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

Not Applicable
Conditions
Pain
Pruritus
Dermatology/Skin - Other
Neuropathic Pain
Interventions
Registration Number
NCT03132142
Lead Sponsor
Aalborg University
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"

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
22
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
CapsaicinCapsaicinCapsacin (8%) patches applied topically 4 times for 1 hour to a 4x4 cm predefined area on the skin of the volar forearms.
Vehicle patchVehicle patchInert vehicle patches applied topically 4 times for 1 hour to a 4x4 cm predefined area on the skin of the volar forearms.
Trans-cinnamaldehydeTrans-cinnamaldehydeTrans-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.
L-mentholL-MentholL-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.
Primary Outcome Measures
NameTimeMethod
Cold Pain Threshold (CPT)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.

Heat Pain Threshold (HPT)Assessed at 5 visits on 5 consecutive days

The pain threshold for heat stimulation

Secondary Outcome Measures
NameTimeMethod
Pain During Application of Inert Patch (Control)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)

Pain During Application of CapsaicinAssessed 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)

Pain During Application of Trans-cinnamaldehydeAssessed 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)

Vibration Detection ThresholdAssessed at day 5 (final visit)

The detection threshold for vibrational stimulation assessed using a Vibrameter (Somedic, Sweden).

Neurogenic Inflammation IntensityAssessed 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)

Neurogenic Inflammation AreaAssessed 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)

Cold Detection Threshold (CDT)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.

Pain During Application of L-mentholAssessed 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)

Warmth Detection Threshold (WDT)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.

Mechanical Detection Threshold (MDT)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.

Mechanical Pain Threshold (MPT)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.

Mechanical Pain Sensitivity (MPS)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.

Trial Locations

Locations (1)

SMI

🇩🇰

Aalborg, Denmark

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