Department of Anesthesiology and Operative Intensive Care, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
Rehaklinik Bellikon, Bellikon, Switzerland.
Pain. 2018 Mar;159(3):416-426. doi: 10.1097/j.pain.0000000000001108.
Nerve growth factor (NGF) injected into the human skin causes local hyperalgesia to mechanical and electrical stimuli lasting for weeks. Pig data suggested axonal sensitization of C-nociceptors as a contributing mechanism. Here, we recorded single C-nociceptors in 11 human subjects 3 weeks after intracutaneous injection of 1 μg NGF into the foot dorsum. For each identified unit, the receptive field was mapped and, whenever possible, we recorded 2 terminal branches of the same unit, 1 from the hyperalgesic NGF-site ("inside") and the other from the nonsensitized skin ("outside"). In the saline-treated control feet, mechano-insensitive nociceptors (CMi) were more abundant than at the NGF sites (36% vs 19%). Units with axonal properties of CMi fibres but displaying positive mechanical responses ("CMi-like") dominated at the NGF site (27% vs 6%). Moreover, axonal branches innervating the hyperalgesic skin displayed significantly lower electrical thresholds and less activity-dependent conduction velocity slowing when compared with "outside" or control skin. The "inside" branches also showed long-lasting after-discharges and less adaptation to repeated mechanical stimuli. NGF-induced long-term nociceptor hyperexcitability was maximum at the terminal branches directly treated with NGF. The sensitization included sensory and axonal components affecting both activation thresholds and supra-threshold responses. Our data suggest that a combination of sensory sensitization and axonal hyperexcitability is underlying the localized hyperalgesia by facilitating action potential generation and conduction. Axonal changes were also found in the asymptomatic skin surrounding the NGF-treatment sites, thereby possibly reflecting "nociceptive priming."
神经生长因子（NGF）注入人体皮肤会导致机械和电刺激的局部痛觉过敏，持续数周。猪的数据表明 C 伤害感受器的轴突敏化是一种促成机制。在这里，我们在 11 名人类受试者的足部背侧皮内注射 1μg NGF 3 周后，记录了单个 C 伤害感受器。对于每个鉴定出的单位，记录了其感受野，并在可能的情况下，记录了同一单位的 2 个末端分支，1 个来自痛觉过敏的 NGF 部位（“内部”），另 1 个来自未致敏的皮肤（“外部”）。在生理盐水处理的对照足部，机械不敏感的伤害感受器（CMi）比 NGF 部位更丰富（36%比 19%）。具有 CMi 纤维轴突特性但显示阳性机械反应的单位（“CMi 样”）在 NGF 部位占主导地位（27%比 6%）。此外，支配痛觉过敏皮肤的轴突分支的电阈值明显降低，活动依赖性传导速度减慢也明显低于“外部”或对照皮肤。与“外部”或对照皮肤相比，“内部”分支还表现出持久的后放电和对重复机械刺激的适应性降低。NGF 诱导的长期伤害感受器兴奋性增加在直接接受 NGF 处理的末端分支中最大。这种敏化包括感觉和轴突成分，影响激活阈值和阈上反应。我们的数据表明，感觉敏化和轴突过度兴奋的结合通过促进动作电位的产生和传导，是导致局部痛觉过敏的原因。在 NGF 治疗部位周围无症状的皮肤中也发现了轴突变化，因此可能反映了“伤害感受性启动”。
