Nerve growth factor induces sensitization of nociceptors without evidence for increased intraepidermal nerve fiber density
Nerve growth factor induces sensitization of nociceptors without evidence for increased intraepidermal nerve fiber density
复制标题
DOI：
10.1016/j.pain.2013.07.036
复制
发表时间：
2013-11-01
期刊：
影响因子：
7.4
通讯作者：
Obreja, Otilia
中科院分区：
文献类型：
--
作者：
Hirth, Michael;Rukwied, Roman;Obreja, Otilia
神经生长因子（NGF）参与与慢性疼痛相关的伤害性处理的长期敏化。功能和结构（“萌芽”）变化可能会有所贡献。因此，人类报告皮内注射NGF后对机械和电刺激的持久痛觉过敏，并且已经报告NGF诱导的发芽是癌症骨痛和内脏痛的基础。使用类人动物模型，我们研究了皮内神经生长因子治疗后3周无髓鞘猪伤害感受器的结构和功能之间的关系。轴突和感觉特性进行了研究，在体内单纤维电生理学和免疫组织化学。根据机械反应和传导速度的活动依赖性减慢（ADS）对细胞外记录的C纤维进行分类。表皮内神经纤维（IENF）的密度进行了评估，在猪和人类志愿者使用相同的NGF模型免疫组织化学。神经生长因子增加传导速度，减少ADS和传播失败的机械不敏感的伤害感受器。在神经生长因子治疗的皮肤区域内的机械敏感性C伤害感受器的比例从45.1%（对照）增加到71%，并且它们的中值机械阈值从40 mN降低到20 mN。应用NGF后，伤害感受器的机械感受野从25 mm增加到43 mm（2）。然而，在结构水平上，神经生长因子没有增加IENF密度。总之，皮内神经生长因子诱导持久的轴突和机械致敏猪C伤害感受器，对应于在人类中观察到的痛觉过敏。致敏并不伴随着IENF密度的增加，这表明NGF诱导的痛觉过敏可能不依赖于神经纤维密度的变化，但可能与以前沉默的伤害感受器的募集有关。(C)2013年国际疼痛研究协会。Elsevier B.V.出版，保留所有权利。
Nerve growth factor (NGF) is involved in the long-term sensitization of nociceptive processing linked to chronic pain. Functional and structural ("sprouting") changes can contribute. Thus, humans report long-lasting hyperalgesia to mechanical and electrical stimulation after intradermal NGF injection and NGF-induced sprouting has been reported to underlie cancer bone pain and visceral pain. Using a human-like animal model we investigated the relationship between the structure and function of unmyelinated porcine nociceptors 3 weeks after intradermal NGF treatment. Axonal and sensory characteristics were studied by in vivo single-fiber electrophysiology and immunohistochemistry. C fibers recorded extracellularly were classified based on mechanical response and activity-dependent slowing (ADS) of conduction velocity. Intraepidermal nerve fiber (IENF) densities were assessed by immunohistochemistry in pigs and in human volunteers using the same NGF model. NGF increased conduction velocity and reduced ADS and propagation failure in mechano-insensitive nociceptors. The proportion of mechano-sensitive C nociceptors within NGF-treated skin areas increased from 45.1% (control) to 71% and their median mechanical thresholds decreased from 40 to 20 mN. After NGF application, the mechanical receptive fields of nociceptors increased from 25 to 43 mm(2). At the structural level, however, IENF density was not increased by NGF. In conclusion, intradermal NGF induces long-lasting axonal and mechanical sensitization in porcine C nociceptors that corresponds to hyperalgesia observed in humans. Sensitization is not accompanied by increased IENF density, suggesting that NGF-induced hyperalgesia might not depend on changes in nerve fiber density but could be linked to the recruitment of previously silent nociceptors. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.