Effect of Nalbuphine and Naloxone on Experimentally Induced Skin Sensitivity

Study Overview
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Brief Summary
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In previous clinical studies of post-surgical pain the investigators found that nalbuphine (Nubain), a narcotic pain killer, relieves pain more effectively when combined with low-dose naloxone (Narcan), a drug that is used to treat narcotic overdose. This finding was particularly true in men. The purpose of this study is to find out if nalbuphine combined with naloxone is more effective in relieving experimentally produced pain than either drug alone. A second reason for this study is to find out if study medications work more effectively in women or in men. Subjects will come to the University of California at San Francisco (UCSF) Clinical Research Center (CRC) for 4 study visits. The first visit will be a 2-hour screening to assess the subject for study eligibility. During the other three visits, the investigators will use a thermal stimulating device to produce temporary, non-injurious skin sensitivity that subjects will feel as painful. Changes in pain will be measured following the intravenous (i.v.) administration of study drugs. Three drug combinations will be administered, a different one each visit: 1) nalbuphine 5 mg and naloxone 0.4 mg , 2) naloxone 0.4 mg and saline (an inactive solution), nalbuphine 5 mg and saline. These drug combinations will be administered in random order; all subjects will receive all three combinations.

Official Title
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Effect of Kappa Opioid Agonist-Antagonists in the Heat/Capsaicin Sensitization Model

Conditions
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Healthy

Intervention / Treatment
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* Drug: nalbuphine plus naloxone
* Drug: nalbuphine plus saline
* Drug: naloxone plus saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 40 In stable health Speak, read, understand English language If female, must be non-lactating and not pregnant Exclusion Criteria: Heat pain detection thresholds above 47 ºC/116.6 ºF Inability to develop secondary hyperalgesia from the heat and capsaicin stimulation performed at the screening visit Serious psychiatric psychopathology (psychotic disorder, substance abuse) Tattoos in the area of measurements Allergy to study drugs (nalbuphine, naloxone, or capsaicin) Current or recent use opioids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Women<br>Both arms of this study will receive identical interventions. The only difference will be the sex of the participants in each study arm. | Drug: nalbuphine plus naloxone<br>* single dose administered intravenously<br>* Other names: Narcan;Drug: nalbuphine plus saline<br>* single dose administered intravenously<br>* Other names: Nubain;Drug: naloxone plus saline<br>* single dose administered intravenously<br>* Other names: Narcan;|
| Experimental: Men<br>Both arms of this study will receive identical interventions. The only difference will be the sex of the participants in each study arm | Drug: nalbuphine plus naloxone<br>* single dose administered intravenously<br>* Other names: Narcan;Drug: nalbuphine plus saline<br>* single dose administered intravenously<br>* Other names: Nubain;Drug: naloxone plus saline<br>* single dose administered intravenously<br>* Other names: Narcan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Skin Sensitivity as Measured by a Visual Analog Scale | Participants would have been asked to rate the level of pain on a scale from 0 (no pain) to 10 (worst pain imaginable). | Prior to drug administration and 20 minutes, 70 minutes and 2 hours after each drug administration |