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.

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.

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)

At this time, there is neither intent nor plan to share IPD.

The UM Pharmacy will assign de-identified study IDs to participants and provide the study drug (Naloxone or Saline) so that participants, the person conducting the experiment, and the investigator will be blind to the participant's group.