TRPV Expression in Subjects With Sensitive Skin

Study Overview
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Brief Summary
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Sensitive skin syndrome is defined as the presence of burning, itching or any other unpleasant sensation on the skin, due to physical, chemical or psychological factors. It is frequently a self-diagnosed condition, and there are no accurate tests to recognize or quantify it because of the individual variations in perception and intensity of the related symptoms. The most accepted physiopathogenic theory is the presence of an altered barrier function of epidermis. Also, changes in the pH of the stratum corneum have been found to induce skin sensitivity through the activation of the transient potential receptor vanilloid (TRPV) neuronal receptors. TRPV1 has been found in human keratinocytes, although its physiologic role in the skin is not yet established. Their presence in keratinocytes and cutaneous nervous fibers suggests a role in the sensitive function of the epidermis. Since this receptors can be activated by low pH (< 5.9), which is also important for the development of sensitive skin, we hypothesized that an increase in the expression of these receptors can be the responsible for the syndrome.

Detailed Description
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Sensitive skin syndrome is defined as the presence of burning, itching or any other unpleasant sensation on the skin, due to physical, chemical or psychological factors. It is frequently a self-diagnosed condition, and there are no accurate tests to recognize or quantify it because of the individual variations in perception and intensity of the related symptoms. Although the pathogenesis of sensitive skin syndrome is not completely understood, the most accepted theory is the presence of an altered barrier function. Irritation results from the abnormal penetration of substances to deeper layers of the skin, where they can induce vasodilation and stimulate c-type neuronal fibers. Also, changes in the pH of the stratum corneum have been found to induce skin sensitivity through the activation of the transient potential receptor vanilloid (TRPV) neuronal receptors. TRPV1 was first discovered in 1997, when it was identified as the specific receptor for capsaicin in a subgroup of nociceptors. It is a non-selective thermo-sensitive cationic channel that can be found in nerves from the central and peripheral nervous system, fibroblasts, smooth muscle, mast cells, endothelial cells, gastrointestinal, respiratory and urinary epithelial cells. TRPV1 can be activated by excessive heat (>42ºC), acidic pH (< 5.9), and also by endogenous substances such as N- arachidonoyl dopamine, leucotriene B, phospholipase C, and many others. In 2001, the functional expression of TRPV1 was identified in human keratinocytes. Their physiologic role in the skin has not been completely understood, but they have been related to differentiation, proliferation, inflammation and homeostasis of the epidermal barrier. Their presence in keratinocytes and cutaneous nervous fibers suggests a role in the sensitive function of the epidermis. It has been proved that the stimulation of TRPV1 in neuronal cells can induce pruritus and burning sensation. In vitro studies have demonstrated that the exogenous stimulation of TRPV1 in keratinocytes induces the release of nitric oxide, ATP, dopamine, prostaglandins, and other pro-inflammatory substances that can act as paracrine mediators between keratinocytes and cutaneous nerve fibers. Therefore, there are scientific bases to hypothesize that an increase in the expression of these receptors can be the responsible for the sensitive skin syndrome.

Official Title
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Distribution and Expression of Non-neuronal Transient Receptor Potential (TRPV) Ion Channels in Sensitive Skin Syndrome.

Conditions
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Sensitive Skin

Intervention / Treatment
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* Procedure: Skin biopsy
* Procedure: Oral mucosa specimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old Known response to the lactic acid stinging test Informed signed consent Exclusion Criteria: Any dermatoses in the test area Use of topical medications in the test area Personal history of keloid or hypertrophic scarring Known allergy to lidocaine Know heart disease Pregnancy Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sensitive Skin<br>Subjects with sensitive skin, diagnosed by the lactic acid stinging test. Skin biopsy Oral mucosa specimen | Procedure: Skin biopsy<br>* Two skin biopsies will be taken with a 3 mm punch in the retroauricular area. The procedure will be done by an investigator, under aseptic and antiseptic conditions and under local anesthesia with lidocaine and epinephrine. The incision will be sutured with 6-0 Nylon, and the stitches will be removed after 5 days. One biopsy will be processed for immunohistochemistry, the other for RNA extraction and analysis.<br>* Other names: Skin biopsy by punch;Procedure: Oral mucosa specimen<br>* The sample for keratinocytes from oral mucosa will be taken with a Foam knife, which is a non-invasive procedure. It does not need anesthesia, and it does not leave scars. The procedure consists in gently brush the oral mucosa with the knife five times, and the material that will be obtained will be fixed in a PBS solution for RNA analysis.<br>* Other names: Oral mucosa swap;|
| Active Comparator: Non-sensitive skin<br>Subjects without sensitive skin, determined by a negative lactic acid stinging test Skin biopsy Oral mucosa specimen | Procedure: Skin biopsy<br>* Two skin biopsies will be taken with a 3 mm punch in the retroauricular area. The procedure will be done by an investigator, under aseptic and antiseptic conditions and under local anesthesia with lidocaine and epinephrine. The incision will be sutured with 6-0 Nylon, and the stitches will be removed after 5 days. One biopsy will be processed for immunohistochemistry, the other for RNA extraction and analysis.<br>* Other names: Skin biopsy by punch;Procedure: Oral mucosa specimen<br>* The sample for keratinocytes from oral mucosa will be taken with a Foam knife, which is a non-invasive procedure. It does not need anesthesia, and it does not leave scars. The procedure consists in gently brush the oral mucosa with the knife five times, and the material that will be obtained will be fixed in a PBS solution for RNA analysis.<br>* Other names: Oral mucosa swap;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of TRPV1 | Determine the expression of TRPV1 in patients with sensitive skin | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TRPV1 and Sensitive Skin | Correlate the expression of TRVP1 with the presence of sensitive skin syndrome | Up to 1 year | 
| TRPV1 and skin phototype | Identify variations in the expression of TRPV1 according to skin phototype | Up to 1 year | 
| TRPV1 and barrier function | Correlate the expression of TRPV1 with the transepidermal water loss as an indirect measure of barrier function. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skin Phototype, Sensitive skin, Transient potential receptor vanilloid 1, TRPV1, Transepidermal water loss, Lactic acid test, Skin irritancy tests