The Effect of High-dose 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 High-dose 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: Men or women, aged between 19 and 40 years 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 Regular consumption of very spicy (capsaicin containing) food Allergy against any medication used in the study protocol

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: 1<br>Remifentanil | Drug: Remifentanil<br>* Remifentanil (Ultiva®; Glaxo-Smith-Kline; Vienna, Austria) will be applied intravenously during 60 minutes through a dedicated infusion pump (TCI Alaris PK Syringe Pump, Cardinal Health, Baesweiler, Germany), with a Target Controlled Infusion (following the integrated software algorithm by Minto), reaching the initial 18ng/ml plasma concentration in 180 seconds. This corresponds to circa 0.7 µg kg-1 min-1<br>|
| Active Comparator: 2<br>Midazolam | Drug: Midazolam<br>* Midazolam (Dormicum®; Roche; Vienna, Austria) will be applied intravenously as active placebo at a dose of 15 µg kg-1 min-1 over 5 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 |
| --- | --- | --- |
| Pain immediately after injection |  | 0-15 min | 
| Stimulus-response (SR) function to a set of modified rigid von Frey filaments (8-512 mN) |  | 0-6 hours | 
| 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 |  | 30 and 59 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