UVB and NGF-induced cutaneous sensitization in humans selectively augment cowhage and histamine-induced pain and mechanical hyperknesis

Abstract

Exaggerated itch responses to pruritic chemical provocations and mechanical stimuli are evident in patients with chronic itch, e.g., in atopic dermatitis. Currently used human models of itch do not account for such itch sensitization features and the mechanisms underlying clinical itch sensitization are unknown. This study utilized two established human models of cutaneous nociceptive sensitization to explore how pre-established inflammatory hyperalgesia (ultraviolet-B-irradiation; 'UVB') and non-inflammatory neurotrophic pain sensitization (nerve growth factor; 'NGF') alter sensitivity to chemical and mechanically-evoked itch. Twenty healthy volunteers participated in the UVB-experiment. Six volar forearm areas (2cm diameter) were UVB-irradiated with ≥2 x minimal erythemal dose and two non-irradiated areas were used as controls. Sixteen healthy volunteers participated in the NGF-experiment and had 2μg intradermally injected (4x50μL in 2cm diameter areas) into both volar forearms. Isotonic saline was applied as control. Pain sensitivity measurements (mechanical and heat pain thresholds) were conducted to validate the models. Subsequently, itch was evoked using histamine and cowhage spicules in the sensitized skin areas and itch/pain was rated using visual analogue scales. Mechanical hyperknesis (increased itch to punctuate stimuli) was probed with von Frey filaments before/after each itch provocation. Both UVB- and NGF-models induced robust primary mechanical hyperalgesia (p<0.01) and hyperknesis (p<0.05). Neither of the models augmented itch in response to chemical itch provocations but significant increases specifically for pain ratings were observed for both histamine and cowhage (p<0.05). This suggests that these models are of limited value as proxies for the itch sensitization to pruritogens observed in inflammatory dermatoses.

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