Evaluation of Propranolol's Effect on Pain and Inflammation.

Previous studies have shown that the beta-adrenergic system plays a role in processing pain and the expression of hyperalgesia. Recent studies have investigated the analgesic effects, and potential anti-hyperalgesic effects (using a model of opioid induced (OIH) hyperalgesia) of propranolol, a beta adrenergic antagonist. We plan to further investigate the analgesic effects, and the potential anti inflammatory effects, of propranolol and compare those effects to alfentanil, an opioid of known effect, and placebo

This study is a double blind-placebo controlled study in which subjects will be exposed to propranolol infusion during one study day, the opioid alfentanil on another day, and placebo infusion during a third study day. The infusion order will be randomized, and the participant and individual conducting the pain testing will both be blinded to the treatment.

Propranolol, alfentanil, and placebo infusions will be administered intravenously using a computer-controlled infusion pump that can be set to accurately administer a target plasma concentration of drug.

On one study day subjects will receive propranolol at a target concentration of 30ng/ml over 3 hours time. On another study day subjects will receive 100ng/ml alfentanil over 3 hours, and on a third study day subjects will receive placebo (normal saline) using a computer-controlled infusion paradigm.

Sites to be evaluated for response to propranolol and placebo will be established in 2 ways. One will use ultraviolet B (UVB) exposure to create a "sunburn" causing inflammation and pain. The other will be a model of acute injury using an array of micro-needles.

Means of evaluation of injured, and non-injured sites will be pain testing (heat and mechanical pain thresholds will be established), interstitial fluid sampling for detection of pro-inflammatory, and pro-nociceptive cytokines, and laser doppler evaluation of tissue perfusion.

Subjects will be recruited using flyers. Interested participants will contact the study team, their questions will be answered, and an appointment for screening will be made.

Eligibility Criteria:
Inclusion Criteria:1) Age 18-65 2) Skin type II-IV according to classification of Fitzpatrick 3) Willing and able to sign an informed consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization and to comply with study procedures

Exclusion Criteria:1) History of acute or chronic illness that contraindicate the use of propranolol, may hinder study procedures, or confuse interpretation of the data (e.g. cardiac, dermatological, neurological, psychiatric or addictive diseases) 2) Clinically significant cardiovascular, pulmonary, hepatic or renal diseases 3) Pregnant or breast-feeding 4) Intake of prescription drugs with anti/pro-inflammatory action 5) Intake of prescription drugs with anti/pro-analgesic action 6) Inability to abstain from any anti/pro-inflammatory, or analgesic drugs 48 hours before, or during the study session 7) Inability to obtain at least 6 hours of sleep during the night preceding the study session 8) Known sensitivity or allergy to propranolol or alfentanil 9) Any history of drug or alcohol abuse