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

Stanford University

Status and phase: Completed; Phase 2

Conditions: Hyperalgesia

Treatments: Drug: Remifentanil; Drug: Propranolol; Drug: Placebo to Match Propranolol

Study type: Interventional

Funder types: Other

Identifiers

NCT01222091

SU-10062010-7050

Details and patient eligibility

About

This research study explores whether a beta-blocker (propranolol) can prevent a person from becoming more sensitive to pain after administration of an opioid (remifentanil). Beta blockers inhibit the sympathetic (fight or flight) response and are often used to treat angina and high blood pressure. In a previous study in human volunteers, the investigators demonstrated an increased sensitivity to pain after a 60-minute infusion of the opioid remifentanil. The goal of this study is to identify a possible inhibitor of this phenomenon.

Full description

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.

Enrollment: 10 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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10 participants in 2 patient groups, including a placebo group

Propranolol, Then Placebo

Active Comparator group

Description:

Propranolol, a beta blocker, or placebo to match, will be given to test whether or not it could modulate the expression of remifentanil-induced postinfusion hyperalgesia (RPH) during two pain test including: mechanically evoked pain to map the size of the hyperalgesic skin region caused by electrical stimulation and heat pain.

Treatment:

Drug: Placebo to Match Propranolol

Drug: Propranolol

Drug: Remifentanil

Placebo, Then Propranolol

Placebo Comparator group

Description:

Propranolol, a beta blocker, or placebo to match, will be given to test whether or not it could modulate the expression of remifentanil-induced postinfusion hyperalgesia (RPH) during two pain test including: mechanically evoked pain to map the size of the hyperalgesic skin region caused by electrical stimulation and heat pain.

Treatment:

Drug: Placebo to Match Propranolol

Drug: Propranolol

Drug: Remifentanil