Weinkauf B, Dusch M, van der Ham J, Benrath J, Ringkamp M, Schmelz M, Rukwied R
Department of Orthopedics and Traumatology, University Medical Center Mannheim, Germany.
Department of Anaesthesiology, Mannheim, Heidelberg University, Germany.
Eur J Pain. 2016 Feb;20(2):215-22. doi: 10.1002/ejp.710. Epub 2015 Apr 2.
Mechano-sensitive and mechano-insensitive C-nociceptors in human skin differ in receptive field sizes and electrical excitation thresholds, but their distinct functional roles are yet unclear.
After blocking the lateral femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin(®) 1%), we mapped the skin innervation territory being anaesthetic to mechanical pin prick but sensitive to painful transcutaneous electrical stimuli. Such 'differentially anaesthetic zones' indicated that the functional innervation with mechano-sensitive nociceptors was absent but the innervation with mechano-insensitive nociceptors remained intact. In these areas, we explored heat pain thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon reflex flare.
In differentially anaesthetic skin, heat pain thresholds were above the cut-off of 50°C (non-anaesthetized skin 47 ± 0.4°C). Pain ratings to 30 μL pH 4 injections were reduced compared to non-anaesthetized skin (48 ± 9 vs. 79 ± 6 VAS; p < 0.01). The axon reflex flare area did not differ between these zones (7.8 ± 1.4 cm(2) vs. 8.3 ± 0.5 cm(2) ). Histamine iontophoresis still caused pruritus in differentially anaesthetized skin in five of eight subjects (VAS 26 ± 14), whereas itch upon cowhage spicules was absent (VAS 0 vs. 29 ± 11 in non-anaesthetized skin).
We conclude that activation of mechano-insensitive nociceptors is sufficient to provoke itch by histamine- and acid-induced pain. The mechano-sensitive nociceptors are crucial for cowhage-induced itch and for the assessment of heat pain thresholds.
人类皮肤中的机械敏感型和机械不敏感型C类伤害感受器在感受野大小和电刺激阈值方面存在差异，但其独特的功能作用尚不清楚。
在八名健康男性受试者（3毫升1%罗哌卡因）中阻断股外侧皮神经后，我们绘制了对机械针刺麻醉但对经皮电刺激疼痛敏感的皮肤神经支配区域。这种“差异麻醉区”表明机械敏感型伤害感受器的功能性神经支配缺失，但机械不敏感型伤害感受器的神经支配保持完整。在这些区域，我们探究了热痛阈值、低pH值诱导的疼痛、刺荨麻和组胺诱导的瘙痒以及轴突反射性潮红。
在差异麻醉的皮肤中，热痛阈值高于50°C的临界值（未麻醉皮肤为47±0.4°C）。与未麻醉皮肤相比，对30微升pH值为4的注射的疼痛评分降低（48±9与79±6视觉模拟评分；p<0.01）。这些区域之间的轴突反射性潮红面积没有差异（7.8±1.4平方厘米与8.3±0.5平方厘米）。在八名受试者中的五名中，组胺离子电渗疗法在差异麻醉的皮肤中仍会引起瘙痒（视觉模拟评分为26±14），而刺荨麻针引起的瘙痒则不存在（视觉模拟评分为0，未麻醉皮肤为29±11）。
我们得出结论，机械不敏感型伤害感受器的激活足以通过组胺和酸诱导的疼痛引发瘙痒。机械敏感型伤害感受器对于刺荨麻诱导的瘙痒和热痛阈值的评估至关重要。
