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Effects of Anticipation of Pain Relief on Brain Mechanisms

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00200876
Recruitment Status : Completed
First Posted : September 20, 2005
Last Update Posted : March 24, 2017
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Jon-Kar Zubieta, University of Michigan

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pain Procedure: Hypertonic saline Procedure: Isotonic saline Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Hypertonic saline is a challenge to activate endogenous opioid systems as assessed with positron emission tomography. There is no treatment involved. Isotonic saline is the control.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Neurochemical Mediation of Placebo Responses in Humans
Study Start Date : September 2003
Actual Primary Completion Date : February 2008
Actual Study Completion Date : June 2008

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

Primary Outcome Measures :
  1. Placebo-induced activation of brain opioid neurotransmission [ Time Frame: 90 min ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   20 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00200876

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United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
National Center for Complementary and Integrative Health (NCCIH)
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Principal Investigator: Jon-Kar Zubieta, MD, PhD University of Michigan
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Responsible Party: Jon-Kar Zubieta, Professor, University of Michigan Identifier: NCT00200876    
Other Study ID Numbers: R01AT001415-01A1 ( U.S. NIH Grant/Contract )
R01AT001415-01A1 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2005    Key Record Dates
Last Update Posted: March 24, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jon-Kar Zubieta, University of Michigan:
Positron-Emission Tomography
Pain Relief
Opioid Receptors