Inhibition of Non-histaminergic Pruritus Applied Using 3 Different Pruritogens

Study Overview
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Brief Summary
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With this experiment, we want to use to investigate whether repeated application of EMLA cream as a tool to modulate non-histaminergic itching, which is produced using small needles from the plant mucuna pruriens (it is known that antihistamine does not attenuate this form of itch) and we want to compare the effect of short (1 hour) and prolonged (3 hours) application of EMLA. The sub-project takes place in 3 sessions over a period of 3 consecutive days (24 hours apart). All sessions will be identical.

Official Title
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Evaluation of the Effect of Repeated Administration of Topical Local Anaesthetic Mixture of Lidocaine and Prilocaine (EMLA) in a Model of Non-histaminergic Itch Induced by Cowhage.

Conditions
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Itch

Intervention / Treatment
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* Drug: Emla 1 hour
* Drug: EMLA 3 hours
* Other: Vehicle cream for 1 hour
* Other: Vehicle cream for 3 hours
* Other: Cowhage


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 neurologic, musculoskeletal 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 antihistamine medications or pain killers. Skin diseases Hypersensitivity to papaya and mango fruit, cashew nuts and 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) Known history of anaphylactic shock, or local allergy (contact dermatitis) to lidocaine, prilocaine or other local anaesthetics of the amide type.

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: Emla 1 hour<br>* At the start of each session, the middle forearms of the subject will each be divided into two squared areas (4x4 cm). On each arm, the two areas will be located 4 cm apart. Then one area will be pre-treated with cutaneous 2.5% lidocaine/2.5% prilocaine cream (EMLA cream) for 1 hour.<br>Drug: EMLA 3 hours<br>* At the start of each session, the middle forearms of the subject will each be divided into two squared areas (4x4 cm). On each arm, the two areas will be located 4 cm apart. Then one area will be pre-treated with cutaneous 2.5% lidocaine/2.5% prilocaine cream (EMLA cream) for 3 hours.<br>Other: Vehicle cream for 1 hour<br>* At the start of each session, the middle forearms of the subject will each be divided into two squared areas (4x4 cm). On each arm, the two areas will be located 4 cm apart. Then two area will be pre-treated with a vehicle cream for 1 h.<br>Other: Vehicle cream for 3 hours<br>* At the start of each session, the middle forearms of the subject will each be divided into two squared areas (4x4 cm). On each arm, the two areas will be located 4 cm apart. Then two area will be pre-treated with a vehicle cream for 3 h.<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>|

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 9 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 9 minutes | 
| Superficial blood perfusion measurement | Superficial blood perfusion is measured by a Speckle contrast imager | After 1 hour | 
| Superficial blood perfusion measurement | Superficial blood perfusion is measured by a Speckle contrast imager | After 3 hours | 
| Superficial blood perfusion measurement | Superficial blood perfusion is measured by a Speckle contrast imager | 10 min after cowhage application | 
| Measuring Alloknesis | Alloknesis sensation is measured using a standardized sensory brush exerting a force of 200 to 400 mN. | After 1 hour | 
| Measuring Alloknesis | Alloknesis sensation is measured using a standardized sensory brush exerting a force of 200 to 400 mN. | After 3 hours | 
| Measuring Alloknesis | Alloknesis sensation is measured using a standardized sensory brush exerting a force of 200 to 400 mN. | 10 min after cowhage application | 
| Measuring Hyperknesis | Hyperknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force). | After 1 hour | 
| Measuring Hyperknesis | Hyperknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force). | After 3 hours | 
| Measuring Hyperknesis | Hyperknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force). | 10 min after cowhage application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measuring Erythema | The onset of erythema is measured with a spectrometer (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark). | After 1 hour | 
| Measuring Erythema | The onset of erythema is measured with a spectrometer (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark). | After 3 hours | 
| Measuring Erythema | The onset of erythema is measured with a spectrometer (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark). | 10 min after cowhage application | 
| Measuring Skin Pigmentation | The onset of skin pigmentation is measured with a spectrometer (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark). | After 1 hour | 
| Measuring Skin Pigmentation | The onset of skin pigmentation is measured with a spectrometer (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark). | After 3 hours | 
| Measuring Skin Pigmentation | The onset of skin pigmentation is measured with a spectrometer (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark). | 10 min after cowhage application |