Dermatology/Skin - Other, Neuropathic Pain, Pain, Pruritus
Conditions
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
Interventions
DRUGCapsaicin
4x4 cm patch of 8% topical capsaicin applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
DRUGTrans-cinnamaldehyde
1mL of 10% trans-cinnamaldehyde applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
DRUGL-Menthol
1mL of 40% L-menthol applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
DRUGVehicle patch
Inert vehicle patch applied to the skin of the volar forearm for 1 hour 4 times on 4 consecutive days
Sponsors
Aalborg University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Pain During Application of Capsaicin | 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) |
| Pain During Application of Trans-cinnamaldehyde | 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) |
| Pain During Application of L-menthol | 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) |
| 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) |
| 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. |
| Neurogenic Inflammation Intensity | 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) |
| 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. |
| Vibration Detection Threshold | Assessed at day 5 (final visit) | The detection threshold for vibrational stimulation assessed using a Vibrameter (Somedic, Sweden). |
| 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. |
| Neurogenic Inflammation Area | 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) |
Countries
Denmark
Contacts
Primary ContactLars Arendt-Nielsen, Professor
Outcome results
None listed