Conditions: Pain Measurement
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 10
Healthy volunteers: yes

Brief summary:
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

Detailed description:
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.

Arms:
arm 1: Experimental inflammation, and tissue injury sites were created, an infusion of alfentanil 100ng/ml was administered over 3 hours using a programmable infusion pump, and data were collected to measure inflammation, pain response, and cytokine levels locally. arm 2: Experimental inflammation and tissue injury sites were created, an infusion of propranolol 30ng/ml was administered over 3 hours using a programmable infusion pump, and data were collected to measure inflammation, pain response, and cytokine levels locally. arm 3: Experimental inflammation and tissue injury sites were created, an infusion of normal saline was administered over 3 hours using a programmable infusion pump, and data were collected to measure inflammation, pain response, and cytokine levels locally.

Interventions: intervention 1: Alfentanil intervention 2: Propranolol intervention 3: Placebo
Intervention descriptions: intervention 1: An infusion of alfentanil 100ng/ml was administered over 3 hours using a programmable infusion pump. intervention 2: An infusion of propranolol 30ng/ml was administered over 3 hours using a programmable infusion pump. intervention 3: An infusion of normal saline was administered over 3 hours using a programmable infusion pump to mimic the 2 drug arms,

Protocol document: