The Effect of Remifentanil on Established Capsaicin-Induced Hyperalgesia in Human Volunteers

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. Intradermal injection of capsaicin (injection of pepper extract into the skin) is an established pain model in humans. The investigators want to test the influence of remifentanil, an ultra-short acting opioid, on hyperalgesia observed after intradermal capsaicin in human volunteers in a double blind cross-over prospective active placebo controlled clinical trial.

Official Title
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The Effect of Remifentanil on Established Capsaicin-Induced Hyperalgesia in Human Volunteers

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

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remifentanil<br> | Drug: Remifentanil<br>* Remifentanil (Ultiva ®; Glaxo-Smith-Kline; Vienna, Austria) at an initial dose of 0.24 µg kg-1 min-1 will be applied iv during 60 minutes.<br>|
| Placebo Comparator: Midazolam<br>Active Placebo | Drug: Midazolam<br>* Midazolam (Dormicum®; Roche; Vienna, Austria) will be applied iv as active placebo at a dose of 7.5 µg.kg-1.min-1 over 10 minutes to mimic typical central nervous side effects of remifentanil.<br>|

What is the study measuring?
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Primary Outcome Measures

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

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) |  | 0-6 hours | 
| Pain immediately after injection |  | 0-15 minutes | 
| Heat pain threshold within the area of mechanical hyperalgesia |  | 0-6 hours | 
| Mechanical pain threshold within the area of pin prick hyperalgesia, area of dynamic allodynia to brush |  | 0-6 hours | 
| Adverse effects |  | 10 and 30 min after infusion of study medication | 

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