Clinical trial NCT03132142: Desensitization of Nociceptive Afferents by Application of Topical Capsaicin, Trans-cinnamaldehyde and L-menthol
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pain
Pruritus
Neuropathic Pain
Dermatology/Skin - Other
Lead sponsor: Aalborg University
Sponsor class: OTHER
First posted: 2017-04-27
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

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"

Eligibility criteria: 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

Primary outcomes:
measure: Cold Pain Threshold (CPT)
timeFrame: Assessed at 5 visits on 5 consecutive days
measure: Heat Pain Threshold (HPT)
timeFrame: Assessed at 5 visits on 5 consecutive days
Secondary outcomes:
measure: Neurogenic Inflammation Intensity
timeFrame: Assessed before and after application of substances at 5 visits on 5 consecutive days
measure: Neurogenic Inflammation Area
timeFrame: Assessed before and after application of substances at 5 visits on 5 consecutive days
measure: Pain During Application of Capsaicin
timeFrame: Assessed every 5 minutes during the 60 minute application of capsaicin at 4 visits on 4 consecutive days
measure: Pain During Application of Trans-cinnamaldehyde
timeFrame: Assessed every 5 minutes during the 60 minute application of trans-cinnamaldehyde at 4 visits on 4 consecutive days
measure: Pain During Application of L-menthol
timeFrame: Assessed every 5 minutes during the 60 minute application of L-menthol at 4 visits on 4 consecutive days
measure: Pain During Application of Inert Patch (Control)
timeFrame: Assessed every 5 minutes during the 60 minute application of the inert patch (control) at 4 visits on 4 consecutive days
measure: Cold Detection Threshold (CDT)
timeFrame: Assessed at 5 visits on 5 consecutive days
measure: Warmth Detection Threshold (WDT)
timeFrame: Assessed at 5 visits on 5 consecutive days
measure: Mechanical Detection Threshold (MDT)
timeFrame: Assessed at day 5 (final visit)
measure: Mechanical Pain Threshold (MPT)
timeFrame: Assessed at day 5 (final visit)
measure: Mechanical Pain Sensitivity (MPS)
timeFrame: Assessed at day 5 (final visit)
measure: Vibration Detection Threshold
timeFrame: Assessed at day 5 (final visit)
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: SMI
Study officials:
References: