Clinical trial NCT04851301: Neural Mechanisms of Immersive Virtual Reality in Chronic Pain
Official title: Neural Mechanisms of Immersive Virtual Reality in Chronic Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pain
Virtual Reality
Placebo
Temporomandibular Disorder
Keywords: Naloxone
Observation
TMD volunteers
VR
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2021-04-20
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Maximum age (years): 88
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: AIM 1: This is a double-blinded, randomized, between- and within-subjects design (3 X 3) with TMD participants randomly assigned to one of three groups. The three groups are 1. Naloxone group 2. Saline group 3. Natural history group, in which participants will not be given any drugs. Within-subjects factor: All three groups will go through the following 3 conditions:1. Active VR (theBlu); 2. Sham VR; 3. No-VR.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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. Investigator will determine the role of the opioid tone (AIM1). In Aim 1, the investigators will determine the role of the endogenous opioid tone for VR-induced hypoalgesia in TMD participants using VR, tonic painful stimuli, and naloxone given intranasally with established mu-opioid receptor occupancy to determine how the opioid tone shapes VR-induced hypoalgesia.

Eligibility criteria: Inclusion Criteria:

* Age (18-88 years)
* English speaker (written and spoken)
* Temporal Mandibular Disorder (TMD) for at least 3 months

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 other than TMD related (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 antidepressants, ADHD medication, non-over-the-counter painkillers, methadone, benzodiazepines, barbiturates, and/or narcotics during the past 3 months
* Lifetime alcohol/drug dependence or alcohol/drug abuse in the past 3 months
* Pregnancy or breastfeeding
* Color-blindness
* Pain in jaw or temple in last 3 months due to toothache or infection
* Any facial trauma that has occurred in the last 6 weeks
* History of severe facial trauma in the last 3 months
* Impaired or uncorrected hearing
* Conditions that would interfere with the VR mask placement (e.g. trauma, burn, infection)
* Known history of severe motion sickness
* High blood pressure or symptomatic low blood pressure
* History of fainting
* History of angioedema
* Failed drug test (testing for opiates, cocaine, methamphetamines, amphetamines, and THC)

Primary outcomes:
measure: Ischemic pain endurance
timeFrame: one session lasting from 2 to 3 hours
Secondary outcomes:
measure: Ischemic pain rating
timeFrame: one session lasting from 2 to 3 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Luana Colloca
state: Maryland
Study officials:
affiliation: University of Maryland Baltimore School of Nursing
name: Luana Colloca, MD/PhD/MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.