Background & Aims

The experience of pain contains a nociceptive component and an affective component; the latter being inherently subjective and dependent on factors such as emotion, mood, time of day, and stress. It was previously shown that the Virtual Reality PainCart (VR-PainCart), can be used to modulate the pain experience and thus function as a biomarker for the affective component of pain in healthy volunteers. Diazepam is a drug of the benzodiazepine family used to treat a range of conditions, including anxiety, and may influence this affective component of pain. Our hypothesis is that the VR-PainCart can be used to assess the effect of drugs on the affective component of pain in healthy subjects.

Methods

In this randomized crossover study in 24 healthy male participants, we assessed the effect of a simulated wound in VR on the electrical pain detection (PDT) and tolerance (PTT) thresholds during the electrical stair test. Participants had two rounds of pre-dose tests, followed by administration of 5 mg diazepam or placebo, and six rounds of post-dose tests at different time points following study drug administration. Each round of testing consisted of an electrical pain test, followed by two VR conditions in alternating order: (1) VR-wound: a burn-wound, smoke, and electrical sparks become visible and audible with increasing stimulus intensity, and (2) VR-neutral: no additional aspects. The VR simulation presented a copy of the research room from first person view. The PDT and PTT were recorded during both VR conditions and outside of VR. VAS-Questionnaires assessed pain intensity and unpleasantness, and the McGill Pain Questionnaire (MPQ) was used to investigate pain characteristics.

Results

The PDT increased with participants using diazepam compared to placebo when seeing the VR-wound (Estimated Difference (ED): 6.0%, CI 2.4 – 53.2, p<0.05). Although a trend was seen in the PTT in VR-wound, where diazepam induced a higher PTT when compared to placebo, this difference did not reach statistical significance(ED: 6.5%, CI -3.1 – 17.0%, p=0.179). Pain intensity after diazepam compared to placebo was lower, however, the difference did not reach statistical significance (-0.5% CI -3.3 – 2.3, p=0.732). For the experienced unpleasantness the difference between placebo and diazepam remained unchanged (ED: 0.8%, CI -2.5 – 4.1, p=0.861), as was the case for MPQ(ED: 0.04%, CI -0.04 – 0.13, p=0.328).

Conclusions

We showed that a VR simulated wound induced an enhanced pain perception when added to an electrical nociceptive task in healthy subjects. The administration of diazepam increased the PDT in the VR-wound environment, demonstrating that the affective component of pain, added to a nociceptive stimulus, can be pharmacologically modulated. Contrarily, we did not detect a significant difference in subjective pain experience with the pain questionnaires. Future research using the VR-PainCart methodology will include expansion of the study population to include women and patients experiencing other types of pain or altered affective states such as patients with depression and/or anxiety. Similarly, drugs targeting the affective component such as antidepressants may be investigated. We aim to use the VR-PainCart to evaluate the effects of new analgesic compounds that are expected to decrease pain through their influence on the affective component of pain.

References

None

Presenting Author

Koen Rietdijk

Poster Authors

Ingrid Koopmans

MSc

Centre for Human Drug Research

Lead Author

Koen Rietdijk MD

MPH

Centre for Human Drug Research

Lead Author

Roman Bohoslavsky

MSc

Centre for Human Drug Research

Lead Author

Robert-Jan Doll

PhD

Centre for Human Drug Research

Lead Author

Geert Jan Groeneveld MD PhD

Centre for Human Drug Research

Lead Author

Topics

  • Assessment and Diagnosis