRF is a well-established neuromodulation technique and a key strategy for treating ZAP.28 Its clinical mechanism of action has been extensively characterized: PRF exerts analgesic effects by inhibiting aberrant peripheral nerve discharges, reducing neuronal inflammatory responses, and promoting neural adaptation.29,30 However, current understanding of the extent to which PRF influences the progression of postherpetic neuralgia remains limited.

In recent years, virtual reality (VR) technology has been increasingly applied in the clinical management of chronic neuropathic pain.31 Accumulating evidence suggests that VR based interventions not only provide analgesic effects but may also induce adaptive neuroplasticity,32,33 offering a novel approach to optimizing ZAP treatment and potentially mitigating disease chronification. Based on these considerations, we developed an immersive virtual reality neurorehabilitation system and designed an innovative combined treatment modality—CT-guided PRF followed by an IVR based neurorehabilitation program—aimed at optimizing pain management in ZAP. Through a rigorous randomized controlled trial design, the present study will investigate the efficacy of this integrated system and validate its clinical value in patients with postherpetic neuralgia. The immersive virtual reality neurorehabilitation system developed for this study comprises three core functional modules.

First, the system delivers comprehensive patient education regarding the pathogenesis of ZAP, the entire treatment process, and the post treatment home rehabilitation plan. Second, the system incorporates a standardized three-dimensional (3D) model of the human nervous system. Through interactive visualization, patients can accurately identify the distribution and extent of their nerve damage, thereby deepening their understanding of their own neuroanatomical status and establishing a foundation for personalized rehabilitation interventions. Third, the system provides personalized neural stimulation protocols that, when combined with the patient’s actual treatment experience, reawaken somatosensory memory and guide patients through targeted neural repair imagery training. This module continuously presents visual cues of neural repair and injury resolution, reinforcing the internal sensory experience of “ongoing nerve recovery”.

The analgesic mechanisms underlying the IVR‑based neurorehabilitation system are multifaceted and can be understood through several complementary theoretical frameworks.

McConnell et al (2024) demonstrated that immersive VR mediated pain neuroscience education (PNE) can render abstract neural mechanisms tangible,34 deepen patients’ understanding of their pathology, reduce pain catastrophizing and fear avoidance behaviors, promote cognitive reappraisal, and foster adaptive pain beliefs.35 These findings provide both theoretical and clinical feasibility support for the design of the first two modules of our system—specifically, patient education and the visualization of neuroanatomical structures. Complementary to the cognitive frameworks discussed above, the embodied cognition framework posits that pain is not merely a signal of tissue damage, but rather a deeply embodied experience shaped by bodily representations and the sense of body ownership.36 IVR, through the use of immersive virtual avatars, can induce a sense of embodiment that effectively diverts cognitive attention away from nociceptive processing, thereby producing immediate analgesic effects (Hoffman et al, 2020).37,38 This body centered mechanism operates in parallel with the cognitive educational pathways described earlier, jointly contributing to the analgesic effects of the IVR intervention. Second, the predictive coding model of pain posits that in chronic pain states, persistent and uncorrected prediction errors lead to a maladaptive overestimation of pain intensity.39 The virtual reality experimental platform developed by Palmisani et al (2025) demonstrated that by manipulating pain expectations through VR to artificially generate controllable prediction errors, it is possible to recalibrate the predictive coding of pain, thereby providing a reliable paradigm for interventions targeting neuropathic pain associated with central sensitization.40 This framework is particularly relevant to our third module—personalized neural stimulation—as it suggests that IVR can be harnessed not merely as a passive distraction tool, but as an active agent for recalibrating maladaptive pain predictions at the cognitive level.15,37,38 Emerging evidence suggests that immersive virtual reality can promote neuroplastic changes in pain-related neural circuits, including the modulation of insulo-thalamic connectivity and the engagement of top-down endogenous analgesic systems.32,33,41 These mechanisms—operating at cognitive, bodily, epistemic, and neural levels—are likely to act synergistically and may have contributed to the analgesic and rehabilitative effects observed following the combined PRF+IVR intervention.

By integrating these complementary pathways, the present study offers a comprehensive mechanistic framework for understanding how IVR may serve as an effective adjunct to PRF in the management of ZAP.

Several limitations of this study should be acknowledged. First, the reliance on subjective self-report scales, without the inclusion of objective neurobiological biomarkers (eg, functional magnetic resonance imaging or inflammatory markers), limits the ability to quantify changes at the neural level. Second, the single center design and relatively small sample size may limit the generalizability of the findings, underscoring the need for larger multicenter trials. Third, the absence of a PRF only control group restricts the ability to isolate the specific additive efficacy of IVR, while the 2 month follow up period precludes assessment of long-term treatment durability and its potential role in preventing progression to PHN. Despite these limitations, the present study is expected to provide valuable preliminary evidence supporting the integration of IVR into standard PRF based management for ZAP. Future studies with extended follow up and biomarker-based assessments are warranted to further validate the long-term benefits of this combined approach.

Study Registration

Chinese Clinical Trial Registry (ChiCTR2100054592).

Acknowledgments

We sincerely thank all the participants who made this study possible.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by the Pudong Gongli Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China (Award Number: 2025-GLSHLH-03). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure

The author(s) declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

1. Bricout H, Haugh M, Olatunde O, Gil Prieto R. Herpes zoster-associated mortality in Europe: a systematic review. BMC Public Health. 2015;15:466. doi:10.1186/s12889-015-1753-y

2. Johnson RW. Zoster-associated pain: what is known, who is at risk and how can it be managed? Herpes. 2007;14(suppl 2):30–11.

3. Johnson RW, Alvarez-Pasquin M-J, Bijl M, et al. Herpes zoster epidemiology, management, and disease and economic burden in Europe: a multidisciplinary perspective. Ther Adv Vaccines Immunother. 2015;3(4):109–120. doi:10.1177/2051013615599151

4. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9(8):807–819. doi:10.1016/S1474-4422(10)70143-5

5. Ma YC, Kang ZB, Shi YQ, Ji WY, Zhou WM, Nan W. The complexity of neuropathic pain and central sensitization: exploring mechanisms and therapeutic prospects. J Integr Neurosci. 2024;23(5):89. doi:10.31083/j.jin2305089

6. Ünal HA, Ögüt ND, Güler E, Alptekin A. Pain type and neuropathic pain components in acute herpes zoster. Agri. 2024;36(2):100–105. doi:10.14744/agri.2023.03743

7. Patil A, Goldust M, Wollina U. Herpes zoster: a review of clinical manifestations and management. Viruses. 2022;14(2):192. doi:10.3390/v14020192

8. Koshy E, Lu MT, Kumar H, Wu JB. Epidemiology, treatment and prevention of herpes zoster: a comprehensive review. Indian J Dermatol Venereol Leprol. 2018;84(3):251–262. doi:10.4103/ijdvl.IJDVL_1021_16

9. Yu SY, Fan BF, Yang F, et al. Patient and economic burdens of postherpetic neuralgia in China. Clinicoecon Outcomes Res. 2019;11:539–550. doi:10.2147/CEOR.S203920

10. Johnson RW, Bouhassira D, Kassianos G, Leplège A, Schmader KE, Weinke T. The impact of herpes zoster and post-herpetic neuralgia on quality-of-life. BMC Med. 2010;8:37. doi:10.1186/1741-7015-8-37

11. Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open. 2014;4(6):e004833. doi:10.1136/bmjopen-2014-004833

12. Rui M, Han ZX, Xu LS, Yao M. Effect of CT-guided repeated pulsed radiofrequency on controlling acute/subacute zoster-associated pain: a retrospective cohort study. Pain Ther. 2024;13(1):99–112. doi:10.1007/s40122-023-00567-1

13. Ding Y, Li H, Hong T, Zhao R, Yao P, Zhao G. Efficacy and safety of computed tomography-guided pulsed radiofrequency modulation of thoracic dorsal root ganglion on herpes zoster neuralgia. Neuromodulation. 2019;22(1):108–114. doi:10.1111/ner.12858

14. Chen L, Li J, Liu H, Yang P, Zuo Y, Ye L. Interventions for zoster-associated pain: a retrospective study based on the clinical database. Front Neurol. 2022;13:1056171. doi:10.3389/fneur.2022.1056171

15. Maggio MG, Bonanno M, Calderone A, et al. Remapping body representation using virtual reality in chronic neuropathic pain: systematic review. J Med Internet Res. 2025;27:e71074. doi:10.2196/71074

16. Finnerup NB, Kuner R, Jensen TS. Neuropathic pain: from mechanisms to treatment. Physiol Rev. 2021;101(1):259–301. doi:10.1152/physrev.00045.2019

17. Chan AW, Boutron I, Hopewell S, et al. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. Nat Med. 2025;31(6):1784–1792. doi:10.1038/s41591-025-03668-w

18. Hopewell S, Chan AW, Collins GS, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123. doi:10.1136/bmj-2024-081123

19. Gu GL, Sun LH, Hu LH, et al. Effect of cognitive therapy on patients with herpes zoster neuralgia after short-term spinal cord stimulation. Guizhou Med Univ. 2022;47(8):916–920. doi:10.19367/j.cnki.2096-8388.2022.08.008

20. Lier EJ, Steggink EM, ten Broek RPG, van Goor H, de Vries M. Effect modifiers of virtual reality in pain management: a systematic review and meta-regression analysis. Pain. 2023;164(8):1658–1665. doi:10.1097/j.pain.0000000000002883

21. Lewis JR. The system usability scale: past, present, and future. Int J Hum. 2018;34(7):577–590. doi:10.1080/10447318.2018.1455307

22. Bimberg P, Weissker T, Kulik A. On the usage of the simulator sickness questionnaire for virtual reality research. In: 27th IEEE Conference on Virtual Reality and 3D User Interfaces (IEEE VR); Atlanta, GA: IEEE; 2020. doi:10.1109/VRW50115.2020.000178.

23. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain visual analog scale for pain (VAS pain), numeric rating scale for pain (NRS pain), McGill pain questionnaire (MPQ), short-form McGill pain questionnaire (SF-MPQ), chronic pain grade scale (CPGS), short form-36 bodily pain scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res. 2011;63(suppl 11):S240–S252. doi:10.1002/acr.20543

24. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213. doi:10.1016/0165-1781(89)90047-4

25. Fomenko A, Dümmler D, Aktürk Z, et al. Hospital Anxiety and depression scale anxiety subscale (Hads-A) for detecting anxiety disorders in adults. Cochrane Database Syst Rev. 2025;7(7):CD015456. doi:10.1002/14651858.CD015456

26. Jenkinson C, Layte R, Jenkinson D, et al. A shorter form health survey: can the SF-12 replicate results from the SF-36 in longitudinal studies? J Public Health Med. 1997;19(2):179–186. doi:10.1093/oxfordjournals.pubmed.a024606

27. Aggarwal A, Suresh V, Gupta B, Sonthalia S. Post-herpetic neuralgia: a systematic review of current interventional pain management strategies. J Cutan Aesthet Surg. 2020;13(4):265–274. doi:10.4103/JCAS.JCAS_45_20

28. Abejón D, Reig E. Is pulsed radiofrequency a neuromodulation technique? Neuromodulation. 2003;6(1):1–3. doi:10.1046/j.1525-1403.2003.03009.x

29. Kessels AGH, van Kleef M, Van Zundert J, et al. Pulsed and continuous radiofrequency current adjacent to the cervical dorsal root ganglion of the rat induces late cellular activity in the dorsal horn. Anesthesiology. 2005;102(1):125–131. doi:10.1097/00000542-200501000-00021

30. Vallejo R, Tilley DM, Williams J, Labak S, Aliaga L, Benyamin RM. Pulsed radiofrequency modulates pain regulatory gene expression along the nociceptive pathway. Pain Physician. 2013;16(5):E601–E613. doi:10.36076/ppj.2013/16/E601

31. Selvaraj JS, Prakash H, Augustine TA, Kumar SSK, Velkumar S, Amalraj JA. Immersive virtual reality for neuropathic pain management in spinal cord injury: a randomized controlled trial. J Spinal Cord Med. 2026;49(3):543–555. doi:10.1080/10790268.2025.2514321

32. Corbetta D, Imeri F, Gatti R. Rehabilitation that incorporates virtual reality is more effective than standard rehabilitation for improving walking speed, balance and mobility after stroke: a systematic review. J Physiother. 2015;61(3):117–124. doi:10.1016/j.jphys.2015.05.017

33. Wankhede NL, Koppula S, Ballal S, et al. Virtual reality modulating dynamics of neuroplasticity: innovations in neuro-motor rehabilitation. Neuroscience. 2025;566:97–111. doi:10.1016/j.neuroscience.2024.12.040

34. McConnell R, Lane E, Webb G, LaPeze D, Grillo H, Fritz J. A multicenter feasibility randomized controlled trial using a virtual reality application of pain neuroscience education for adults with chronic low back pain. Ann Med. 2024;56(1):2311846. doi:10.1080/07853890.2024.2311846

35. Sánchez-Robalino A, Sinchi-Sinchi H, Ramírez A. Effectiveness of pain neuroscience education in physical therapy: a systematic review and meta-analysis. Brain Sci. 2025;15(6):658. doi:10.3390/brainsci15060658

36. Kiverstein J, Kirchhoff MD, Thacker M. An embodied predictive processing theory of pain experience. Rev Philos Psychol. 2022;13(4):973–998. doi:10.1007/s13164-022-00616-2

37. Matamala-Gomez M, Donegan T, Bottiroli S, Sandrini G, Sanchez-Vives MV, Tassorelli C. Immersive virtual reality and virtual embodiment for pain relief. Front Hum Neurosci. 2019;13:279. doi:10.3389/fnhum.2019.00279

38. Hoffman HG. Interacting with virtual objects via embodied avatar hands reduces pain intensity and diverts attention. Sci Rep. 2021;11(1):10672. doi:10.1038/s41598-021-89526-4

39. Chen ZS. Hierarchical predictive coding in distributed pain circuits. Front Neural Circuits. 2023;17:1073537. doi:10.3389/fncir.2023.1073537

40. Palmisani F, Thiyagarajan JSP, Horsey J, Hughes SW, Medina S. Investigating the influence of experimentally induced secondary hyperalgesia on pain prediction error encoding in healthy individuals: a novel virtual reality protocol. Eur J Pain. 2025;29(9):e70113. doi:10.1002/ejp.70113

41. Shi Y, Wu W. Multimodal non-invasive non-pharmacological therapies for chronic pain: mechanisms and progress. BMC Med. 2023;21(1):372. doi:10.1186/s12916-023-03076-2