Evaluation of Peripheral Itch Mechanisms Following Injection of Morphine (Second Sub-Project)

Study Overview
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Brief Summary
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The aim of our 2nd sub-project is to clarify if the capsaicin receptor TRPV1 is implicated in the mechanism of morphine-induced mast cell degranulation. Moreover, we also aim to clarify if the mechanism of opioid-induced itch relay on the histaminergic pathway by using the antihistamine (diphenhydramine) to suppress the release of histamine from peripheral mast cells.

Official Title
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Effect of Intradermal Morphine Application on Histaminergic and Non-histaminergic Itch and Related TRPV1 and Antihistamine Treatments (2nd Sub-project)

Conditions
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Itch

Intervention / Treatment
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* Drug: Capsaicin
* Drug: Diphenhydramine
* Drug: Morphine Chloride
* Drug: Isotonic saline
* Drug: Histamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women 18-60 years Speak and understand English Exclusion Criteria: Participants with any clinically significant abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results. Pregnancy or lactation Drug addiction defined as any use of cannabis, opioids or other addictive drugs Lack of ability to cooperate Current use of medications that may affect the trial such as antihistamines, antipsychotics and pain killers as well as systemic or topical steroids. Participants with known allergy/discomfort to the opioid morphine and antihistamine. Skin diseases Moles, scars or tattoos in the area to be treated or tested. Consumption of alcohol or painkillers 24 hours before the study days and between these Acute or chronic pain Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical trials)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br> | Drug: Capsaicin<br>* A capsaicin patch will be applied on a 3x3 cm squared area on the volar forearm. The patch will be left in place for 24h after which it will be removed.<br>Drug: Diphenhydramine<br>* Diphenhydramin cream 1% (Restamine®) will be applied on a 3x3 cm squared predetermined area on the volar forearm for 24 hours.<br>* Other names: Antihistamine;Drug: Morphine Chloride<br>* Morphine solution (0.1mg/ml, Morphine Hydrochloride) 50 μl will be applied intradermally to the center of a predetermined area on the volar forearm by a 1 ml syringe.<br>Drug: Isotonic saline<br>* injections of isotonic saline (0.05 ml, 0.9%) as vehicle will be performed.<br>Drug: Histamine<br>* A small drop of histamine dihydrochloride (1%, in saline) will be applied to a previously determined area on the volar forearm followed by a prick through the drop.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measuring itch intensity by computerized Visual Analog Scale Scoring | We will ask the subjects to rate the sensation of itch on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates no itch and 100 indicates worst itch imaginable. | For 10 minutes | 
| Measuring pain intensity by computerized Visual Analog Scale Scoring | We will ask the subjects to rate the sensation of pain on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates no pain and 100 indicates worst pain imaginable. | For 10 minutes | 
| Superficial blood perfusion measurement | Superficial blood perfusion is measured by a Speckle contrast imager | After 15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| While size | While size will be assessed using a ruler | After 15 minutes |