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

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03132142
• Other study ID #: N-20170018
• Status: Recruiting
• Phase: N/A
• First received: April 25, 2017
• Last updated: April 25, 2017
• Start date: April 2017
• Est. completion date: August 2017

Study information

• Verified date: April 2017
• Source: Aalborg University
• Contact: Lars Arendt-Nielsen, Professor
• Phone: 0045 99408830
• Email: lan[@]hst.aau.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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"

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 22
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Dermatology/Skin - Other
• Neuralgia
• Neuropathic Pain
• Pain
• Pruritus

Intervention

Drug:
• Capsaicin
4x4 cm patch of 8% topical capsaicin applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
• Trans-cinnamaldehyde
1mL of 10% trans-cinnamaldehyde applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
• L-Menthol
1mL of 40% L-menthol applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
• Vehicle patch
Inert vehicle patch applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days

Locations

Country	Name	City	State
Denmark	SMI	Aalborg

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cold Pain Threshold (CPT)	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
Primary	Heat Pain Threshold (HPT)	The pain threshold for heat stimulation	Assessed at 5 visits on 5 consecutive days
Secondary	Neurogenic Inflammation Intensity	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
Secondary	Neurogenic Inflammation Area	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
Secondary	Pain During Application of Capsaicin	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
Secondary	Pain During Application of Trans-cinnamaldehyde	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
Secondary	Pain During Application of L-menthol	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
Secondary	Pain During Application of Inert Patch (Control)	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
Secondary	Cold Detection Threshold (CDT)	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
Secondary	Warmth Detection Threshold (WDT)	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
Secondary	Mechanical Detection Threshold (MDT)	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)
Secondary	Mechanical Pain Threshold (MPT)	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)
Secondary	Mechanical Pain Sensitivity (MPS)	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)
Secondary	Vibration Detection Threshold	The detection threshold for vibrational stimulation assessed using a Vibrameter (Somedic, Sweden).	Assessed at day 5 (final visit)