Background & Aims

Exposure to natural environments have demonstrated analgesic efficacy for chronic pain[1]. However, the underpinning mechanisms remain unclear, hindering the development of tailored therapies. Investigating the effects of nature immersion proves challenging, due to logistical complexities and a lack of control over the environment. Virtual reality (VR) can address this by offering immersive experiences with complete experimental control. It also allows for concurrent measurements, helping to disentangle the neurophysiological mechanisms involved. Accordingly, this study assessed the impact of VR-delivered nature scenes on responses to high-frequency stimulation (HFS), a neuropathic pain surrogate model[2], in healthy participants. To explore mechanistic underpinnings of analgesic effects, functional magnetic resonance imaging (fMRI), psychometrics, descending pain modulation markers and nociceptive withdrawal reflex (NWR)[3] endpoints were collected in the same individuals.

Methods

19 participants (11 females, mean (SD) = 31(10), expected final sample N = 30) attended five visits. In visits 1-3 (i.e., ‘baseline’, ‘VR’, ‘sham’), participants’ mechanical pain sensitivity (MPS)[4] scores and pain perception mapping to pinprick stimulation were calculated in both forearms at prior as well as 15min, 35min and 50min post HFS (right side only). The VR and sham sessions included, for 45mins post HFS, immersion in a VR-nature scene or viewing a 2D nature scene, respectively. Visit 4 included resting state fMRI assessments before, during and following tonic pain stimulation. Visit 5 included NWR measurements at baseline, and during VR immersion in both a nature scene and an urban scene as control. Percentage of change from pre HFS in MPS scores within and across sessions 1-3 were compared via repeated measures analyses of variance (ANOVA) and pain mappings were plotted. Prospectively, relationships between fMRI assessments and NWR data with MPS results will be calculated.

Results

For the test arm, main ANOVA showed significant effects of visit (F=4.85, p=0.041), testing minutes (F=11.59, p=0.003) and a tendency to significance for the interaction F=4.85, p=0.08). Post-hoc pairwise comparisons showed that MPS significantly increased following HFS in the baseline condition, but not in the VR or sham conditions. For the control arm, there was a significant effect of visit (F=4.88, p=0.040), which corresponded to significantly lower MPS in the VR and sham conditions compared to baseline 15min post HFS. Percentage of change plots for pain mappings showed that on the baseline session, HFS induced heterotopic sensitisation that peaked at 35mins post HFS. During the VR condition, the extent of heterotopic sensitisation following HFS was reduced proximally across all measures, and this reduction was further observed in the sham condition, also in the distal direction.

Conclusions

Our empirical findings thus far indicate that the presentation of nature stimuli via VR and a 2D screen mitigates the pain sensitisation effects associated with HFS. Notably, these effects manifest in different manners and to varying degrees between the VR and sham sessions. This implies the potential existence of distinct mechanisms underlying these behavioural results. Via the utilisation of psychometric assessments, fMRI, and NWR measures in our study, and through the use of regression and dynamic causal modelling approaches, we will shed light on the interplay of factors contributing to the observed differences between VR and sham VR, thereby offering a more comprehensive understanding of the underlying mechanisms at play in the context of nature-based therapy delivered with or without VR technology.

References

1.Lee, M.J., et al., The effect of nature exposure on pain experience and quality of life in patients with chronic pain: A systematic review and meta-analysis protocol. PLoS One, 2023. 18(9): p. e0291053.
2.Fawsitt-Jones, H., et al., Reliability of quantitative sensory testing in the assessment of somatosensory function after high-frequency stimulation–induced sensitisation of central nociceptive pathways. Pain, 2022: p. 10.1097.
3.Defrin, R., et al., Differential effect of supraspinal modulation on the nociceptive withdrawal reflex and pain sensation. Clinical neurophysiology, 2007. 118(2): p. 427-437.
4.Georgopoulos, V., et al., Quantitative Sensory Testing (QST) and predicting outcomes for musculoskeletal pain, disability and negative affect: a systematic review and meta-analysis. Pain, 2019. 160(9): p. 1920.

Presenting Author

Sonia Medina

Poster Authors

Sonia Medina

MD, PhD

University of Exeter

Lead Author

Sophie Clarke

University of Exeter

Lead Author

Sam Hughes

University of Exeter

Lead Author

Topics

  • Pain Imaging