The Effect of Halophyte-based Cream on Pain and Itch

Effects of Halophyte-based Cream Skin Application in a Human Experimental Model of Pain and Itch

In this study the investigators wish to investigate whether halophyte-based cream applied to the skin can reduce itch applied by means of small needles from the plant mucuna pruriens (also called cowhage) or by histamine (an itch-evoking substance formed in the human body). Further, the investigators wishes to investigate whether long-term application of halophyte-based cream has a pain-relieving effect on heat/cold and pinprick stimulations.

Study Overview

• Status: Completed
• Conditions: Pain, Acute; Itch
• Intervention / Treatment: Other: Histamine 1%; Other: Halophites-based cream 24 hours; Other: Vehicle cream 24 hours; Other: Cowhage; Other: Halophites-based cream 48 hours; Other: Vehicle cream 48 hours

Detailed Description

Salt-tolerant plants (also called halophytes) can grow in saline soil or directly in salt water (e.g. along coasts). For centuries, these plants have been used in folk medicine, and among other things they are believed to have pain-relieving and anti-inflammatory effect.

Even though experiments have already investigated halophytes as a pain relieving substance, the mechanisms in relation to pain and/or itch are still unknown. Therefore, the investigators wish to investigate whether halophyte-based cream applied to the skin can reduce itch applied by means of small needles from the plant mucuna pruriens (also called cowhage) or by histamine (an itch-evoking substance formed in the human body). Further, the investigators wishes to investigate whether long-term application of halophyte-based cream has a pain-relieving effect on heat/cold and pinprick stimulations.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 neurologic, musculoskeletal or mental illnesses that may affect the results (e.g. neuropathy, muscular pain in the upper extremities, etc.)
• Lack of ability to cooperate
• Current use of medications that may affect the trial such as antihistamine medications or pain killers
• Skin diseases
• Consumption of alcohol or painkillers 24 hours before the study days and between these
• Acute or chronic pain
• Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical trials)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Halophites-based cream 24 hours; A 2 gram amount of Halophites-based cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.	Other: Histamine 1%; To deliver histamine, standard allergy skin prick test (SPT) lancets are applied. The lancets have a 1 mm shouldered tip adapt to introduce a small amount of test substance extremely locally and approximately at the dermo-epidermal junction.; Other: Halophites-based cream 24 hours; The concentration of active aqueous extract will be in the range of 2% to 30% (v/v) by cold emulsification. A 2 gram amount of Halophytes-based cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.; Other: Vehicle cream 24 hours; A 2 gram amount of vehicle cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.; Other: Cowhage; The insertion of cowhage spicule(s) rapidly and consistently produces itch with no or very little flare reaction. This insertion is conducted by forceps using a stereo-microscope, and 30-35 spicules are gently rubbed into a 1 cm diameter skin area.
Active Comparator: Halophites-based cream 48 hours; A 2 gram amount of Halophites-based cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.	Other: Histamine 1%; To deliver histamine, standard allergy skin prick test (SPT) lancets are applied. The lancets have a 1 mm shouldered tip adapt to introduce a small amount of test substance extremely locally and approximately at the dermo-epidermal junction.; Other: Cowhage; The insertion of cowhage spicule(s) rapidly and consistently produces itch with no or very little flare reaction. This insertion is conducted by forceps using a stereo-microscope, and 30-35 spicules are gently rubbed into a 1 cm diameter skin area.; Other: Halophites-based cream 48 hours; The concentration of active aqueous extract will be in the range of 2% to 30% (v/v) by cold emulsification. A 2 gram amount of Halophytes-based cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.; Other: Vehicle cream 48 hours; A 2 gram amount of vehicle cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Superficial blood perfusion	Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).	Day 0
Superficial blood perfusion	Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).	24 hours after cream application
Superficial blood perfusion	Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).	48 hours after cream application
Itch intensity	The subject will rate the itch sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no itch and "100" worst itch imaginable	Day 0
Itch intensity	The subject will rate the itch sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no itch and "100" worst itch imaginable	24 hours after cream application
Itch intensity	The subject will rate the itch sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no itch and "100" worst itch imaginable	48 hours after cream application
Pain intensity	The subject will rate the pain sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no pain and "100" worst pain imaginable	Day 0
Pain intensity	The subject will rate the pain sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no pain and "100" worst pain imaginable	24 hours after cream application
Pain intensity	The subject will rate the pain sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no pain and "100" worst pain imaginable	48 hours after cream application
Measuring Alloknesis	Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).	Day 0
Measuring Alloknesis	Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).	24 hours after cream application
Measuring Alloknesis	Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).	48 hours after cream application
Trans-epidermal Water Loss (TEWL)	TEWL is a non-invasive and pain free measuring technique in which a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These collectively establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.	Day 0
Trans-epidermal Water Loss (TEWL)	TEWL is a non-invasive and pain free measuring technique in which a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These collectively establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.	24 hours after cream application
Trans-epidermal Water Loss (TEWL)	TEWL is a non-invasive and pain free measuring technique in which a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These collectively establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.	48 hours after cream application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Warm Detection Thresholds (WDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (warm sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	Day 0
Measurement of Warm Detection Thresholds (WDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (warm sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	24 hours after cream application
Measurement of Warm Detection Thresholds (WDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (warm sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	48 hours after cream application
Measurement of Cold Detection Thresholds (CDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (cold sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	Day 0
Measurement of Cold Detection Thresholds (CDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (cold sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	24 hours after cream application
Measurement of Cold Detection Thresholds (CDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (cold sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	48 hours after cream application
Measurement of Heat Pain Thresholds (HPT)	The tests for thermal sensation will all be performed using the same PATHWAY ATS thermal sensory testing device as above. The stimulations are again applied on the treated/placebo areas. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	Day 0
Measurement of Heat Pain Thresholds (HPT)	The tests for thermal sensation will all be performed using the same PATHWAY ATS thermal sensory testing device as above. The stimulations are again applied on the treated/placebo areas. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	24 hours after cream application
Measurement of Heat Pain Thresholds (HPT)	The tests for thermal sensation will all be performed using the same PATHWAY ATS thermal sensory testing device as above. The stimulations are again applied on the treated/placebo areas. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	48 hours after cream application
Measurement of Cold Pain Thresholds (CPT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	Day 0
Measurement of Cold Pain Thresholds (CPT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	24 hours after cream application
Measurement of Cold Pain Thresholds (CPT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	48 hours after cream application
Measurement of Pain to Supra-threshold Heat Stimuli:	Again, the tests will be performed by using the PATHWAY ATS thermal sensory testing device. The subjects will have to rate the pain to three suprathreshold heat pain stimuli (starting and ending at 34°C with an increase and decrease of 5°C and 4 s plateau at 50°C) applied on the treated/placebo areas .	Day 0
Measurement of Pain to Supra-threshold Heat Stimuli:	Again, the tests will be performed by using the PATHWAY ATS thermal sensory testing device. The subjects will have to rate the pain to three suprathreshold heat pain stimuli (starting and ending at 34°C with an increase and decrease of 5°C and 4 s plateau at 50°C) applied on the treated/placebo areas .	24 hours after cream application
Measurement of Pain to Supra-threshold Heat Stimuli:	Again, the tests will be performed by using the PATHWAY ATS thermal sensory testing device. The subjects will have to rate the pain to three suprathreshold heat pain stimuli (starting and ending at 34°C with an increase and decrease of 5°C and 4 s plateau at 50°C) applied on the treated/placebo areas .	48 hours after cream application
Measurement of Mechanical Pain Thresholds (MPT)	This test is performed using a pin-prick set (Aalborg University, Aalborg). The set consists of 8 needles each having a diameter of 0.6 mm and different force applications: 0.8, 1.6, 3.2, 6.4, 12.8, 25.6, 50.1 and 60.0 g. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order until the first perception of sharpness is reached. The final threshold is the geometric mean of five series of ascending and descending stimuli.	Day 0
Measurement of Mechanical Pain Thresholds (MPT)	This test is performed using a pin-prick set (Aalborg University, Aalborg). The set consists of 8 needles each having a diameter of 0.6 mm and different force applications: 0.8, 1.6, 3.2, 6.4, 12.8, 25.6, 50.1 and 60.0 g. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order until the first perception of sharpness is reached. The final threshold is the geometric mean of five series of ascending and descending stimuli.	24 hours after cream application
Measurement of Mechanical Pain Thresholds (MPT)	This test is performed using a pin-prick set (Aalborg University, Aalborg). The set consists of 8 needles each having a diameter of 0.6 mm and different force applications: 0.8, 1.6, 3.2, 6.4, 12.8, 25.6, 50.1 and 60.0 g. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order until the first perception of sharpness is reached. The final threshold is the geometric mean of five series of ascending and descending stimuli.	48 hours after cream application
Measurement of Mechanical Pain Sensitivity (MPS)	This test is performed using the same pin-prick set as for the MPT test. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order, and the subject will be asked to give a pain rating for each stimulus on a scale from 0-10 (where 0 indicates ''no pain'', and 10 indicates the ''worst imaginable pain''). This procedure will be repeated twice.	Day 0
Measurement of Mechanical Pain Sensitivity (MPS)	This test is performed using the same pin-prick set as for the MPT test. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order, and the subject will be asked to give a pain rating for each stimulus on a scale from 0-10 (where 0 indicates ''no pain'', and 10 indicates the ''worst imaginable pain''). This procedure will be repeated twice.	24 hours after cream application
Measurement of Mechanical Pain Sensitivity (MPS)	This test is performed using the same pin-prick set as for the MPT test. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order, and the subject will be asked to give a pain rating for each stimulus on a scale from 0-10 (where 0 indicates ''no pain'', and 10 indicates the ''worst imaginable pain''). This procedure will be repeated twice.	48 hours after cream application

Collaborators and Investigators

• Sponsor: Aalborg University

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: October 28, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine Agents; Histamine Agonists; Histamine
• Other Study ID Numbers: N-20200072

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No