Andersen H H, Elberling J, Sharma N, Hauberg L E, Gazerani P, Arendt-Nielsen L
Laboratory for Experimental Cutaneous Pain Research, SMI®, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark.
Department of Dermato-Allergology, Copenhagen University Hospital, Herlev-Gentofte Hospital, Copenhagen, Denmark.
Eur J Pain. 2017 Jul;21(6):1098-1109. doi: 10.1002/ejp.1013. Epub 2017 Feb 17.
Chronic pain patients with sensitization may exhibit decreased sensitivity to normally pruritogenic sensory stimuli and moreover occasionally perceive these as painful. This study explored the relationship between itch and pain, by evaluating histaminergic and non-histaminergic itch evoked in capsaicin-induced allodynic and hyperalgesic areas.
In 28 healthy volunteers, capsaicin (100 μg/0.1 mL) was injected intradermally in the volar forearm to establish secondary dysesthesias. After the capsaicin-induced pain subsided, the areas of allodynia and hyperalgesia were mapped and itch was provoked inside these areas by histamine (10 mg/mL) and cowhage (25-40 spicules). The evoked itch and pain were recorded on a visual analogue scale (VAS 0-10 cm). Contralateral injection of 0.1 mL isotonic saline served as a control.
Histaminergic and non-histaminergic evoked itch were significantly decreased when provoked in allodynic skin (p < 0.05). The area-under-the-curve of the evoked itch was reduced -43% from 18.0 ± 2.6 cm in normal skin to 10.3 ± 1.8 cm in allodynic skin (p < 0.01) for cowhage and -56% from 20.0 ± 3.5 cm in normal skin to 8.8 ± 2.3 cm allodynic skin (p < 0.001) for histamine. The pain responses to the pruritogens were not significantly altered between the areas of allodynia and normal skin (p > 0.1). An additional experiment showed that pinprick hyperalgesia in the absence of allodynia was sufficient to evoke the observed reduced sensitivity to itch stimuli.
Cutaneous sensitization (secondary allodynia and hyperalgesia) reduced itch responses regardless of the type of itch model applied and without attenuation of the associated pruritogen-induced pain responses. This could explain the decreased sensitivity to itch provocations previously observed in patients with chronic pain.
This study shows that the neuronal sensitization processes underlying the development secondary hyperalgesia involve significant gating of histaminergic as well as non-histaminergic pruriceptive transmission. Because these itch provocations normally target specific subpopulations of C-nociceptors they could be of relevance for exploratory purposes in pain patients.
伴有感觉过敏的慢性疼痛患者可能对通常会引起瘙痒的感觉刺激表现出敏感性降低，而且偶尔会将这些刺激感知为疼痛。本研究通过评估辣椒素诱导的异常性疼痛和痛觉过敏区域中组胺能和非组胺能引起的瘙痒，探讨瘙痒与疼痛之间的关系。
在28名健康志愿者的掌侧前臂皮内注射辣椒素（100μg/0.1mL）以建立继发性感觉异常。辣椒素诱导的疼痛消退后，绘制异常性疼痛和痛觉过敏区域，并通过组胺（10mg/mL）和刺荨麻（25 - 40根刺）在这些区域诱发瘙痒。诱发的瘙痒和疼痛通过视觉模拟量表（VAS 0 - 10cm）记录。对侧注射0.1mL等渗盐水作为对照。
在异常性疼痛皮肤中诱发时，组胺能和非组胺能诱发的瘙痒显著降低（p < 0.05）。诱发瘙痒的曲线下面积，刺荨麻诱发的从正常皮肤的18.0±2.6cm降至异常性疼痛皮肤的10.3±1.8cm，降低了43%（p < 0.01）；组胺诱发的从正常皮肤的20.0±3.5cm降至异常性疼痛皮肤的8.8±2.3cm，降低了56%（p < 0.001）。在异常性疼痛区域和正常皮肤之间，对致痒原的疼痛反应没有显著改变（p > 0.1）。另一项实验表明，在没有异常性疼痛的情况下，针刺样痛觉过敏足以引起观察到的对瘙痒刺激的敏感性降低。
皮肤致敏（继发性异常性疼痛和痛觉过敏）会降低瘙痒反应，无论应用何种瘙痒模型，且不会减弱相关致痒原诱导的疼痛反应。这可以解释先前在慢性疼痛患者中观察到的对瘙痒刺激的敏感性降低。
本研究表明，继发性痛觉过敏发生过程中的神经元致敏过程涉及对组胺能以及非组胺能瘙痒感受性传递的显著调节。由于这些瘙痒刺激通常针对特定的C类伤害感受器亚群，它们可能对疼痛患者的探索性研究具有相关性。
