Neural Mechanisms of Immersive Virtual Reality in Chronic Pain

Pain Clinical Trial

Official title:

Neural Mechanisms of Immersive Virtual Reality in Chronic Pain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04851301
• Other study ID #: HP-00095888
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 1, 2021
• Est. completion date: November 30, 2027

Study information

• Verified date: May 2023
• Source: University of Maryland, Baltimore
• Contact: Research Coordinator
• Phone: 410-706-5975
• Email: NRSCollocaLab[@]umaryland.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 259
• Est. completion date: November 30, 2027
• Est. primary completion date: October 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 88 Years

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Pain
• Pain
• Placebo
• Temporomandibular Disorder
• Temporomandibular Joint Disorders
• Temporomandibular Joint Dysfunction Syndrome
• Virtual Reality

Intervention

Behavioral:
• Active Virtual Reality
Participants will be assigned to an immersive VR environment.
• sham Virtual Reality
Participants will be assigned to a sham VR environment without the immersive experience.

Other:
• No Intervention
Participants will experience tonic pain tolerance tests without exposure to any environments.

Drug:
• Naloxone
4mg of Naloxone will be administered (0.1 mL of 40 mg/ml naloxone solution given intranasally). A random allocation sequence will be independently generated by the UM Pharmacy. The Principal investigator will call for each experiment.

Other:
• Saline
Intranasal Normal Saline (0.1 mL 0.9% sodium chloride) will be administered shortly before beginning the fMRI experiment. A random allocation sequence will be independently generated by the UM Pharmacy. The Principal investigator will call for each experiment.
• Natural history
Participants will not be provided Naloxone or Saline.

Locations

Country	Name	City	State
United States	Luana Colloca	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ischemic pain endurance	Increments in experimental ischemic pain endurance will be assessed using a timer (minutes of tolerance)	one session lasting from 2 to 3 hours
Secondary	Ischemic pain rating	Increments in experimental ischemic pain endurance will be assessed using Visual Analogue Scale (VAS) (self-reported numbers) anchored from 0=no pain to 100=maximum tolerable pain. The VAS will be used every 10 seconds during the ischemic pain endurance task	one session lasting from 2 to 3 hours