L-menthol as a Topical Counter-irritant to TRPA1-induced Neurogenic Inflammation and Pain

NCT02653703 | Completed

• 1 other identifier: N-20130005
• Study Type: interventional
• Target: 14
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Inflammation; Pruritus; Hyperalgesia

Outcome Measures

Primary Outcomes (1)

• Spontaneous pain intensity [self-reported on a visual analog scale]

  Rating of the overall pain intensity on a visual analog scale (VAS ranging from "No pain" = 0, to "worst imaginable pain" =10) once every minute

  0-20 minutes with a sampling frequency of 1/1 min

Secondary Outcomes (3)

• Neurogenic inflammation [Measured by Laser speckle flowmetry in a 3x3 cm area]

  20-25 minutes post induction

• Heat hyperalgesia

  25-27.5 minutes post induction

• Mechanical hyperalgesia

  27.5-30 minutes post induction

Study Arms (2)

Vehicle, topical ethanol 96%

PLACEBO COMPARATOR

Exposure: 10 % topical trans-cinnamaldehyde \[CAS Number: 14371-10-9\] Vehicle: 96% ethanol

Other: Vehicle, topical ethanol 96%

Topical L-menthol 40%

EXPERIMENTAL

Exposure: 10 % trans-cinnamaldehyde \[CAS Number: 14371-10-9\] Intervention: 40% l-menthol \[CAS Number: 2216-51-5\] Vehicle: 96% ethanol

Other: Topical L-menthol 40%

Interventions

Topical L-menthol 40% OTHER

Naturally occurring local anaesthetic, counterirritant and TPRM8-agonist. CAS Number: 2216-51-5

Also known as: Menthol

Topical L-menthol 40%

Vehicle, topical ethanol 96% OTHER

Organic solvent CAS Number: 64-17-5

Vehicle, topical ethanol 96%

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aalborg University: lead

Related Publications (8)

• 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.

  PMID: 24664788 BACKGROUND

• 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.

  PMID: 25792226 BACKGROUND

• 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.

  PMID: 15931068 BACKGROUND

• 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.

  PMID: 18440147 BACKGROUND

• 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.

  PMID: 23963768 BACKGROUND

• 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.

  PMID: 25861788 BACKGROUND

• 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.

  PMID: 8520097 BACKGROUND

• 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.

  PMID: 27260636 DERIVED

MeSH Terms

Conditions

Inflammation; Pruritus; Hyperalgesia

Interventions

Menthol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Cyclohexane Monoterpenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Monoterpenes; Terpenes; Lipids

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, PharmD, Ph.D.

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 12, 2016
• Study Start: October 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 12, 2016

Record last verified: 2016-01