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

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

Sponsors

Lead Sponsor: Aalborg University

Source Aalborg University
Brief Summary

In this experiment the investigators would like to assess if papain induces an itch sensation comparable to the itch sensation induced by cowhage and to confirm that the mechanism of action of papain follows the non-histaminergic pathway.

Detailed Description

The most used model of non-histaminergic itch is cowhage but this models presents several problems, such us the impossibility of standardizing the amount of the spicules inserted in the skin and the difficulty of obtaining the substance. These aspects bring us the necessity to find a new and more standardized model of non-histaminergic itch. Papain is a cysteine protease extracted from papaya plant that is known to cause itch if applied to the skin. The aim of this sub-project is to assess if papain induces an itch sensation comparable to the itch sensation induced by cowhage spicule and histamine. Moreover, this sub-project serves the purpose of evaluating if the anti-histamine treatment only reduces the histamine-induced itch without affecting cowhage and papain induced itch, underling the non-histaminergic mechanism of papain.

Overall Status Not yet recruiting
Start Date October 1, 2020
Completion Date June 2022
Primary Completion Date September 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Superficial blood perfusion 15 minutes
Measuring itch intensity by computerized Visual Analog Scale Scoring 15 minutes
Measuring pain intensity by computerized Visual Analog Scale Scoring 15 minutes
Measuring Alloknesis 15 minutes
Secondary Outcome
Measure Time Frame
Measurement of Cold Detection Thresholds (CDT) 15 minutes
Measurement of Cold PainThresholds (CPT) 15 minutes
Measurement of Heat Pain Thresholds (HPT) 15 minutes
Measurement of Warm Detection Thresholds (WDT) 15 minutes
Measurement of Pain to Supra-threshold Heat Stimuli 15 minutes
Measurement of Mechanical Pain Thresholds (MPT) 15 minutes
Measurement of Mechanical Pain Sensitivity (MPS) 15 minutes
Touch Pleasantness (TP) 15 minutes
Enrollment 20
Condition
Intervention

Intervention Type: Drug

Intervention Name: Doxepin Topical

Description: Four of the areas will be treated with doxepin for 1 hour and 30 minutes (with a patch to deposit 1.2 grams of cream). Each patch will be covered with Tegaderm I.V., an occlusive, adhesive dressing (3M), for at least 1½ hours

Arm Group Label: Doxepin Application

Intervention Type: Drug

Intervention Name: Papain

Description: Papain will be applied by 1 SPT prick thought the skin

Arm Group Label: Itch Induction

Intervention Type: Drug

Intervention Name: Histamine

Description: Histamine will be applied by 1 SPT prick thought the skin

Arm Group Label: Itch Induction

Intervention Type: Other

Intervention Name: Cowhage

Description: Cowhage spicules are 1-2 mm in length and have diameter of 1-3 µm at their tip. 30-35 spicules are gently rubbed into a 1 cm diameter skin area.

Arm Group Label: Itch Induction

Eligibility

Criteria:

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)

Gender: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Contact

Last Name: Silvia Lo Vecchio, PhD

Phone: 21397785

Email: [email protected]

Location
Facility: Contact: Aalborg University Silvia L Lo Vecchio, Phd 21397785 [email protected]
Location Countries

Denmark

Verification Date

October 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Aalborg University

Investigator Full Name: Silvia Lo Vecchio

Investigator Title: PhD, Assistant Professor

Has Expanded Access No
Number Of Arms 2
Arm Group

Label: Doxepin Application

Type: Experimental

Description: During the session each forearm of the subject will be divided into four squared areas (2.5x2.5 cm), see Figure 4. Four of the areas will be treated with doxepin for 1 hour and 30 minutes (with a patch to deposit 1.2 grams of cream). Each patch will be covered with Tegaderm I.V., an occlusive, adhesive dressing (3M), for at least 1½ hours 48. At the end of the pre-treatment period, the patches will be removed and the skin will be cleaned with alcohol.

Label: Itch Induction

Type: Experimental

Description: After Doxepin removal, Then tests with papain, cowhage, histamine or vehicle will be conducted. Each substance will be randomly applied in two areas, one pretreated with doxepin and one with no pre-treatment.

Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Basic Science

Masking: Single (Participant)

Source: ClinicalTrials.gov