Study on the Development of Opioid Induced Hyperalgesia (OIH) After Exposure to Alfentanil

Study Overview
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Brief Summary
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The purpose of this study was to follow a person's response to experimental pain after multiple consecutive exposures to alfentanil or diphenhydramine to see if the person can tolerate the pain more, less, or the same at the end of the study.

Detailed Description
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This project investigates the phenomenon of opioid-induced hyperalgesia (OIH). Opioid analgesics, in addition to their therapeutic anti-nociceptive effects, under some conditions produce pro-nociceptive effects. This phenomenon of pain or pain sensitivity being increased by prior opioid administration is called opioid-induced hyperalgesia. It is thought to be relevant both to pain management complications and to complications of opioid dependence and its treatment. This study investigated the time-course of opioid-induced hyperalgesia development in healthy normal volunteers (N=12 completers), using a series of acute alfentanil administrations (15 mg/kg mg intramuscular (IM) per day) spaced at 3-4 day intervals, with testing for pain tolerance using the cold pressor test (CPT), and mechanical quantitative sensory testing (MQST) each administered repeatedly over time within each testing day. The goal was to determine the time course of OIH development following acute opioid administration, and to assess whether this changes over repeated acute opioid administrations.

Official Title
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A Pilot Study of Prolonged, Intermittent Exposure to Alfentanil on Opioid-Induced Hyperalgesia in Healthy Volunteers

Conditions
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Hyperalgesia

Intervention / Treatment
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* Drug: Alfentanil
* Drug: Diphenhydramine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-55 No active medical conditions BMI between 20-30 Able and willing to perform/tolerate pain procedures Able to communicate in English Exclusion Criteria: Lifetime substance use disorder, except for alcohol abuse/dependence in remission Use of opiates in last 3 months Ongoing marijuana use Acute or chronic pain Neurologic or psychiatric condition known to influence cold pressor testing (peripheral neuropathy, major depression, or schizophrenia) Current use of prescribed or over the counter pain medications Previous adverse reaction to opiate medications or diphenhydramine Use of tobacco or caffeine on study days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alfentanil<br>Subjects received a series of acute alfentanil administrations each session (15 mcg/kg IM per session), with sessions spaced at 3-4 day intervals. | Drug: Alfentanil<br>* 15 mcg/kg IM<br>|
| Active Comparator: Diphenhydramine<br>Subjects received a series of acute diphenhydramine administrations each session (25 mg IM per session), with sessions spaced at 3-4 day intervals. | Drug: Diphenhydramine<br>* 25 mg IM<br>* Other names: Benadryl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Tolerance | The participant places their hand in a water bath kept at 4 degrees Celsius (cold pressor test). They then continue to hold the hand in the water bath until they can no longer tolerate the pain (pain tolerance) or until the end of the testing (truncated at 300 seconds for safety purposes). Reported as the mean (time to hand removal in seconds) at the 30 minute time point. | 8 sessions over 4-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Threshold | The amount of time (in seconds) before the participant first verbally reports feeling pain after placing hand in 4 degree Celsius circulating water bath at the 30 minute time point. Truncated at 300 seconds for safety purposes. | 8 sessions over 4-6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid induced hyperalgesia