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Effects of Anticipation of Pain Relief on Brain Mechanisms

This study has been completed.
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Jon-Kar Zubieta, University of Michigan Identifier:
First received: September 13, 2005
Last updated: March 21, 2017
Last verified: March 2017
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 Intervention
Pain Procedure: Hypertonic saline Procedure: Isotonic saline

Study Type: Interventional
Study Design: 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

Further study details as provided by Jon-Kar Zubieta, University of Michigan:

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

Enrollment: 60
Study Start Date: September 2003
Study Completion Date: June 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00200876

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)
Principal Investigator: Jon-Kar Zubieta, MD, PhD University of Michigan
  More Information

Responsible Party: Jon-Kar Zubieta, Professor, University of Michigan Identifier: NCT00200876     History of Changes
Other Study ID Numbers: R01AT001415-01A1 ( U.S. NIH Grant/Contract )
Study First Received: September 13, 2005
Last Updated: March 21, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
Analgesia processed this record on August 18, 2017