Characterization of Bovine Adrenal Medulla as a New Surrogate Model of Non-histaminergic Itch

Study Overview
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Brief Summary
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With this experiment, the experimenter wish evaluate the role of TRPA1 on non-histaminergic itch induced by BAM8-22

Detailed Description
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With this experiment, the experimenter wish evaluate the role of TRPA1 on non-histaminergic itch induced by BAM8-22 2 (Bovine Adrenal Medulla), which is found naturally in the human body and which has proved to evoke itch. To evaluate the role of TRPA1 it will be used a TRPA1 antagonist (A-967079)

Official Title
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Characterization of Bovine Adrenal Medulla (BAM8-22) as a New Surrogate Model of Non-histaminergic Itch

Conditions
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Itch

Intervention / Treatment
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* Drug: A-967079 and BAM8-22 application
* Drug: A-967079 and BAM8-22 application after 5 minutes.
* Drug: A-967079 application.
* Drug: Vehicle and BAM8-22 application.


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 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.) Moles, wounds, scars or tattoos in the area to be treated or tested Lack of ability to cooperate • Current use of medications that may affect the trial such as antihistamines and pain killers. Skin diseases 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
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A-967079 Injections + BAM8-22<br> | Drug: A-967079 and BAM8-22 application<br>* A-967079 solution (in PBS 0.5 mg/ml, subcutaneous injection of 0.1ml) and BAM8-22 with inactivate cowhage spicules 20 µl of BAM8-22 will be applied to a previously determined area on the volar forearm using inactivate cowhage spicules<br>Drug: A-967079 and BAM8-22 application after 5 minutes.<br>* A-967079 solution (in PBS 0.5 mg/ml, subcutaneous injection of 0.1ml). BAM8-22 with inactivate cowhage spicules 20 µl of BAM8-22 will be applied 5 minutes after to a previously determined area on the volar forearm using inactivate cowhage spicules<br>|
| Experimental: A-967079 Injections and vehicle<br> | Drug: A-967079 application.<br>* A-967079 solution (in PBS 0.5 mg/ml, subcutaneous injection of 0.1ml) will be applied to a previously determined area on the volar forearm<br>Drug: Vehicle and BAM8-22 application.<br>* Vehicle (in PBS, subcutaneous injection of 0.1ml) and BAM8-22 with inactivate cowhage spicules 20 µl of BAM8-22 will be applied to a previously determined area on the volar forearm using inactivate cowhage spicules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| superficial blood perfusion | is measured by a speckle contrast imager (FLPI, Moor Instruments, England) | change from baseline, up to 10 minutes after the application | 
| Warm Detection Threshold, and Heat Pain threshold | he tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device | change from baseline, up to 10 minutes after the application | 
| Cold Detection Threshold and Cold Pain threshold | the tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device | change from baseline, up to 10 minutes after the application | 
| Pain supra-threshold heat Stimuli | the tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device | change from baseline, up to 10 minutes after the application | 
| Alloknesis | s measured by using a mildy pruritic, non-painful von Frey filaments of a predetermined intensity (generally 5-30 milliNewton of force) | change from baseline, up to 10 minutes after the application | 
| mechanical pain threshold and sensitivity | is performed using a pin-prick set (Aalborg University). The set consists of 8 needles each having a diameter of 0,6 mm and different force applications | change from baseline, up to 10 minutes after the application | 
| itch rating | the subject will rate the itch for 10 minutes by using a visual analog scale (VAS) on a tablet. this scale goes from 0 to 100. 0 indicates no itch and 100 indicates worst imaginable itch | change from baseline, up to 10 minutes after the application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain rating | the subject will rate the pain for 10 minutes by using a visual analog scale (VAS) on a tablet. this scale goes from 0 to 100. 0 indicates no pain and 100 indicates worst imaginable pain | change from baseline, up to 10 minutes after the application |