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.

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.

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