Clinical trial NCT00200876: Effects of Anticipation of Pain Relief on Brain Mechanisms
Official title: Neurochemical Mediation of Placebo Responses in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain
Keywords: Positron-Emission Tomography
Endorphins
Pain Relief
Opioid Receptors
Stress
Analgesia
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2005-09-20
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Placebo-induced activation of brain opioid neurotransmission
timeFrame: 90 min
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
Study officials:
affiliation: University of Michigan
name: Jon-Kar Zubieta, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: