Effects of Anticipation of Pain Relief on Brain Mechanisms

Neurochemical Mediation of Placebo Responses in Humans

This study will use brain imaging technology to examine chemical systems in the brain that suppress pain and stress when an individual has an expectation of pain relief.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Procedure: Hypertonic saline; Procedure: Isotonic saline

Detailed Description

Evidence suggests that the expectation of pain relief, even if a person receives only a placebo, can provide actual therapeutic benefits. The µ-opioid receptor system, located in the brain, is activated during anticipation of pain relief; this activation suppresses stress and pain responses. This study will use brain imaging technology to examine the effects of a placebo intervention on µ-opioid neurotransmitters. Examination of the factors that regulate these placebo-activated neurotransmitter responses will clarify the overall neurobiology underlying variations in the responses to placebos, as well as pain and other stressful conditions, ultimately leading to the optimization of medical and psychological interventions.

This study will last several hours during one study visit. Participants will receive both a painful and a painless injection while undergoing positron emission tomography (PET) brain imaging. The painful injection will consist of small amounts of hypertoninc saline (concentrated saline that causes cell shrinkage) in the jaw muscle over a 20-minute period. Several minutes after participants receive hypertonic saline, they will receive an injection with isotonic saline not associated with pain in the opposite jaw muscle. After participants receive the injections, they will either be told or not be told about a pain relief intervention. PET imaging will continue as participants either anticipate or do not anticipate pain relief. Participants will be asked about their pain levels repeatedly throughout the study; their responses will be entered into a computer-controlled system which will modulate rates of saline infusion.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to comply with all study requirements

Exclusion Criteria:

• Presence of pain at study entry
• Personal or first-degree (e.g., mother, father, sister, brother) family history of neurologic or psychiatric disorders
• History of substance abuse or dependence
• Left-handed or ambidextrous
• Positive urine toxicology screen
• Acute or uncorrected medical illness that may interfere with the study
• Unable to tolerate brain scanning procedures
• Current treatment with antipsychotics, mood stabilizers, isoniazid (a drug for tuberculosis [TB]), glucocorticoids/mineralocorticoids, psychostimulant appetite suppressants, or centrally active antihypertensive drugs
• Treatment with hormones, antidepressants, or opioids within 6 months prior to study entry
• Treatment with sedative hypnotic medications or over-the-counter sleeping aids within 1 month prior to study entry
• Diagnosis of depression
• Competitive exercise, or exercise exceeding 1 hour each day
• Regular smoking within 5 years prior to study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: pain challenge	Procedure: Hypertonic saline; To elicit pain; Procedure: Isotonic saline; Non-painful control
Sham Comparator: non-painful control	Procedure: Hypertonic saline; To elicit pain; Procedure: Isotonic saline; Non-painful control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Placebo-induced activation of brain opioid neurotransmission	90 min

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Jon-Kar Zubieta, MD, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Actual): March 24, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Stress; Analgesia; Positron-Emission Tomography; Pain Relief; Endorphins; Opioid Receptors
• Other Study ID Numbers: R01AT001415-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No