Effect of High Dose Naloxone on Secondary Hyperalgesia

Study Overview
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Brief Summary
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Recent studies have focused on the role of endogenous opioids on central sensitization. Central sensitization is known to be impaired or altered in chronic pain conditions, as fibromyalgia or chronic tension headache. Animal studies have shown reinstatement of mechanical hypersensitivity following naloxone administration after resolution of an injury. This suggests latent sensitization. In the present study, investigators hypothesize that naloxone (2 mg/kg) can reinstate secondary hyperalgesia 168 hours after a first-degree burn-injury. Investigators aim therefore to show that latent sensitization is present in humans and is modulated by endogenous opioids.

Official Title
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Effect of a High-dose Naloxone Infusion on Secondary Hyperalgesia After a First-degree Burn

Conditions
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Hyperalgesia, Pain, Naloxone, Opioid Antagonist

Intervention / Treatment
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* Drug: Naloxone (2 mg/kg)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy man written informed consent ASA 1-2 BMI 18 < BMI < 30 normal ultrasound examination of the heart normal ECG urin sample without traces of opioids Exclusion Criteria: volunteers, who do not understand the Danish language participation in another experimental trial in the previous 60 days nerve damage or skin lesions in the assessment areas neurological or psychiatric condition use of psycho-active drugs abuse of alcohol or drugs chronic pain regular use of pain-killers (> 1 a week) allergy against morphine or other opioids (including naloxone) use of prescription drugs 1 week prior to the trial use of over-the-counter medication 48 hours prior to the trial urin sample with traces of opioids volunteer is not suitable for the trial according to the investigator's consideration

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 35 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The effect of naloxone (2 mg/kg) on secondary hyperalgesia 168 hours after a first-degree burn-injury is compared to the placebo effect. | Drug: Placebo<br> <br> |
| Experimental: Naloxone (2 mg/kg)<br>The effect of naloxone (2 mg/kg) on secondary hyperalgesia 168 hours after a first-degree burn-injury is compared to the placebo effect. | Drug: Naloxone (2 mg/kg)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Secondary hyperalgesia area (cm2) surrounding a first-degree burn injury before and after infusion of naloxone/placebo | Areas of secondary hyperalgesia surrounding a first degree burn-injury will be assessed before and after infusion of naloxone/placebo. | 1h, 2h, 3h, 168h, 168h15min, 168h30min post-burn | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in allodynic area (cm2) surrounding a first-degree burn injury before and after infusion of naloxone/placebo | Areas of allodynia surrounding a first degree burn-injury will be assessed before and after infusion of naloxone/placebo. | 1h, 2h, 3h, 168h, 168h15min, 168h30min post-burn | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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secondary hyperalgesia, allodynia, mechanical pain threshold, naloxone, endogenous opioids, pain