Repetitive Applications of Pruritogens and Effects of a Cutaneous-induced Pain Stimulation on Nonhistaminergic Itch Perception

Study Overview
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Brief Summary
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In This experiment, the investigators would like to test following hypotheses: the pain stimulation applied at the same time of a pruriceptive stimulus will decrease the itch perception. Moreover, also the effect of the cutaneous pain stimulus location (same forearm of the pruriceptive stimulus versus the opposite forearm) on histaminergic and non-histaminergic itch will be investigated.

Detailed Description
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The phenomenon that pain inhibits pain is a well-known mechanism, but it is not known if pain is inhibiting itch. In this context, the aim of this project is to investigate the extent to which thermal or neurogenic short cutaneous pain can affect the itch perception. In particular, the project aims to understand any differences in itch perception when the painful stimulation is applied on the same forearm versus the opposite forearm. The hypothesis is that by applying a painful stimulus at the same time of an itchy stimulus, the itch sensitivity will decrease; probably due to an inhibitory process conducted by interneurons (Bhlbb5 interneuron) at central level.

Official Title
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Repetitive Applications of Pruritogens and Effects of a Cutaneous-induced Pain Stimulation on Nonhistaminergic Itch Perception

Conditions
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Pain, Burning, Capsaicin

Intervention / Treatment
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* 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 addictive drugs Previous or current history of neurological (e.g. neuropathy), immunological (e.g. asthma, immune deficiencies, arthritis) musculoskeletal (e.g. muscular pain in the upper extremities,), cardiac disorder, or mental illnesses that may affect the results 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 (e.g. atopic dermatitis, pruritus nodularis, eczema, psoriasis) 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 one week of study entry (four 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: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: The sub-project takes place over three sessions on three consecutive days. The participants will randomly receive two pruritogens and two pain stimulations (heat or capsaicin) in the same and in the opposite arm.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pain<br>A thermode stimulator of 3x3 cm will be placed on the areas and kept in place by means of Velcro tape. The temperature raises 1°C per second from a starting temperature of 32°C until itch reach or 46.5 °C. This temperature will be maintained for 2 minutes. Then the temperature will return to baseline temperature at a rate of 5°C /s. | Other: Cowhage<br>* 25 spicules will be inserted in the center of the predefined skin area on the mandibular area. The spicules will be gently rubbed for 15-20 seconds in circular motion to facilitate epidermal penetration.<br>|
| Experimental: Capsaicin<br>Capsaicin patches (dosage form: transdermal patch 8% Qutenza, Astellas) will be applied on one squared area (4x4 cm2). The patch will be left in place for 20 minutes after which it will be removed. | Other: Cowhage<br>* 25 spicules will be inserted in the center of the predefined skin area on the mandibular area. The spicules will be gently rubbed for 15-20 seconds in circular motion to facilitate epidermal penetration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of itch intensity using a VAS scale | Immediately following the itch provocations, participants will be instructed to rate the itch intensity for 10 minutes using a digital visual analogue scale (VAS; eVAS Software: Aalborg, University, Denmark), on a tablet. The scale will be measured from 0 to 100, where 0 represents 'no itch' and 100 'worst itch imaginable'. | 1 minute post itch provocation | 
| Assessment of pain intensity using a VAS scale | Immediately following the itch provocations, participants will be instructed to rate the pain intensity for 10 minutes using a digital visual analogue scale (VAS; eVAS Software: Aalborg, University, Denmark), on a tablet. The scale will be measured from 0 to 100, where 0 represents 'no pain' and 100 'worst pain imaginable'. | 1 minute post itch provocation | 
| Retrospective rating of the pain perceived on a NRS | After 10 minutes of pruritogens application, a retrospective rating of the pain perceived from the thermal pain/capsaicin will be provided by the subject using a numeral rating scale (NRS) | 10 minutes post itch provocation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alloknesis | Alloknesis sensation is measured using a standardized sensory brush (SENSELab Brush-05, Somedic AB, Hörby, Sweden) exerting a force of 200 to 400 mN. | 12 minutes post itch provocation | 
| Mechanically evoked itch | Mechanically evoked itch is measured using three von Frey filaments of 4.08, 4.16 and 4.31 (1.0, 1.4, 2.0 g, respectively) (North Coast Medical, Gilroy, CA). The center of the skin area is stimulated by 3 pricks, repeated 3 times in short succession. After a total of 9 stimulations, the participants will report the itch elicited on a numerical rating scale (NRS) from 0 to 10 (0 = no itch; 10 = worst imaginable itch). | 15 minutes post itch provocation |