Clinical trial NCT02653703: L-menthol as a Topical Counter-irritant to TRPA1-induced Neurogenic Inflammation and Pain
Official title: High-concentration L-menthol as a Counter-irritant to TRPA1-induced Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Inflammation
Pruritus
Hyperalgesia
Lead sponsor: Aalborg University
Sponsor class: OTHER
First posted: 2016-01-12
Enrollment: 14
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of this study is to quantitatively characterize the effects of L-menthol as a topical counter-irritant on cutaneous pain and hyperalgesia provoked by topical application of the TRPA1-agonist trans-cinnamaldehyde (CA) in healthy human volunteers.

Detailed description: This study is designed as an experimental model in healthy humans.

Eligibility criteria: Inclusion Criteria:

* 18 healthy men and women aged 18-50 years willing to abstain from alcohol, nicotine, caffeine and pain medication 24 hours before experimental sessions

Exclusion Criteria:

* Pregnancy
* Skin disorders (e.g. contact eczema)
* Chronic pain conditions
* Drug addiction defined as the use of cannabis, opioids or other drugs
* Previous neurologic, musculoskeletal or mental illnesses
* Lack of ability to cooperate

Primary outcomes:
measure: Spontaneous pain intensity [self-reported on a visual analog scale]
timeFrame: 0-20 minutes with a sampling frequency of 1/1 min
Secondary outcomes:
measure: Neurogenic inflammation [Measured by Laser speckle flowmetry in a 3x3 cm area]
timeFrame: 20-25 minutes post induction
measure: Heat hyperalgesia
timeFrame: 25-27.5 minutes post induction
measure: Mechanical hyperalgesia
timeFrame: 27.5-30 minutes post induction
Other outcomes:
Locations:
Study officials:
References:
citation: Olsen RV, Andersen HH, Moller HG, Eskelund PW, Arendt-Nielsen L. Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM8 and TRPA1 using topical L-menthol and trans-cinnamaldehyde in healthy volunteers. Eur J Pain. 2014 Oct;18(9):1333-42. doi: 10.1002/j.1532-2149.2014.494.x. Epub 2014 Mar 25.
citation: Hojland CR, Andersen HH, Poulsen JN, Arendt-Nielsen L, Gazerani P. A human surrogate model of itch utilizing the TRPA1 agonist trans-cinnamaldehyde. Acta Derm Venereol. 2015 Sep;95(7):798-803. doi: 10.2340/00015555-2103.
citation: Namer B, Seifert F, Handwerker HO, Maihofner C. TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. Neuroreport. 2005 Jun 21;16(9):955-9. doi: 10.1097/00001756-200506210-00015.
citation: Namer B, Kleggetveit IP, Handwerker H, Schmelz M, Jorum E. Role of TRPM8 and TRPA1 for cold allodynia in patients with cold injury. Pain. 2008 Sep 30;139(1):63-72. doi: 10.1016/j.pain.2008.03.007. Epub 2008 Apr 25.
citation: Andersen HH, Olsen RV, Moller HG, Eskelund PW, Gazerani P, Arendt-Nielsen L. A review of topical high-concentration L-menthol as a translational model of cold allodynia and hyperalgesia. Eur J Pain. 2014 Mar;18(3):315-25. doi: 10.1002/j.1532-2149.2013.00380.x. Epub 2013 Aug 20.
citation: Leslie TA, Greaves MW, Yosipovitch G. Current topical and systemic therapies for itch. Handb Exp Pharmacol. 2015;226:337-56. doi: 10.1007/978-3-662-44605-8_18.
citation: Heyneman CA. Topical nonsteroidal antiinflammatory drugs for acute soft tissue injuries. Ann Pharmacother. 1995 Jul-Aug;29(7-8):780-2. doi: 10.1177/106002809502907-822.
citation: Andersen HH, Gazerani P, Arendt-Nielsen L. High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde. J Pain. 2016 Aug;17(8):919-29. doi: 10.1016/j.jpain.2016.05.004. Epub 2016 May 31.