Laboratory for Experimental Cutaneous Pain and Itch Research, SMI®, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
The Allergy Clinic, Department of Dermato-Allergology, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark.
Exp Dermatol. 2018 Mar;27(3):258-267. doi: 10.1111/exd.13508.
Exaggerated itch responses to pruritic chemical provocations and mechanical stimuli are evident in patients with chronic itch, for example, 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 (2 cm diameter) were UVB irradiated with ≤2 × minimal erythemal dose, and two non-irradiated areas were used as controls. Sixteen healthy volunteers participated in the NGF experiment and had 2 μg intradermally injected (4 × 50 μL in 2 cm 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 < .01) and hyperknesis (P < .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 < .05). This suggests that these models are of limited value as proxies for itch sensitization to pruritogens observed, e.g., in inflammatory dermatoses.
在慢性瘙痒患者中，例如特应性皮炎患者，对瘙痒性化学刺激物和机械刺激的过度瘙痒反应是明显的。目前使用的瘙痒人类模型并不能说明这种瘙痒致敏的特征，而且临床瘙痒致敏的机制尚不清楚。本研究利用两种已建立的皮肤伤害感受性致敏人类模型来探讨预先存在的炎症性痛觉过敏（紫外线 B 辐射；“UVB”）和非炎症性神经营养性疼痛致敏（神经生长因子；“NGF”）如何改变对化学和机械诱发瘙痒的敏感性。二十名健康志愿者参加了 UVB 实验。将 2 个前臂掌侧（直径 2 厘米）用 ≤2×最小红斑剂量的 UVB 辐射，并用 2 个非辐射区域作为对照。16 名健康志愿者参加了 NGF 实验，将 2μg 经皮注入（4×50μL 在 2cm 直径区域）到双侧前臂掌侧。生理盐水作为对照。进行了疼痛敏感性测量（机械和热痛阈值）以验证模型。随后，在致敏皮肤区域使用组胺和毛毡藜刺状突起诱发瘙痒，并使用视觉模拟量表评估瘙痒/疼痛。在每次瘙痒刺激之前/之后，使用 von Frey 纤维探测机械性超敏反应（对点状刺激的瘙痒增加）。UVB 和 NGF 模型均引起强烈的原发性机械性痛觉过敏（P<.01）和超敏反应（P<.05）。两种模型均未增加对化学性瘙痒刺激的瘙痒反应，但对组胺和毛毡藜刺状突起的疼痛评分均显著增加（P<.05）。这表明这些模型作为观察到的炎性皮肤病等致痒原的瘙痒致敏的替代物的价值有限。
