Virtual Reality and Cranial Nerve Neuromodulation to Manage Chronic Pain

In Canada, many veterans suffer from chronic pain, with a prevalence twice as high as that of the general population. Chronic pain is often linked to post-traumatic stress disorder(PTSD). Together, these two conditions impact on the functioning and quality of life of veterans. Recent studies suggest that the autonomic nervous system (ANS) plays a central role in the pathophysiology of chronic pain and PTSD, making it a prime therapeutic target.

Virtual reality (VR) is already being used with veterans, and its effectiveness in relieving pain and PTSD is well documented in veterans, notably by modulating ANS reactivity. Two types of VR approaches are commonly used: VR with prolonged exposure (desensitization) and VR with a calming effect (aimed at normalizing the stress response and SNA reactivity).The latter is better tolerated than prolonged-exposure VR and remains better suited to rebalancing ANS reactivity and relieving symptoms. It calms the ANS and relieves pain (acute and chronic) when combined with traditional rehabilitation, but its effects on pain intensity remain modest and limited in time.

To optimize the benefits of VR, it is proposed to combine VR with a non-pharmacological method, as suggested by experts. This non-pharmacological approach is cranial nerve non-invasive neuromodulation (CN-NINM). CN-NINM is an innovative approach that stimulates the cranial nerves via electrodes placed directly on the tongue; the impulses reach and modulate the activity of ANS structures located in the brainstem. These structures are linked to autonomic functions and pain modulation. This combination could reinforce and prolong the positive effects of VR on veterans' pain.

Objectives: 1) To document the effect of VR (an intervention currently provided) on pain and ANS reactivity in veterans with PTSD, 2) to assess the ability of CN-NINM (vs sham CN-NINM) to potentiate the effects of VR on pain and on ANS reactivity.

Methods: In this within-subjects factorial crossover design, 15 veterans will be recruited. Sociodemographic, pain and PTSD-related variables will be collected to confirm participant eligibility. Prior to the interventions, participants will undergo an assessment of both clinical pain (intensity and unpleasantness of pain, numerical scale 0-10) and experimental pain. The tonic thermal experimental pain paradigm involves the application of a thermode (hotplate) to participants' forearms. Thermal nociceptive stimuli will be induced for 2 minutes on the participants' forearm using the thermode. Although the temperature remains constant for the entire 2 minutes, the participant will be informed that the temperature may increase, decrease, or remain stable during the procedure. The participant will then, at all times, evaluate the intensity of the pain with a visual analogue scale connected to a computer(CoVAS: visual analogue scale from 0 to 100).

Additionally, participants will complete clinical questionnaires assessing anxiety, pain and PTSD-related symptoms. Various autonomic measures (blood pressure, heart rate reactivity \[HRV\], electrodermal response) will also be taken to characterize ANS reactivity before and after each intervention. Participants will receive the 3 interventions (VR, VR+CN-NINM and VR+ sham CN-NINM) randomly assigned. The VR headset will broadcast calming images for 20 minutes. CN-NINM will be applied, using a portable stimulator, placed directly on the tongue of the participants for 20 minutes simultaneously with VR.

• Change in pain intensity on the CoVAS [Срок оценки: The assessments will be done at the baseline and just after the 20 minutes of application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo).]
• Change in measures of blood pressure [Срок оценки: The assessments will be done at baseline, during the 20 min application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo) and just after the 20 min application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo).]
• Change in heart rate variability [Срок оценки: The assessments will be done at the baseline, during the 20 minutes of application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo) and just after the 20 minutes of applications of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo).]
• Change in electrodermal response [Срок оценки: The assessments will be done at the baseline, during the 20 min application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo) and just after the 20 min application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo).]
• Change in pain intensity and impact on physical function using the Brief Pain Inventory (BPI) [Срок оценки: The questionnaire will be done at the baseline (T0), beginning and just after the 20 minutes of application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo) and one week after the last intervention.]
• Change in the qualitative aspect of pain with the McGill Pain Questionnaire (MPQ) [Срок оценки: The questionnaire will be done at the baseline (T0), beginning and just after the 20 min application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo) and one week after the last intervention.]
• Change in pain-related disability using the Pain Disability Questionnaire (PDQ) [Срок оценки: The questionnaire will be done at the baseline (T0), beginning and just after the 20 min application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo) and one week after the last intervention.]
• Change in State-Trait Anxiety using the The State-Trait Anxiety Inventory (STAI) [Срок оценки: The questionnaire will be done at the baseline (T0), beginning and just after the 20 minutes of application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo) and one week after the last intervention.]
• Change in Patient Global Impression of Change (PGIC) [Срок оценки: The questionnaire will be done at the baseline (T0), beginning and just after the 20 minutes of application of each intervention (VR, VR + CN-NINM, VR+CN-NINM placebo) and one week after the last intervention.]