Neural Correlates of Hypoalgesia Driven by Observation

Pain Clinical Trial

Official title:

Neural Correlates of Hypoalgesia Driven by Observation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03897998
• Other study ID #: HP-00085382
• Status: Recruiting
• Phase: Phase 2
• Start date: November 1, 2021
• Est. completion date: July 30, 2024

Study information

• Verified date: September 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

Placebo effects held an ambivalent place in health care for at least two centuries. On the one hand, placebos are traditionally used as controls in clinical trials to correct for biases and the placebo response is viewed as an effect to be factored out in order to isolate and accurately measure the effects of the treatment. On the other hand, there is scientific evidence that placebo effects represent fascinating psychoneurobiological events involving the contribution of distinct central nervous as well as peripheral physiological mechanisms that influence pain perception and clinical pain symptoms and substantially modulate the response to pain therapeutics. Therefore, placebo effects have shifted from being a challenge for clinical trials to a resource to trigger the reduction of pain based on endogenous mechanisms that can be activated in the brain to promote hypolagesia, self-healing, and well-being. This is relevant in acute pain settings given that chronic opioid users die within approximately 2.5 years of being prescribed their first opioid medication to treat acute pain.

The overall hypothesis is that observational learning influences neural pain modulation and cognition systems, including processes associated with mentalizing (the ability to cognitively understand mental states of others), empathy (the ability to share an emotional experience), and expectancy (the anticipation of a benefit). The objective is to determine the brain mechanisms of observationally-induced analgesia using brain mapping approaches that target changes in blood oxygenation and oscillatory activity in the brain, thus enabling investigators to draw inferences about the localization and extent of neurobiological activation underlying hypoalgesia driven by observation. Therefore, the investigators designed innovative experiments using pharmacological fMRI, EEG, and combined EEG-fMRI measurements.

Description:

Analgesic effects can also occur without formal conditioning and direct prior experience because crucial information necessary to build up expectations of analgesia can be acquired through observation of a therapeutic benefit in others. Placebo analgesic effects following the observation of a benefit in another person are similar in magnitude to those induced by directly experiencing an analgesic benefit. These observations emphasize that contextual cues substantially modulate the individual placebo analgesic effects.

In this project, the investigators propose a compelling research agenda to explore the neural mechanisms of hypoalgesia driven by observation as a foundation for future development of novel nonpharmacological pain therapies using pharmacological functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and combined EEG/fMRI. It builds on a decade of experience in placebo research in PI Colloca's lab and with University of Maryland collaborators experienced in brain mapping and pain research. In Aim 1, the investigators will determine the role of endogenous opioids on the neural mechanisms of observationally-induced hypoalgesia by using the opioid antagonist naloxone in a functional Magnetic Resonance Imaging (fMRI) setting. In Aim 2, the investigators will identify the impact of empathy by exploring how being in the immersive environment can enhance observationally-induced analgesia. In Aim 3, the investigators will leverage the EEG/fMRI to determine the neural EEG/fMRI transient changes that could co-occur when socially-induced expectations are violated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 182
• Est. completion date: July 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Age (18-55 years old)

• English speaker (written and spoken)

Exclusion Criteria:

• Cardiovascular, neurological diseases, pulmonary abnormalities, kidney disease, liver disease, degenerative neuromuscular disease, or history of cancer within past 3 years

• Any history of chronic pain disorder or currently in pain

• Severe psychiatric condition (e.g. schizophrenia, bipolar disorders, mania, autism) and /or psychiatric condition leading to treatment and/or hospitalization within the last 3 years.

• Personal history of mania, schizophrenia, or other psychoses

• Nasal Polyps

• Chronic intranasal drug use ( e.g., intranasal decongestants; antihistamines)

• Lifetime alcohol/drug dependence, or alcohol/drug abuse in past 3 months

• Use of antidepressants, ADHD medication, non-over-the-counter painkillers, methadone, benzodiazepines, barbiturates, and/or narcotics during the past 3 months

• Pregnancy or breast feeding

• Color-blindness

• Impaired, uncorrected hearing

• Left handed

• Allergies or sensitivities to creams, lotions, or food coloring

• Any non-organic implant or any non-removable metal device (e.g., pacemaker, cochlear implants, stents, surgical clips, non-removable piercings)

• Any prior eye injury or the potential of a foreign body in the eye (e.g., worked in metal fields)

• Persistent functional impairment due to a head trauma

• Fear of closed spaces

• Any other contraindications for MRI (e.g., large tattoos on head and neck)

• Previously participated in other "Pain Perception in the Brain" Studies in Colloca lab Failed drug test (testing for opiates, cocaine, methamphetamines, amphetamines, and THC)

Related Conditions & MeSH terms

• Pain
• Placebo
• Virtual Reality

Intervention

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.

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (3)

Benedetti F, Pollo A, Colloca L. Opioid-mediated placebo responses boost pain endurance and physical performance: is it doping in sport competitions? J Neurosci. 2007 Oct 31;27(44):11934-9. doi: 10.1523/JNEUROSCI.3330-07.2007. — 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

Schenk LA, Krimmel SR, Colloca L. Observe to get pain relief: current evidence and potential mechanisms of socially learned pain modulation. Pain. 2017 Nov;158(11):2077-2081. doi: 10.1097/j.pain.0000000000000943. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neural responses	Blood oxygenation level dependent (BOLD) responses will allow the identification of relative activation/deactivation in the brain as result of events (e.g. painful stimulations) that will be given during the experiment and the treatment administration.	Two days
Secondary	Pain ratings	Participants will rate painful and non-painful stimulations on a Visual Analogue Scale raging from 0=no pain to 100= maximum unbearable pain.	Two days