Desensitization of Nociceptive Afferents by Application of Topical Capsaicin, Trans-cinnamaldehyde and L-menthol

April 25, 2017 updated by: Hjalte Holm Andersen, Aalborg University

Temporal Profile of the Nociceptive Desensitization Induced by 8% Topical Capsaicin and the Functional Independence of Transient Receptor Potential Ankyrin 1 (TPRA1)- and Vanilloid 1 (TRPV1)-Expressing Nociceptive Afferents

The purpose of this study is to investigate the potential desensitising effects of repeated applications of capsaicin, trans-cinnamaldehyde and L-menthol on thermal, mechanical and chemical sensory stimulations.

Study Overview

Detailed Description

Capsaicin, the compound responsible for the pungency of chili peppers, can induce desensitization to nociceptive (1) and pruriceptive (2) stimuli when topically applied. The purpose of this study is to determine whether repeated topical applications of trans-cinnamaldehyde and L-menthol result in decreased responses to various nociceptive and non-nociceptive thermal and mechanical stimuli and to compare potential alterations with those caused by repeated topical application of capsaicin. Furthermore, this study investigates the temporal profile of said alterations.

Capsaicin 8% patches, trans-cinnamaldehyde 10%, L-menthol 40% and inert vehicle patches will each be applied to 4 4x4 cm predefined areas on the skin of the volar forearms for 1 hour 4 times on 4 consecutive days. Before each application and the day after the last application, cold detection threshold (CDT), warmth detection threshold (WDT), cold pain threshold (CPT) and heat pain threshold (HPT) will be assessed using a Medoc Pathway (Medoc, Israel) equipped with a 3x3 cm contact thermode. On the last day, mechanical detection threshold (MDT) is assessed using a series of von Frey filaments and mechanical pain threshold (MPT) and mechanical pain sensitivity (MPS) is assessed using a series of standardized pinprick stimulators (Aalborg University).

Furthermore, full-field laser perfusion imaging (FLPI) will be used to assess the degree of neurogenic inflammation in each predefined area before and after each substance application and at the last session.

  1. F. Henrich et al. 2015 "Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans"
  2. H.H. Andersen et al. 2017 "Antipruritic effect of pretreatment with 8% topical capsaicin on histamine- and cowhage-evoked itch in healthy volunteers - a randomized placebo-blinded proof-of-concept trial"

Study Type

Interventional

Enrollment (Anticipated)

22

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lars Arendt-Nielsen, Professor
  • Phone Number: 0045 99408830
  • Email: lan@hst.aau.dk

Study Locations

      • Aalborg, Denmark, 9000
        • Recruiting
        • SMI
        • Contact:
          • Hjalte H Andersen, MSc. Med.
          • Phone Number: 0045 24464515
          • Email: hha@hst.aau.dk
        • Sub-Investigator:
          • Jens B Marker, BSc. Med.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy
  • Speaks and understands English or Danish
  • 18-60 years

Exclusion Criteria:

  • Pregnancy or lactation
  • Drug addiction
  • Previous or current dermatological, neurological, musculoskeletal or mental illnesses
  • Lack of ability to cooperate
  • Current use of medications that may affect the trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Capsaicin
Capsacin (8%) patches applied topically 4 times for 1 hour to a 4x4 cm predefined area on the skin of the volar forearms.
4x4 cm patch of 8% topical capsaicin applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
Experimental: Trans-cinnamaldehyde
Trans-cinnamaldehyde (10%, dissolved in 90% ethanol) applied topically 4 times for 1 hour to a 4x4 cm predefined area on the skin of the volar forearms on a cotton ball placed in a plastic chamber to limit evaporation.
1mL of 10% trans-cinnamaldehyde applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
Experimental: L-menthol
L-menthol (40%, dissolved in 96% ethanol) applied topically 4 times for 1 hour to a 4x4 cm predefined area on the skin of the volar forearms on a cotton ball placed in a plastic chamber to limit evaporation.
1mL of 40% L-menthol applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
Placebo Comparator: Vehicle patch
Inert vehicle patches applied topically 4 times for 1 hour to a 4x4 cm predefined area on the skin of the volar forearms.
Inert vehicle patch applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cold Pain Threshold (CPT)
Time Frame: Assessed at 5 visits on 5 consecutive days
The pain threshold for cold stimulation assessed using a Medoc Pathway (Medoc, Israel) equipped with a 3x3 cm thermode. CPT is defined as the temperature at which cold induces pain and is expressed in °C.
Assessed at 5 visits on 5 consecutive days
Heat Pain Threshold (HPT)
Time Frame: Assessed at 5 visits on 5 consecutive days
The pain threshold for heat stimulation
Assessed at 5 visits on 5 consecutive days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurogenic Inflammation Intensity
Time Frame: Assessed before and after application of substances at 5 visits on 5 consecutive days
The average intensity of the neurogenic inflammation as assessed by full-field laser perfusion imaging (FLPI) (expressed in arbitrary units)
Assessed before and after application of substances at 5 visits on 5 consecutive days
Neurogenic Inflammation Area
Time Frame: Assessed before and after application of substances at 5 visits on 5 consecutive days
The area of the neurogenic inflammation as assessed by full-field laser perfusion imaging (FLPI) (expressed in arbitrary units)
Assessed before and after application of substances at 5 visits on 5 consecutive days
Pain During Application of Capsaicin
Time Frame: Assessed every 5 minutes during the 60 minute application of capsaicin at 4 visits on 4 consecutive days
Pain during the 60 minute application of topical capsaicin as rated on a visual analog scale (VAS) (0-10)
Assessed every 5 minutes during the 60 minute application of capsaicin at 4 visits on 4 consecutive days
Pain During Application of Trans-cinnamaldehyde
Time Frame: Assessed every 5 minutes during the 60 minute application of trans-cinnamaldehyde at 4 visits on 4 consecutive days
Pain during the 60 minute application of trans-cinnamaldehyde as rated on a visual analog scale (VAS) (0-10)
Assessed every 5 minutes during the 60 minute application of trans-cinnamaldehyde at 4 visits on 4 consecutive days
Pain During Application of L-menthol
Time Frame: Assessed every 5 minutes during the 60 minute application of L-menthol at 4 visits on 4 consecutive days
Pain during the 60 minute application of L-menthol as rated on a visual analog scale (VAS) (0-10)
Assessed every 5 minutes during the 60 minute application of L-menthol at 4 visits on 4 consecutive days
Pain During Application of Inert Patch (Control)
Time Frame: Assessed every 5 minutes during the 60 minute application of the inert patch (control) at 4 visits on 4 consecutive days
Pain during the 60 minute application of the inert patch (control) as rated on a visual analog scale (VAS) (0-10)
Assessed every 5 minutes during the 60 minute application of the inert patch (control) at 4 visits on 4 consecutive days
Cold Detection Threshold (CDT)
Time Frame: Assessed at 5 visits on 5 consecutive days
The detection threshold for cold stimulation assessed using a Medoc Pathway (Medoc, Israel) equipped with a 3x3 cm thermode. CDT is defined as the temperature at which cold can be detected and is expressed in °C.
Assessed at 5 visits on 5 consecutive days
Warmth Detection Threshold (WDT)
Time Frame: Assessed at 5 visits on 5 consecutive days
The detection threshold for warmth stimulation assessed using a Medoc Pathway (Medoc, Israel) equipped with a 3x3 cm thermode. WDT is defined as the temperature at which warmth can be detected and is expressed in °C.
Assessed at 5 visits on 5 consecutive days
Mechanical Detection Threshold (MDT)
Time Frame: Assessed at day 5 (final visit)
The detection threshold for mechanical stimulation is defined as the smallest force that can be felt and is assessed using a series of standardized von Frey filaments and using the "method of limits" employing a series of stimulations with ascending and descending force expressed in mN.
Assessed at day 5 (final visit)
Mechanical Pain Threshold (MPT)
Time Frame: Assessed at day 5 (final visit)
The pain threshold for mechanical stimulation is defined as the smallest force that induces pain and is assessed using a series of standardized pinprick stimulators (Aalborg University) and using the "method of limits" employing a series of stimulations with ascending and descending forces expressed in mN.
Assessed at day 5 (final visit)
Mechanical Pain Sensitivity (MPS)
Time Frame: Assessed at day 5 (final visit)
The sensitivity to mechanically induced pain induced by a series of 7 standardized pinprick stimulators (Aalborg University) as rated on a visual analog scale (VAS) ranging from 0-10 with 0 representing no pain and 10 representing the worst pain imaginable.
Assessed at day 5 (final visit)
Vibration Detection Threshold
Time Frame: Assessed at day 5 (final visit)
The detection threshold for vibrational stimulation assessed using a Vibrameter (Somedic, Sweden).
Assessed at day 5 (final visit)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

April 1, 2017

Primary Completion (Anticipated)

August 1, 2017

Study Completion (Anticipated)

August 1, 2017

Study Registration Dates

First Submitted

April 25, 2017

First Submitted That Met QC Criteria

April 25, 2017

First Posted (Actual)

April 27, 2017

Study Record Updates

Last Update Posted (Actual)

April 27, 2017

Last Update Submitted That Met QC Criteria

April 25, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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