Functional brain connectivity correlates of pain relief during virtual reality exposure in cancer patients.

Introduction

Cancer-related pain is prevalent and debilitating, greatly reducing quality of life ( 1 , 2 ). Virtual reality (VR) is emerging as a non-pharmacologic pain relief approach through attention redirection and immersive distraction ( 3 – 5 ). VR may relieve pain by creating an immersive environment that redirects attention away from nociceptive input and pain perception, while promoting relaxation and emotional engagement. In oncology populations, VR has also been explored as a supportive intervention for cancer-related symptom management, including in advanced cancer patients receiving home-based care ( 6 ). Although VR's analgesic effects are behaviorally documented, the underlying brain mechanisms, especially in cancer patients, remain less understood ( 4 ). Functional near-infrared spectroscopy (fNIRS) provides a non-invasive means to assess brain activation and functional connectivity during pain modulation, offering mechanistic insights to personalize VR therapies ( 4 ).

Pain perception involves distributed brain regions that process sensory, cognitive, and emotional components of pain ( 7 , 8 ). Somatosensory and parietal regions contribute to sensory localization and intensity processing, while the prefrontal cortex and superior frontal regions are involved in attention, cognitive control, and top-down modulation of pain ( 7 , 9 ). Deeper regions such as the anterior cingulate cortex and insula are also important components of salience and affective pain-processing networks, although they are not directly accessible with fNIRS ( 10 , 11 ). By redirecting attention and promoting immersion, VR may alter activity and connectivity within these cortical pain-modulatory networks ( 12 , 13 ).

fNIRS is a non-invasive neuroimaging technique that monitors cortical hemodynamics during real-world tasks. By measuring oxygenated hemoglobin (HbO) changes, it reveals how specific brain regions are activated and interact during pain perception and modulation.

Coherence analysis measures frequency-specific coupling of fNIRS signals (e.g., HbO) between brain regions, providing an estimate of functional connectivity, or coordinated activity among regions within a brain network ( 14 , 15 ).

In pain, altered functional connectivity may indicate disrupted or compensatory brain responses, whereas a shift toward pain-free patterns may signal effective relief ( 8 , 16 , 17 ). Recognizing these patterns helps identify neurophysiological biomarkers of treatment response and informs the development of personalized, brain-based pain management strategies, especially for chronic or treatment-resistant cases.

Altered functional connectivity is common in chronic pain, reflecting disrupted interactions between pain-processing and modulatory brain regions ( 8 , 18 , 19 ). In cancer care, multimodal pharmacologic pain management is often limited by side effects, tolerance, incomplete response, or patient preference, highlighting the need for effective non-invasive complementary approaches ( 20 ).

Understanding the neural correlates associated with pain changes during immersive VR exposure may help clarify how VR-based interventions influence pain-related brain networks and may inform future development of personalized digital symptom-management strategies.

Therefore, this exploratory single-arm study examined whether short-term pain reduction during a single VR-based relaxation/distraction session is associated with fNIRS-derived cortical activation and functional connectivity changes in cancer patients with chronic pain. We focused on oxygenated hemoglobin activity and coherence-based functional connectivity across cortical regions involved in pain perception, attention, and cognitive modulation.

Methods

Forty-one adult cancer patients (33 males, 8 females; mean age = 62 ± 11.3 years; BMI = 29 ± 8.2) with chronic cancer-related pain were recruited from the outpatient clinic of the Division of Pain Medicine at Roswell Park Comprehensive Cancer Center. All patients were receiving multimodal pharmacological therapy but reported inadequate pain relief. Cancer type was defined based on the combination of primary disease site and histologic diagnosis and is summarized in Table 1 . Participants experienced chronic cancer-related pain lasting longer than 9 months at the time of enrollment, with neuropathic and/or somatic components, consistent with mixed-mechanism cancer pain commonly observed in oncology populations. Although these pain states originate from peripheral mechanisms, chronic neuropathic and somatic pain are increasingly recognized to involve altered large-scale brain network dynamics, often referred to as brain network pain .

Participants had no neurological/psychiatric disorders, brain metastases, head implants, or pregnancy, and removed items obstructing fNIRS contact. Those with hypersensitivity to flashing lights/motion, impaired stereoscopic vision, severe hearing loss, or nausea/dizziness risk were excluded.

Participants completed a 9-minute immersive VR session [Oceania program, Meta Store ( 21 )] while fNIRS data were recorded using the Dual Brite system with Oxysoft 3.3 software (Artinis Medical Systems®, Netherlands). The VR intervention consisted of a single, immersive relaxation/distraction session delivered through the Oceania application using a Meta Quest® headset. The program presented a calming ocean-based virtual environment designed to promote relaxation and attentional engagement away from pain. Participants wore the VR headset while seated and were instructed to view and engage with the virtual environment for the full 9-minute session. No sham VR or non-VR control condition was used in this exploratory single-arm study; therefore, the analysis focused on within-subject changes in pain ratings and fNIRS-derived brain activation/connectivity during VR exposure relative to the pre-VR resting baseline.

The 44-channel setup covered multiple cortical regions ( Figure 1 ). The parietal lobe includes superficial primary somatosensory cortex (S1) areas accessible to fNIRS, which detects hemodynamic changes up to ∼2 cm beneath the scalp, enabling monitoring of surface-level activity in pain-related regions such as S1.

Channels 1–24 were assigned to the PFC, 25–29 to the right parietal cortex (RPC), 30–39 to the SFG, and 40–44 to the left parietal cortex (LPC) ( 4 ). A 10-minute resting-state fNIRS recording was obtained prior to the VR intervention to establish baseline cortical activity.

fNIRS signal processing

Signals were motion-corrected, bandpass-filtered (0.01–0.2 Hz), converted to HbO via the modified Beer–Lambert law ( 22 ), normalized, and baseline-corrected relative to the pre-VR resting state to isolate changes observed during VR exposure. MATLAB R2022a and the NIRS Toolbox pipeline were used for signal processing. For each subject, the pre-VR baseline mean was subtracted from VR data to quantify relative HbO changes from the intervention.

fNIRS-based features

Average HbO amplitudes served as the activation metric, and preprocessed HbO signals were used to compute functional connectivity via coherence analysis. Magnitude-squared coherence (MSC) was computed pairwise between fNIRS channels for the HbO signals to assess functional connectivity changes during VR.

Correlation analysis

Pain severity ratings were collected before and after VR using the FACES Pain Scale-Revised (FPS-R) tool ( 23 ), and percent reduction was calculated as [ p a i n p r e − V R − p a i n p o s t − V R p a i n p r e − V R ] × 100 .

Pearson correlations were calculated between extracted metrics (mean activation and functional connectivity) and percent pain reduction, with false discovery rate (FDR) correction for multiple comparisons. Statistical significance was set at p < 0.05.

All channel-level and channel-pair analyses were performed across the full set of recorded fNIRS channels in an unbiased manner, and only results surviving FDR correction were reported.

Behavioral statistical analysis

Because pain scores were not normally distributed (Shapiro–Wilk test), changes in perceived pain severity before and after the VR intervention were assessed using the Wilcoxon signed-rank test. Statistical significance was set at p < 0.05.

This study was designed as an exploratory investigation to examine associations between short-term pain reduction during VR exposure and fNIRS-derived cortical activation and functional connectivity in a cancer population. As such, a formal a priori sample size calculation was not performed. The sample size was determined pragmatically and aligns with prior fNIRS studies of pain and analgesia, which typically use moderate cohorts to explore neural mechanisms rather than confirm definitive effects.

For example, prior fNIRS studies examining pain and cortical activity during VR exposure have typically included sample sizes ranging from approximately 15 to 60 participants ( 24 – 26 ). Accordingly, the present findings are intended to be exploratory and hypothesis-generating, rather than confirmatory.

Results

Average pain scores for 41 cancer patients with chronic pain were 4 ± 2.01 before VR and 2 ± 1.59 after VR. Perceived pain severity significantly decreased following the VR intervention (Wilcoxon signed-rank test, p < 0.001). More than 75% of participants experienced pain relief exceeding 30%, a threshold commonly considered clinically meaningful ( 27 ).

Significant negative correlations were observed between functional connectivity metrics, derived from HbO signals during VR engagement, and pain relief ( Table 2 ), suggesting that lower functional connectivity, that is, reduced synchronization across cortical regions, is associated with greater analgesia.

Significant associations were observed between average HbO activation and pain reduction at two individual channels. Specifically, higher pain relief was significantly correlated with lower average HbO activation levels at channel 11 (PFC; r = –0.316, p = 0.044) and channel 17 (PFC; r = –0.354, p = 0.023). These channels were reported because they showed statistically significant correlations after FDR correction in an unbiased analysis across all recorded channels; no channels were selected a priori , supporting the robustness of the observed associations.

The observed correlations were of moderate magnitude (|r| ≈ 0.3–0.4), suggesting meaningful associations despite the exploratory nature of the study.

Discussion

The primary contribution of this study is methodological, demonstrating the feasibility of integrating immersive VR with fNIRS-based functional connectivity analysis in a cancer population, rather than establishing VR-specific analgesic mechanisms. This study observed that short-term pain reduction during VR exposure in cancer patients was associated with decreased functional connectivity between the prefrontal cortex, superior frontal gyrus, and parietal lobes, as well as reduced prefrontal cortical activation. These findings suggest that immersive VR may be accompanied by changes in attentional and cortical network dynamics related to pain perception and cognitive control, although causal mechanisms cannot be inferred.

The cancer pain experienced by participants in this study comprised neuropathic and/or somatic components, reflecting mixed-mechanism chronic pain ( 28 , 29 ). While these pain types originate from peripheral tissue or nerve pathology, chronic pain states are known to involve maladaptive reorganization of large-scale brain networks, including the salience network and default mode network ( 8 , 16 , 18 , 30 , 31 ). Excessive salience attribution to nociceptive input and persistent engagement of self-referential processing have been implicated in the maintenance of chronic pain, even when peripheral drivers remain stable ( 8 , 16 , 32 ). The reduced functional connectivity and prefrontal activation observed during VR engagement in this study are consistent with a transient suppression of these centrally mediated network processes ( 7 , 13 , 32 ).

The findings suggest that short-term pain reduction observed during VR exposure was associated with reduced cortical synchrony in specific brain regions. These neural observations occurred alongside a statistically significant decrease in self-reported pain severity following VR, indicating that the functional connectivity changes were observed in the context of concurrent behavioral pain changes. Accordingly, these findings should be interpreted as correlational rather than VR-specific causal effects, as the single-arm design does not allow exclusion of nonspecific factors such as expectancy, time effects, or spontaneous pain fluctuations. Chronic pain often involves increased or less flexible connectivity among pain-processing and modulatory regions ( 8 , 32 ), and VR distraction may disrupt these patterns, fostering a more flexible brain network state. Reduced connectivity, particularly between prefrontal, parietal, and superior frontal regions, likely reflects a cognitive shift from internally focused pain monitoring to externally focused engagement. This aligns with evidence that decreased coupling in these networks is associated with reduced pain awareness and better analgesia ( 7 , 9 , 33 ). In this context, decreased synchrony may indicate effective disengagement of the pain network, consistent with reduced pain ratings. The strongest effects were seen in channels spanning the prefrontal cortex and superior frontal gyrus, with additional significant associations involving parietal regions, supporting the involvement of cortical networks related to attention, cognitive control, and pain modulation ( 33 , 34 ).

Beyond changes in individual brain regions, the observed pattern of connectivity alterations aligns with known large-scale brain networks involved in chronic pain ( 8 , 18 , 35 ).

Although fNIRS does not directly capture activity in deep cortical structures such as the anterior cingulate cortex or anterior insula, key nodes of the salience network, prefrontal and superior frontal regions measured here are strongly functionally connected to these structures and play a central role in cognitive control, attention, and pain modulation ( 7 , 10 , 11 , 33 ).

Significant negative correlations between pain reduction and HbO levels in two prefrontal cortex channels indicated that greater analgesia was linked to lower PFC activation, possibly reflecting reduced cognitive and emotional burden during VR. The PFC is central to pain processing, emotion regulation, and attention ( 7 , 36 ), and in chronic pain, increased activity is often tied to heightened pain awareness, persistent negative thinking, and distress ( 8 , 32 ). Thus, decreased PFC activation during VR may signal reduced cognitive-emotional engagement with pain, enabling deeper immersion in distraction and greater pain relief.

Prior neuroimaging studies demonstrate that VR-based analgesia is associated with reduced salience network activation and altered coupling between the default mode network and medial frontal cortex, supporting a network-level mechanism of pain relief ( 8 , 12 , 13 , 37 – 40 ). This interpretation is consistent with prior neuroimaging studies using other techniques, including fMRI studies of VR analgesia showing reduced pain-related brain activity, and studies of interventional analgesia in cancer pain showing decreased salience-network connectivity after pain relief ( 13 , 41 ).

Decreased inter-channel functional connectivity, particularly between the PFC and SFG, was significantly correlated with greater pain relief (e.g., channels 15–38: r = –0.429, p = 0.005). These regions are involved in cognitive control, attention regulation, and top-down pain modulation. Reduced connectivity may indicate temporary disengagement of control networks, enabling greater immersion in VR and less cognitive focus on pain. This shift away from self-monitoring and pain-related processing may facilitate analgesia through attentional redirection and emotional detachment.

Combined reductions in PFC activation and its connectivity with other regions indicate diminished top-down modulation during effective VR distraction. These findings support that VR influences both activation and connectivity in pain-modulatory regions, particularly the PFC ( 12 , 42 ).

Reduced functional connectivity may indicate neural decoupling that enables attentional disengagement from pain, consistent with theories that diminished connectivity within cognitive and salience networks facilitate relief by limiting integration of nociceptive inputs. VR shows promise as an immersive, non-pharmacologic analgesic in cancer care, and fNIRS-derived connectivity metrics could help identify likely responders and serve as biomarkers of treatment responsiveness.

Prior research supports this interpretation, showing that reduced functional connectivity within key networks (e.g., frontoparietal cognitive and attention networks) can limit nociceptive signal integration and alleviate pain. In essence, when regions that evaluate and propagate pain become less synchronized, perceived pain intensity or unpleasantness can decrease ( 41 ). Jalon et al. ( 41 ) examined cancer patients undergoing neurosurgical procedures for intractable pain and found that both spinal cordotomy (disrupting sensory nociceptive pathways) and cingulotomy (lesioning the anterior cingulate cortex to target affective pain) produced immediate relief and reduced functional connectivity within the salience network ( 41 ), supporting the role of salience-network connectivity changes in pain relief. Similarly, VR-based analgesia studies show that patients immersed in VR during painful procedures report large pain reductions and display significantly decreased pain-related brain activity on fMRI ( 13 ). These results suggest that VR distraction lessens pain perception by downregulating the connectivity and activity of networks that integrate nociceptive information.

fNIRS-derived biomarkers could identify VR-responsive patients, guide personalized care, reduce pharmacologic burden, and offer a pathway to precise, adaptive, and low-burden pain relief, positioning VR as a safe, scalable, and cost-effective tool in oncology pain management.

Limitations

This pilot study has some limitations. The single-arm design, without a control or sham VR condition, limits our ability to draw causal conclusions about the specific effects of VR. Although baseline-corrected fNIRS measures were used to reference neural changes to each participant's pre-VR resting state and reduce inter-individual variability, this within-subject approach does not replace the need for a parallel control condition.

The relatively small sample size and the use of a single, short VR session restrict generalizability and do not allow evaluation of long-term analgesic effects. Also, pain intensity was assessed only before and immediately after the VR session, which limits the ability to examine temporal dynamics of pain and brain connectivity changes during the intervention. In addition, although fNIRS enables brain activity to be measured during real-world tasks, it is limited to surface cortical regions and cannot directly measure deeper brain structures such as the anterior cingulate cortex or insula, which play important roles in pain-related networks. Finally, correlation-based analyses identify relationships between variables rather than causal effects, and future studies with larger samples and controlled designs are needed.

Code availability statement

No custom code or mathematical algorithm was developed for this study.

Acknowledgments

The authors thank all patients who participated in this study.

Funding Statement

The author(s) declare that financial support was received for this work and/or its publication. This research was supported by Health Research Inc. (HRI) through its in-house Research and Development Program at the Center for Surgical Innovation and by the Roswell Park Alliance Foundation. No award number was provided. The funders had no role in the study design; data collection, analysis, or interpretation; the decision to publish; or the preparation of the manuscript.

Footnotes

Edited by: Tony L. Yaksh , University of California, San Diego, United States

Reviewed by: Yang Wang , University of Maryland, United States

Silvia Varani , Fondazione ANT Italia ONLUS, Italy

Data availability statement

The data that support the findings of this study are available from the corresponding author [SBS] upon reasonable request.

Ethics statement

The studies involving humans were approved by Roswell Park Comprehensive Cancer Center (I-1720121). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

Author contributions

SOS: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Validation, Visualization, Writing – original draft. SaS: Conceptualization, Formal analysis, Methodology, Writing – review & editing. OD-C: Methodology, Validation, Writing – review & editing.

Conflict of interest

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

Generative AI statement

The author(s) declared that generative AI was used in the creation of this manuscript. Element ( A ) of Figure 1 was generated using the ChatGPT 4o AI, which assisted in the creation of visual elements.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

1. Joshy G, Khalatbari-Soltani S, Soga K, Butow P, Laidsaar-Powell R, Koczwara B, et al. Pain and its interference with daily living in relation to cancer: a comparative population-based study of 16,053 cancer survivors and 106,345 people without cancer. BMC Cancer. (2023) 23:774. 10.1186/s12885-023-11214-5

2. Mestdagh F, Steyaert A, Lavand’homme P. Cancer pain management: a narrative review of current concepts, strategies, and techniques. Current Oncology. (2023) 30:6838–58. 10.3390/curroncol30070500

3. Hoffman HG, Chambers GT, Meyer WJ, Arceneaux LL, Russell WJ, Seibel EJ, et al. Virtual reality as an adjunctive non-pharmacologic analgesic for acute burn pain during medical procedures. Ann Behav Med. (2011) 41:183–91. 10.1007/s12160-010-9248-7

4. Shafiei SB, Shadpour S, Pangburn B, Bentley-McLachlan M, de Leon-Casasola O. Pain classification using functional near infrared spectroscopy and assessment of virtual reality effects in cancer pain management. Sci Rep. (2025) 15:8954. 10.1038/s41598-025-93678-y

5. Teh JJ, Pascoe DJ, Hafeji S, Parchure R, Koczoski A, Rimmer MP, et al. Efficacy of virtual reality for pain relief in medical procedures: a systematic review and meta-analysis. BMC Med. (2024) 22:64. 10.1186/s12916-024-03266-6

6. Giannelli A, Moscato S, Ostan R, Pannuti R, Chiari L, Biasco G, et al. Virtual reality for advanced cancer patients assisted at home: a randomized controlled interventional study. Psychooncology. (2024) 33:e6368. 10.1002/pon.6368

7. Bushnell MC, Čeko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. (2013) 14:502–11. 10.1038/nrn3516

8. Kucyi A, Davis KD. The dynamic pain connectome. Trends Neurosci. (2015) 38:86–95. 10.1016/j.tins.2014.11.006

9. Torta DM, Legrain V, Mouraux A, Valentini E. Attention to pain! A neurocognitive perspective on attentional modulation of pain in neuroimaging studies. Cortex. (2017) 89:120–34. 10.1016/j.cortex.2017.01.010

10. Menon V, Uddin LQ. Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct. (2010) 214:655–67. 10.1007/s00429-010-0262-0

11. Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. (2007) 27:2349–56. 10.1523/JNEUROSCI.5587-06.2007

12. Hoffman HG, Richards TL, Coda B, Bills AR, Blough D, Richards AL, et al. Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI. Neuroreport. (2004) 15:1245–8. 10.1097/01.wnr.0000127826.73576.91

13. Hoffman HG, Richards TL, Bills AR, Van Oostrom T, Magula J, Seibel EJ, et al. Using FMRI to study the neural correlates of virtual reality analgesia. CNS Spectr. (2006) 11:45–51. 10.1017/S1092852900024202

14. Xu G, Zhang M, Wang Y, Liu Z, Huo C, Li Z, et al. Functional connectivity analysis of distracted drivers based on the wavelet phase coherence of functional near-infrared spectroscopy signals.PLoS One. (2017) 12:e0188329. 10.1371/journal.pone.0188329

15. Xu J, Liu X, Zhang J, Li Z, Wang X, Fang F, et al. FC-NIRS: a functional connectivity analysis tool for near-infrared spectroscopy data. Biomed Res Int. (2015) 2015:248724. 10.1155/2015/248724

16. Baliki MN, Mansour AR, Baria AT, Apkarian AV. Functional reorganization of the default mode network across chronic pain conditions.PLoS One. (2014) 9(9): e106133. 10.1371/journal.pone.0106133

17. Hashmi JA, Baria AT, Baliki MN, Huang L, Schnitzer TJ, Apkarian AV. Brain networks predicting placebo analgesia in a clinical trial for chronic back pain. Pain. (2012) 153:2393–402. 10.1016/j.pain.2012.08.008

18. Baliki MN, Apkarian AV. Nociception, pain, negative moods, and behavior selection. Neuron. (2015) 87:474–91. 10.1016/j.neuron.2015.06.005

19. Erpelding N, Davis KD. Neural underpinnings of behavioural strategies that prioritize either cognitive task performance or pain. Pain. (2013) 154:2060–71. 10.1016/j.pain.2013.06.030

20. Sun VC-Y, Borneman T, Ferrell B, Piper B, Koczywas M, Choi K. Overcoming barriers to cancer pain management: an institutional change model. J Pain Symptom Manage. (2007) 34:359–69. 10.1016/j.jpainsymman.2006.12.011

21. Stokefarm Productions. Oceania VR. Directed by James Donald. Available online at: https://journeymanvr.squarespace.com/oceaniavr (Accessed June 29, 2026).

22. Santosa H, Zhai X, Fishburn F, Huppert T. The NIRS brain AnalyzIR toolbox. Algorithms. (2018) 11:73. 10.3390/a11050073

23. Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The faces pain scale–revised: toward a common metric in pediatric pain measurement. Pain. (2001) 93:173–83. 10.1016/S0304-3959(01)00314-1

24. Deng X, Jian C, Yang Q, Jiang N, Huang Z, Zhao S. The analgesic effect of different interactive modes of virtual reality: a prospective functional near-infrared spectroscopy (fNIRS) study. Front Neurosci. (2022) 16:1033155. 10.3389/fnins.2022.1033155

25. Gao L, Lin Q, Tian D, Zhu S, Tai X. Advances and trends in the application of functional near-infrared spectroscopy for pediatric assessments: a bibliometric analysis. Front Neurol. (2024) 15:1459214. 10.3389/fneur.2024.1459214

26. Hu X-S, Nascimento TD, Da Silva AF. Shedding light on pain for the clinic: a comprehensive review of using functional near-infrared spectroscopy to monitor its process in the brain. Pain. (2021) 162:2805–20. 10.1097/j.pain.0000000000002293

27. Farrar JT, Young Jr JP, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. (2001) 94:149–58. 10.1016/S0304-3959(01)00349-9

28. Bennett MI, Rayment C, Hjermstad M, Aass N, Caraceni A, Kaasa S. Prevalence and aetiology of neuropathic pain in cancer patients: a systematic review. Pain. (2012) 153:359–65. 10.1016/j.pain.2011.10.028

29. Treede R-D, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, et al. A classification of chronic pain for ICD-11. Pain. (2015) 156:1003–7. 10.1097/j.pain.0000000000000160

30. Fiúza-Fernandes J, Pereira-Mendes J, Esteves M, Radua J, Picó-Pérez M, Leite-Almeida H. Common neural correlates of chronic pain–A systematic review and meta-analysis of resting-state fMRI studies. Prog Neuropsychopharmacol Biol Psychiatry. (2025) 138:111326. 10.1016/j.pnpbp.2025.111326

31. Ueno K, Oshiro Y, Kan S, Nomura Y, Satou H, Obata N, et al. Resting-state brain functional connectivity in patients with chronic intractable pain who respond to spinal cord stimulation therapy. Br J Anaesth. (2025) 134:492–500. 10.1016/j.bja.2024.10.011

32. Baliki MN, Geha PY, Apkarian AV, Chialvo DR. Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics. J Neurosci. (2008) 28:1398–403. 10.1523/JNEUROSCI.4123-07.2008

33. Ong W-Y, Stohler CS, Herr DR. Role of the prefrontal cortex in pain processing. Mol Neurobiol. (2019) 56:1137–66. 10.1007/s12035-018-1130-9

34. Tumati S, Martens S, de Jong BM, Aleman A. Lateral parietal cortex in the generation of behavior: implications for apathy. Prog Neurobiol. (2019) 175:20–34. 10.1016/j.pneurobio.2018.12.003

35. Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. Prog Neurobiol. (2009) 87:81–97. 10.1016/j.pneurobio.2008.09.018

36. Ochsner KN, Gross JJ. The cognitive control of emotion. Trends Cogn Sci. (2005) 9:242–9. 10.1016/j.tics.2005.03.010

37. Johansson E, Xiong H-Y, Polli A, Coppieters I, Nijs J. Towards a real-life understanding of the altered functional behaviour of the default mode and salience network in chronic pain: are people with chronic pain overthinking the meaning of their pain? J Clin Med. (2024) 13:1645. 10.3390/jcm13061645

38. Keefe FJ, Huling DA, Coggins MJ, Keefe DF, Rosenthal ZM, Herr NR, et al. Virtual reality for persistent pain: a new direction for behavioral pain management. Pain. (2012) 153:2163–6. 10.1016/j.pain.2012.05.030

39. Nagamine T. Application of virtual reality technology improves the functionality of brain networks in individuals experiencing pain. World J Clin Cases. (2025) 13:97856. 10.12998/wjcc.v13.i3.97856

40. Nagamine T. Challenges in using virtual reality technology for pain relief. World J Clin Cases. (2025) 13:103372. 10.12998/wjcc.v13.i16.103372

41. Jalon I, Berger A, Shofty B, Goldway N, Artzi M, Gurevitch G, et al. Lesions to both somatic and affective pain pathways lead to decreased salience network connectivity. Brain. (2023) 146:2153–62. 10.1093/brain/awac403

42. Li A, Montaño Z, Chen VJ, Gold JI. Virtual reality and pain management: current trends and future directions. Pain Manag. (2011) 1:147–57. 10.2217/pmt.10.15

Associated Data

Data Availability Statement

The data that support the findings of this study are available from the corresponding author [SBS] upon reasonable request.