Study on the Effect of a Beta Blocker on Increased Sensitivity to Pain in Humans Caused by Opioids

Recent evidence suggests that opioid therapy may cause a biphasic response, i.e. initial pain
relief followed paradoxically by a longer lasting hypersensitivity to pain. Recent genetic
analysis in mice suggests that beta adrenergic receptor antagonists reduce opiate-induced
hyperalgesia (OIH). The purpose of this study is to determine the analgesic and
antihyperalgesic properties of the beta-blocker propranolol on remifentanil-induced
hypersensitivity in humans.

The investigators want to determine the analgesic and antihyperalgesic properties of the
beta-blocker propranolol on remifentanil-induced hypersensitivity in humans. The
investigators hope to learn whether the administration of beta-blocker propranolol will
significantly diminish the hyperalgesic response after administration of an opioid.

The primary outcome measure for this study is change in size (area) of secondary hyperalgesia
after cessation of remifentanil infusion, a measure of OIH.

Inclusion Criteria:

1. Healthy men,

2. Age between 18 and 45 years

3. Normal weight (according to the table provided by Metropolitan Life Insurance).

Exclusion Criteria:

1. Hypersensitivity to opioids or naloxone,

2. History of addictive disease,

3. Significant cardiac, respiratory, gastrointestinal, neurological, dermatological, and
psychiatric diseases,

4. Concurrent medication with an analgesic drug,

5. Student and employees affiliated with our laboratory