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The use of topical over-the-counter (OTC) products with a warming or cooling effect is widespread in the fields of sport, physiotherapy and in private households. Advertisements for such products promise pain relief when suffering from musculoskeletal disorders such as muscle tension, rheumatism or acute injuries, e.g. sprains. In literature, there are only little information about the efficacy and the physiological mechanisms of topical warming or cooling products. Therefore, the aim of this study is to investigate the local skin characteristics during and after an application of a topical product with a warming or cooling effect.
The use of topical products for local pain relief in chronic or acute musculoskeletal disorders is widely used. Despite the widespread use of these products, there is missing information on the physiological mechanisms and efficacy of topical warming and cooling ointments. Most of the existing literature is about the efficacy of topical non-steroidal anti-inflammatory drug (NSAID)-products on chronic pain in osteoarthritis. Furthermore, one study tested the cooling effect of gels with different menthol concentrations. They found that, regardless of the concentration, the skin temperature was reduced up to one hour post application in the area of application.
The aim of our study is to evaluate the change of skin characteristics after a single application of a warming or cooling topical product on healthy subjects. Outcome parameters include skin perfusion, temperature, skin redness and subjective thermal sensation. We only selected products in form of alcohol based ointments, menthol or wintergreen oil. Sprays and patches were excluded.
The application area is the unilateral lumbar back region, whereas the contralateral side serves as control area. After an acclimatization period, baseline measurements are performed, followed by standardized application of the topical product. The local skin responses are measured in 10 mins time increments up to one hour.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Axanova hot gel | Experimental | Intervention: Axanova hot gel is a topical product with a warming effect. In a single application 3g of the product is applied in an area of 10cm x 10cm on the unilateral lumbar back until it has been completely absorbed by the skin. |
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| Axanova hot gel control | No Intervention | No product application. The contralateral lumbar back side acts as a Axanova hot gel control. | |
| Axanova activ gel | Experimental | Intervention: Axanova activ gel is a topical product with a revulsive effect. In a single application 3g of the product is applied in an area of 10cm x 10cm on the unilateral lumbar back until it has been completely absorbed by the skin. |
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| Axanova activ gel control | No Intervention | No product application. The contralateral lumbar back side acts as a Axanova activ gel control. | |
| Perskindol Dolo Gel | Experimental | Intervention: Perskindol Dolo Gel is a topical product with a warming effect. In a single application 3g of the product is applied in an area of 10cm x 10cm on the unilateral lumbar back until it has been completely absorbed by the skin. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Axanova hot gel | Other | Axanova hot gel is a topical product with a warming effect. It contains menthol, pine needle oil, wintergreen oil, rosemary oil, eucalyptus oil, incense oil. |
| Measure | Description | Time Frame |
|---|---|---|
| Local Skin Perfusion | Local skin perfusion was measured with laser speckle contrast imaging (LSCI). The LSCI system uses arbitrary units to express the mean flux in the specified regions of interest which is related to the concentration of circulating erythrocytes in the tissue sample volume, scaled from blue (low perfusion) to red (high perfusion). | during 45min post application |
| Skin Surface Temperature | skin surface temperature will be measured with thermochrons, infrared thermometer and thermal imaging camera | At baseline and during 45 minutes post application |
| Local Muscle Tissue Oxygenation | local muscle tissue oxygenation will be measured with near infrared spectroscopy | At baseline and during 45 min post application |
| Subjective Temperature Sensation | Thermal sensation ("How does this feel like?") was assessed in each skin area according to the ISO 10551 standard using the following 9-point Likert scale: 4 = very hot, 3 = hot, 2 = warm, 1 = slightly warm, 0 = neutral,-1 = slightly cool,-2 = cool,-3 = cold,-4 = very cold. | At baseline and during 45 minutes post application |
| Subjective Thermal Comfort | Thermal comfort was assessed ("Do you find this. . .?") in each skin area according to the ISO 10551 standard using using a 5-point Likert scale with 0 = comfortable, 1 = slightly uncomfortable, 2 = uncomfortable, 3 = very uncomfortable, 4 = extremely uncomfortable. | At baseline and during 45 minutes post application |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ron Clijsen, PhD | University of Applied Sciences and Arts of Southern Switzerland (SUPSI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| SUPSI | Landquart | Kanton Graubünden | CH-7302 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38706945 | Result | Versteeg N, Wellauer V, Wittenwiler S, Aerenhouts D, Clarys P, Clijsen R. Short-term cutaneous vasodilatory and thermosensory effects of topical methyl salicylate. Front Physiol. 2024 Apr 19;15:1347196. doi: 10.3389/fphys.2024.1347196. eCollection 2024. |
| Label | URL |
|---|---|
| fullversion of publication | View source |
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The project originally planned to include several comparative experiments. However, due to personal and financial constraints, only one experiment was completed by the end of the study period. Owing to competing academic priorities, the study was not extended and was therefore concluded at that point.
A total of 21 healthy women were recruited. On each participant, two skin areas (5 cm × 10 cm) were marked on either side of the thoracic spine. Methyl salicylate gel was applied to one side, while a placebo gel was applied simultaneously to the opposite side. Thus, this was a "split-person" design, with each participant serving as her own control.
| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Women Receiving Topical Application of Methyl Salicylate and Placebo Gels | Healthy women participated. Two adjacent skin areas were marked on the thoracic spine (Th4-Th7). On one side, a methyl salicylate gel (Perskindol Dolo Gel-based formulation) was applied; on the other side, a placebo gel was applied. Methyl salicylate gel composition: natural wintergreen oil (12.9%), hydroxyethyl cellulose (5%), water, methyl parahydroxybenzoate, propyl parahydroxybenzoate, and propylene glycol. Placebo gel composition: hydroxyethyl cellulose, water, methyl parahydroxybenzoate, propyl parahydroxybenzoate, and propylene glycol. The placebo gel differed only by the absence of natural wintergreen oil. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 24, 2019 |
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| Perskindol Dolo Gel control | No Intervention | No product application. The contralateral lumbar back side acts as a Perskindol Dolo Gel control. |
| Perskindol Classic Gel | Experimental | Intervention: Perskindol Classic Gel is a topical product with a revulsive effect. In a single application 3g of the product is applied in an area of 10cm x 10cm on the unilateral lumbar back until it has been completely absorbed by the skin. |
|
| Perskindol Classic Gel control | No Intervention | No product application. The contralateral lumbar back side acts as a Perskindol Classic Gel control. |
| Perskindol Cool Kühl-Gel | Experimental | Intervention: Perskindol Cool Kühl-Gel is a topical product with a cooling effect. In a single application 3g of the product is applied in an area of 10cm x 10cm on the unilateral lumbar back until it has been completely absorbed by the skin. |
|
| Perskindol Cool Kühl-Gel control | No Intervention | No product application. The contralateral lumbar back side acts as a Perskindol Cool Kühl-Gel control. |
| Dolor-X Hot Gel | Experimental | Intervention: Dolor-X Hot Gel is a topical product with a warming effect. In a single application 3g of the product is applied in an area of 10cm x 10cm on the unilateral lumbar back until it has been completely absorbed by the skin. |
|
| Dolor-X Hot Gel control | No Intervention | No product application. The contralateral lumbar back side acts as a Dolor-X Hot Gel control. |
| Dolor-X Classic Gel | Experimental | Intervention: Dolor-X Classic Gel is a topical product with a revulsive effect. In a single application 3g of the product is applied in an area of 10cm x 10cm on the unilateral lumbar back until it has been completely absorbed by the skin. |
|
| Dolor-X Classic Gel control | No Intervention | No product application. The contralateral lumbar back side acts as a Dolor-X Classic Gel control. |
| Dolor-X Cool Gel | Experimental | Intervention: Dolor-X Cool Gel is a topical product with a cooling effect. In a single application 3g of the product is applied in an area of 10cm x 10cm on the unilateral lumbar back until it has been completely absorbed by the skin. |
|
| Dolor-X Cool Gel control | No Intervention | No product application. The contralateral lumbar back side acts as a Dolor-X Cool Gel control. |
| Axanova activ gel | Other | Axanova activ gel is a topical product with a revulsive effect. It contains menthol, pine needle oil, orange oil, lemon oil, wintergreen oil, glycosaminoglycans. |
|
| Perskindol Dolo Gel | Other | Perskindol Dolo Gel is a topical product with a warming effect. It contains wintergreen oil, pine needle oil, aromatics, excipients. |
|
| Perskindol Classic Gel | Other | Perskindol Classic Gel is a topical product with a revulsive effect. It contains menthol, wintergreen oil, pine needle oil, lemon oil, orange peel oil, lemon bergamot oil, rosemary oil, lavender oil, excipients. |
|
| Perskindol Cool Kühl-Gel | Other | Perskindol Cool Kühl-Gel is a topical product with a cooling effect. It contains levomenthol, color E131, aromatics, excipients. |
|
| Dolor-X Hot Gel | Other | Dolor-X Hot Gel is a topical product with a warming effect. It contains isopropyl alcohol, water, menthol, hyprolose, camphor, trometamol, paprika, wintergreen oil, excipients. |
|
| Dolor-X Classic Gel | Other | Dolor-X Classic Gel is a revulsive product. It contains water, isopropyl alcohol, menthol, spruce, hyprolose, trometamol, wintergreen oil, excipients. |
|
| Dolor-X Cool Gel | Other | Dolor-X Cool Gel is a cooling product. It contains water, isopropyl alcohol, menthol, trometamol, color E131, excipients. |
|
| Methyl Salicylate Gel |
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| Placebo Gel |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Women Receiving Topical Application of Methyl Salicylate and Placebo Gels | Healthy women participated. Two adjacent skin areas were marked on the thoracic spine (Th4-Th7). On one side, a methyl salicylate gel (Perskindol Dolo Gel-based formulation) was applied; on the other side, a placebo gel was applied. Methyl salicylate gel composition: natural wintergreen oil (12.9%), hydroxyethyl cellulose (5%), water, methyl parahydroxybenzoate, propyl parahydroxybenzoate, and propylene glycol. Placebo gel composition: hydroxyethyl cellulose, water, methyl parahydroxybenzoate, propyl parahydroxybenzoate, and propylene glycol. The placebo gel differed only by the absence of natural wintergreen oil. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Local Skin Perfusion | Local skin perfusion was measured with laser speckle contrast imaging (LSCI). The LSCI system uses arbitrary units to express the mean flux in the specified regions of interest which is related to the concentration of circulating erythrocytes in the tissue sample volume, scaled from blue (low perfusion) to red (high perfusion). | 21 participants received methyl salicylate gel on a 5 cm × 10 cm skin area on one side of the thoracic spine and placebo gel on the other side; the side was randomized. | Posted | Mean | Standard Deviation | % of baseline MCskin | during 45min post application |
|
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| Primary | Skin Surface Temperature | skin surface temperature will be measured with thermochrons, infrared thermometer and thermal imaging camera | 21 participants received methyl salicylate gel on a 5 cm × 10 cm skin area on one side of the thoracic spine and placebo gel on the other side; the side was randomized. | Posted | Mean | Standard Deviation | degrees Celsius | At baseline and during 45 minutes post application |
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| Primary | Local Muscle Tissue Oxygenation | local muscle tissue oxygenation will be measured with near infrared spectroscopy | 21 participants received methyl salicylate gel on a 5 cm × 10 cm skin area on one side of the thoracic spine and placebo gel on the other side; the side was randomized. | Posted | Mean | Standard Deviation | % SmO2 | At baseline and during 45 min post application |
|
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| Primary | Subjective Temperature Sensation | Thermal sensation ("How does this feel like?") was assessed in each skin area according to the ISO 10551 standard using the following 9-point Likert scale: 4 = very hot, 3 = hot, 2 = warm, 1 = slightly warm, 0 = neutral,-1 = slightly cool,-2 = cool,-3 = cold,-4 = very cold. | 21 participants received methyl salicylate gel on a 5 cm × 10 cm skin area on one side of the thoracic spine and placebo gel on the other side; the side was randomized. | Posted | Count of Participants | Participants | At baseline and during 45 minutes post application |
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| Primary | Subjective Thermal Comfort | Thermal comfort was assessed ("Do you find this. . .?") in each skin area according to the ISO 10551 standard using using a 5-point Likert scale with 0 = comfortable, 1 = slightly uncomfortable, 2 = uncomfortable, 3 = very uncomfortable, 4 = extremely uncomfortable. | 21 participants received methyl salicylate gel on a 5 cm × 10 cm skin area on one side of the thoracic spine and placebo gel on the other side; the side was randomized. | Posted | Count of Participants | Participants | At baseline and during 45 minutes post application |
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Adverse events were assessed throughout the laboratory visit, lasting approximately 1 hour (45min post application).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Methyl Salicylate | A gel, custom-made by a pharmacy based on the formulation found in Perskindol Dolo Gel, was applied to the skin area on the thoracic spine (Th4-Th7). The methyl salicylate gel consisted of natural wintergreen oil (12.9%), hydroxyethyl cellulose (5%), water, methyl parahydroxybenzoate, propyl parahydroxybenzoate, propylene glycol. | 0 | 21 | 0 | 21 | 0 | 21 |
| EG001 | Control | A placebo gel was applied to the skin over the thoracic spine (Th4-Th7). The placebo gel consisted of hydroxyethyl cellulose, water, methyl parahydroxybenzoate, propyl parahydroxybenzoate, and propylene glycol, and differed from the methyl salicylate gel by the absence of natural wintergreen oil. | 0 | 21 | 0 | 21 | 0 | 21 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ron Clijsen | Rehabilitation and Exercise Science Laboratory (RESlab), University of Applied Sciences and Arts of Southern Switzerland | 0041 81 300 01 78 | ron.clijsen@supsi.ch |
| Aug 21, 2025 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D006940 | Hyperemia |
| D004890 | Erythema |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Title | Measurements |
|---|---|
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| Methyl salicylate: T15 |
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| Methyl salicylate: T20 |
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| Methyl salicylate: T25 |
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| Methyl salicylate: T30 |
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| Methyl salicylate: T35 |
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| Methyl salicylate: T40 |
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| Methyl salicylate: T45 |
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| Placebo gel: T0 |
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| Placebo gel: T5 |
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| Placebo gel: T10 |
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| Placebo gel: T15 |
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| Placebo gel: T20 |
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| Placebo gel: T25 |
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| Placebo gel: T30 |
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| Placebo gel: T35 |
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| Placebo gel: T40 |
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| Placebo gel: T45 |
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