Itch
Conditions
Brief summary
Chronic itch affects approximately a fifth of the global population and is associated with substantial negative consequences for the affected individuals. Furthermore, there is a lack of efficient treat-ment options for chronic itch. Topical ketamine cream has been used successfully to relieve various forms of pain, and we hypothesize that topical ketamine relieves itch through a mechanism of action comparable to that in pain relief. The aim of this project is to evaluate the effects of ketamine both alone and in combination with amitriptyline on histaminergic and non-histaminergic itch induced by histamine and cowhage, respectively.
Detailed description
The main action of ketamine, 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone, is to antagonize the glutamate N-methyl-D-aspartate (NMDA) receptors. In the clinical setting, topical ketamine cream has been used successfully to relieve various pathogenic forms of pain. In addition to its pain-relieving effects, the cream was also reported to have itch-relieving properties in a very limited study. However, its efficacy on itch has not been established, and the mechanism of action remains uncertain. Ketamine cream is used not only by itself, but also in conjunction with other analgesics. One of these is amitriptyline, which may enhance the analgesic effects of ketamine. The aim of this human experimental study is to use the well-characterized anesthetic Ketamine, both alone and in combination with amitriptyline, as a tool to modulate different histaminergic and non-histaminergic itch modalities evoked by histamine and cowhage.
Interventions
DRUGKetamine 0.5%
Ketamine cream 0.5% will be applied in a 4x4 area in the forearm of each participant.
DRUGAmitriptyline
Amitriptyline cream 1% will be applied in a 4x4 area in the forearm of each participant.
DRUGketamine + amitriptyline
A cream containing ketamine 0.5%, amitriptyline 1%, will be applied in a 4x4 area in the forearm of each participant.
OTHERVehicle
A vehicle cream will be applied in a 4x4 area in the forearm of each participant.
OTHERHistamine
After the cream removal, itch will be induced using histamine in the first session
OTHERCowhage
After the cream removal, itch will be induced using cowhage in the second session
Sponsors
Aalborg University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
The participant will be blinded about which cream is applied.
Intervention model description
In each participant, the four different creams will be applied in a randomized position. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men and women * 18-60 years * Speak and understand English
Exclusion criteria
* Pregnancy or lactation * Drug addiction defined as any use of cannabis, opioids, or other drugs * Previous or current history of neurological, dermatological, immunological, musculoskeletal, cardiac disorder or mental illnesses (psychiatric diagnosis) that may affect the results (e.g., neuropathy, muscular pain in the upper extremities, anxiety, depression, schizophrenia etc.) * Moles, wounds, scars, or tattoos in the area to be treated or tested * Current use of medications that may affect the trial such as antihistamines and pain killers. * Participants had known allergy/discomfort to ketamine or amitriptyline * Skin diseases * Consumption of alcohol or painkillers 24 hours before the study days and between these * Acute or chronic pain and itch * Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical studies) * Lack of ability to cooperate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measuring itch by computerized Visual Analog Scale Scoring | Immediately after the intervention | We will ask the subjects to rate the sensation of itch on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates no itch and 100 indicates worst itch imaginable. |
| Measuring pain by computerized Visual Analog Scale Scoring | Immediately after the intervention | We will ask the subjects to rate the sensation of pain on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates no pain and 100 indicates worst pain imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mechanically evoked itch (MEI), intensity approach | Immediately after the intervention | MEI is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force). |
| Mechanically evoked itch, spatial approach | Immediately after the intervention | The von-Frey filament that better evokes the itch sensation during the assessment of mechanically evoked itch as well as a template of soft plastic are used to map the area of hyperkinesis in the test areas (forearms). |
| Mechanical Pain Thresholds (MPT) | Immediately after the intervention | This test is conducted using a pinprick set. The set consists of 7 needles each with a diameter of 0.6 mm and different force applications: 8, 16, 32, 64, 128, 256, and 512 mN. |
| Mechanical Pain Sensitivity (MPS), intensity approach | Immediately after the intervention | This test is conducted with the same pinprick set used to test the MPT. |
| Mechanical Pain Sensitivity (MPS), spatial approach | Immediately after the intervention | The pinprick that was selected in the MPT as well as a template of soft plastic are used to map the area of hyperalgesia in the test areas (forearms). |
| Superficial blood perfusion | Immediately after the intervention | Superficial blood perfusion (SBP) is measured by a Speckle contrast imager |
| Warm Detection Thresholds (WDT) | Immediately after the intervention | The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device |
| Cold Pain Thresholds (CPT) | Immediately after the intervention | The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device |
| Heat Pain Thresholds (HPT) | Immediately after the intervention | The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device |
| Pain to Supra-threshold Heat Stimuli (STHS) | Immediately after the intervention | The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device |
| Cold Detection Thresholds (CDT) | Immediately after the intervention | The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device |
| Touch Pleasantness | Immediately after the intervention | Pleasant touch sensation measured using a standardized sensory brush exerting a force of 200 to 400 mN. |
Countries
Denmark
Outcome results
None listed