Investigation of a New Human Model for Itch

Study Overview
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Brief Summary
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This third sub-project aims to evaluate the interaction between the TRPM8 receptor and pruritus by studying the anti-pruritic effect of TPRM8-agonist L-menthol on histaminergic and non-histaminergic itch induced using three different pruritogens: histamine, cowhage and papain.

Official Title
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Characterization of New Human Models of Non-histaminergic Itch and Their Interaction With the TRPM8 Receptor

Conditions
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Itch

Intervention / Treatment
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* Other: Papain
* Other: Histamine
* Other: Cowhage
* Other: L-menthol


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: Pregnancy or lactation Drug addiction defined as any use of cannabis, opioids or other addictive drugs Previous or current history of neurological, dermatological, immunological musculoskeletal, cardiac disorder or mental illnesses that may affect the results (e.g. neuropathy, muscular pain in the upper extremities, etc.). 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. Skin diseases Moles, scars or tattoos in the area to be treated or tested. Hypersensitivity to papaya and mango fruit, cashew nuts, rubber latex 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> | Other: Papain<br>* Papain will be applied using cowhage spicules inactivated by heat<br>Other: Histamine<br>* To deliver histamine, standard allergy skin prick test (SPT) lancets are applied<br>Other: Cowhage<br>* Cowhage spicules are 1-2 mm in length and have a diameter of 1-3 μm. The spicules are inserted by gently rubbing 30-35 spicules into a 1 cm diameter skin area.<br>Other: L-menthol<br>* A 1 mL aliquot is dispensed onto a 2,5 × 2,5 cm cotton pad and placed on a 6 × 6 cm sheet of medical tape.<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 15 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 15 minutes | 
| Superficial blood perfusion measurement | Superficial blood perfusion is measured by a Speckle contrast imager | After 15 minutes | 
| Measuring Alloknesis | Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 milliNewton of force). | 15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Cold Detection Thresholds (CDT) | The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. | 15 minutes | 
| Measurement of Cold PainThresholds (CPT) | The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. | 15 minutes | 
| Measurement of Heat Pain Thresholds (HPT) | The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. | 15 minutes | 
| Measurement of Warm Detection Thresholds (WDT) | The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. | 15 minutes | 
| Measurement of Pain to Supra-threshold Heat Stimuli | The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. | 15 minutes | 
| Measurement of Mechanical Pain Thresholds (MPT) | This test is conducted using a pin-prick set. | 15 minutes | 
| Measurement of Mechanical Pain Sensitivity (MPS) | This test is conducted using a pin-prick set. | 15 minutes | 
| Touch Pleasantness (TP) | Pleasant touch sensation measured using a standardized sensory brush | 15 minutes |