Dose-response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation

Pain. 2017 Sep;158(9):1723-1732. doi: 10.1097/j.pain.0000000000000979.

Abstract

Despite being a ubiquitous animal pain model, the natural TRPA1-agonist allyl isothiocyanate (AITC, also known as "mustard oil") has only been sparsely investigated as a potential human surrogate model of pain, sensitization, and neurogenic inflammation. Its dose-response as an algogenic, sensitizing irritant remains to be elucidated in human skin. Three concentrations of AITC (10%, 50%, and 90%) and vehicle (paraffin) were applied for 5 minutes to 3 × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain intensity (visual analog scale 0-100 mm) and pain quality were assessed. In addition, a comprehensive battery of quantitative sensory tests was conducted, including assessment of mechanical and thermal sensitivity. Neurogenic inflammation was quantified using full-field laser perfusion imaging. Erythema and hyperpigmentation were assessed before, immediately after, and ≈64 hours after AITC exposure. AITC induced significant dose-dependent, moderate-to-severe spontaneous burning pain, mechanical and heat hyperalgesia, and dynamic mechanical allodynia (P < 0.05). No significant differences in induced pain hypersensitivity were observed between the 50% and 90% AITC concentrations. Acute and prolonged inflammation was evoked by all concentrations, and assessments by full-field laser perfusion imaging demonstrated a significant dose-dependent increase with a ceiling effect from 50% to 90%. Topical AITC application produces pain and somatosensory sensitization in a dose-dependent manner with optimal concentrations recommended to be >10% and ≤50%. The model is translatable to humans and could be useful in pharmacological proof-of-concept studies of TRPA1-antagonists, analgesics, and anti-inflammatory compounds or for exploratory clinical purposes, eg, loss- or gain-of-function in peripheral neuropathies.

MeSH terms

  • Administration, Topical
  • Adult
  • Dose-Response Relationship, Drug
  • Female
  • Functional Laterality
  • Healthy Volunteers
  • Humans
  • Hyperalgesia / chemically induced*
  • Isothiocyanates / administration & dosage
  • Isothiocyanates / pharmacology*
  • Male
  • Models, Theoretical
  • Neurogenic Inflammation / chemically induced*
  • Pain / chemically induced*
  • Pain / physiopathology
  • Pain Measurement
  • Pain Threshold / drug effects*
  • Physical Stimulation
  • Pigmentation / drug effects
  • Random Allocation
  • TRPA1 Cation Channel / antagonists & inhibitors*
  • Young Adult

Substances

  • Isothiocyanates
  • TRPA1 Cation Channel
  • allyl isothiocyanate