The Effect of High-dose Remifentanil on Established Sunburn-induced Hyperalgesia in Human Volunteers (HighDose RemiSun)

Study Overview
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Brief Summary
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Treatment of chronic pain is a major clinical challenge since chronic pain is frequent and leads to deterioration of quality of life. An injury or wound can lead to long term changes in the nervous system that make the skin more sensitive at and near the injury; this is termed hyperalgesia and occurs through long term depotentiation (LTP), i.e., a change in the synaptic interaction between neurons. Opioids are the gold standard for the symptomatic therapy of moderate to severe pain. Now, in animal studies the investigators have discovered previously unrecognized effects of opioids. UV-B irradaition of the skin of the thigh is an established model of priamary and secondary hyperalgeisa in humans. The investigators want to test the influence of remifentanil, an ultra-short acting opioid, on hyperalgesia observed after UV-B irradiation in human volunteers in a double blind cross-over prospective active placebo controlled clinical trial, at a dose corresponding to 0.7 µg kg-1 min-1.

Official Title
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The Effect of High-dose Remifentanil on Established Sunburn-induced Hyperalgesia in Human Volunteers (HighDose RemiSun)

Conditions
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Hyperalgesia

Intervention / Treatment
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* Drug: Remifentanil
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index between 15th and 85th percentile Normal findings in the medical history and physical examination Drug free for 1 week prior to the study day Exclusion Criteria: Regular use of medication especially analgesics Abuse of alcoholic beverages, drug abuse History of asthma Participation in a clinical trial in the 2 weeks preceding the study Symptoms of a clinically relevant illness in the 2 weeks before the first study day Resting systolic blood pressure > 135 mmHg or diastolic blood pressure > 85 mmHg Acute skin diseases like sunburn on the relevant areas or skin lesions Pregnancy or breast feeding UV sensitive skin conditions, like Xeroderma pigmentosa

Ages Eligible for Study
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Minimum Age: 19 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: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remifentanil<br>Remifentanil Infusion | Drug: Remifentanil<br>* Remifentanil Infusion<br>* Other names: Ultiva;|
| Active Comparator: Midazolam<br>Active Placebo | Drug: Midazolam<br>* Midazolam Infusion<br>* Other names: Dormicum;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure: Area of pin prick hyperalgesia |  | 0-6h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stimulus-response (SR) function to a set of modified rigid von Frey filaments (8-512 mN) |  | 0-6h | 
| Heat pain threshold within the area of mechanical hyperalgesia |  | 0-6h | 
| Mechanical pain threshold within the area of pin prick hyperalgesia, area of dynamic allodynia to brush |  | 0-6h | 
| Adverse effects |  | 30 and 59 min after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sunburn, Remifentanil, Hyperalgesia