Neural Mechanisms of Immersive Virtual Reality in Chronic Pain (VR TMD EEG) (VR TMD EEG)

Neural Mechanisms of Immersive Virtual Reality in Chronic Pain

This project examines, in chronic pain, the mechanisms of immersive virtual reality compared to the mechanisms of placebo hypoalgesia. The potential of developing new non-pharmacological premises for low-risk interventions for pain management is high.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain; Virtual Reality; Temporomandibular Disorder; Placebo
• Intervention / Treatment: Device: RelieVRx; Device: Sham-VR; Other: No-VR (natural history control)

Detailed Description

Virtual reality (VR) has been seen as an intervention for alleviating clinical chronic (and acute) pain. An approach to pain management utilizing VR presents opportunities for reducing pain and suffering by using immersive, aesthetic, and multisensory stimulation. Investigator will analyze the behavioral and neural mechanisms of active VR against sham VR as two methods that investigate descending pain modulation. Thus, the central hypothesis is that those who respond to placebos will likely respond to active VR. If VR-induced analgesia depends upon the release of endogenous opioids.

In this project, the investigators will determine the effects of VR at the neural and clinical levels directly for TMD participants, inviting participants from an existing Colloca Lab-based cohort phenotyped for diagnosis, grade, and low/high impact pain profiles and prospective TMD participants in collaboration with Johns Hopkins University. These participants have agreed to be recontacted for further research.

In this study, based on our PAF study and modulation of autonomic measurements via VR, we will determine the role of acute and 3-week VR intervention to help restore PAF oscillations to normal. PAF and autonomic measurements will be collected in TMD participants characterized by low/high-impact pain. All participants will go through Active VR, Sham VR and NH phases (3-week each) where participants will be monitored for changes in cortical excitability via PAF oscillations and clinical benefit via EMA.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Research Coordinator; Phone Number: 410-706-5975; Email: NRSCollocaLab@umaryland.edu
• Study Contact Backup: Name: Katia Matychak, MS; Phone Number: 410-706-5975; Email: katiamatychak@umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201-1512
      • University of Maryland
      • Contact: Luana Colloca, MD, PhD, MS; Phone Number: 301-364-8089; Email: colloca@umaryland.edu
      • Contact: Katia Matychak, MS; Phone Number: 4107065975; Email: asuhr@umaryland.edu
    • Baltimore, Maryland, United States, 21201-1512
      • Luana Colloca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age (18-88 years)
• English speaker (written and spoken)
• Temporal Mandibular Disorder (TMD) for at least 3 months
• TMD Grade Chronic Pain Scale (GCPS) ≥ 0

Exclusion Criteria:

• Present or past degenerative neuromuscular disease
• Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, history of cancer within past 3 years
• Cervical pain (e.g. stenosis, radiculopathy)
• Any personal (or family first degree) history of mania, schizophrenia, or other psychoses
• Severe psychiatric condition (e.g. schizophrenia, bipolar disorders, autism) leading to hospitalization within the last 3 years.
• Use of Antipsychotics (e.g., Risperdal, Ability and clozaril)Lifetime alcohol/drug dependence or alcohol/drug abuse in past 3 months
• Pregnancy or breast feeding
• Color-blindness
• Impaired or uncorrected hearing
• Non-dominant hand
• Any facial trauma that has occurred in the last 6 weeks
• History of a severe facial trauma in the last 2-3 months
• Conditions that would interfere with the VR mask placement (e.g. trauma, burn, infection)
• Known history of severe motion sickness
• Non-removable head cover, artificial hair, certain types of braids or dreadlocks
• History of fainting
• History of angioedema
• Failed drug test (testing for opiates, cocaine, methamphetamines, and amphetamines)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: High impact TMD; Other: TMD Phenotype TMD participants will be clinically phenotyped into two between-subject groups based on their score on the Graded Chronic Pain Scale (GCPS). This group will have a GCPS grade 2b, 3, and 4.	Device: RelieVRx; Participants will use RelieVRx daily for 20min/day for 3 weeks; Other Names: Active-VR; Device: Sham-VR; Participants will use Sham-VR, consisting of video, images, and sound in a head-mounted display but lack the "sense of presence" and immersive features of Active-VR (for example, scene changes with head movement). Participants will use the Sham-VR daily for 20min/day for 3 weeks; Other: No-VR (natural history control); Participants will continue regular/usual care without any VR devices (goggles or audiovisual input)
Other: Low impact TMD; Other: TMD Phenotype TMD participants will be clinically phenotyped into two between-subject groups based on their score on the Graded Chronic Pain Scale (GCPS). This group will have a GCPS grade 0, 1, and 2a	Device: RelieVRx; Participants will use RelieVRx daily for 20min/day for 3 weeks; Other Names: Active-VR; Device: Sham-VR; Participants will use Sham-VR, consisting of video, images, and sound in a head-mounted display but lack the "sense of presence" and immersive features of Active-VR (for example, scene changes with head movement). Participants will use the Sham-VR daily for 20min/day for 3 weeks; Other: No-VR (natural history control); Participants will continue regular/usual care without any VR devices (goggles or audiovisual input)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak alpha frequency (PAF)	EEG response PAF when participants are undergoing the in-person VR	We will acquire 2-10 min of baseline EEG with open eyes and 2-10 min of EEG with closed eyes. This measurement will occur at each of the four in-person visit approximately every 3 weeks.
Objective incremental Celsius changes in heat-pain tolerance	Heat pain tolerance to incremental change in temperature will be obtained using a timer (minutes of tolerance)	The heat incremental changes range from 30 sec to 2 min tolerance. This measurement will occur at each of the four in-person visit approximately every 3 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective VAS (Visual Analog Scale) scores for mood, situational anxiety, and pain intensity/unpleasantness	Participants will take Ecological Momentary Assessment questionnaires. Minimum Value: 0 Maximum Value: 100 Score interpretation: 0=not at all, 100=most/strongest For example, anxiety on a scale of 0-100, 0=no anxiety, 100=the most anxious	Daily during the 3-week condition timeframe

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Publications and helpful links

General Publications

• Colloca L. The Placebo Effect in Pain Therapies. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:191-211. doi: 10.1146/annurev-pharmtox-010818-021542. Epub 2018 Sep 14.
• Honzel E, Murthi S, Brawn-Cinani B, Colloca G, Kier C, Varshney A, Colloca L. Virtual reality, music, and pain: developing the premise for an interdisciplinary approach to pain management. Pain. 2019 Sep;160(9):1909-1919. doi: 10.1097/j.pain.0000000000001539. No abstract available.
• Colloca L, Raghuraman N, Wang Y, Akintola T, Brawn-Cinani B, Colloca G, Kier C, Varshney A, Murthi S. Virtual reality: physiological and behavioral mechanisms to increase individual pain tolerance limits. Pain. 2020 Sep 1;161(9):2010-2021. doi: 10.1097/j.pain.0000000000001900.
• Amanzio M, Benedetti F. Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci. 1999 Jan 1;19(1):484-94. doi: 10.1523/JNEUROSCI.19-01-00484.1999.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ecological Momentary Assessment; VR; Clinical Pain; TMD volunteers
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Stomatognathic Diseases; Jaw Diseases; Craniomandibular Disorders; Mandibular Diseases; Myofascial Pain Syndromes; Chronic Pain; Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome
• Other Study ID Numbers: HP-00095888 (VR TMD EEG)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At this time, there is neither intent nor plan to share IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes