Acute effects of NGF on capsaicin currents in nociceptive neurons

虽然现在已经很好地接受了NGF在炎性疼痛中的作用，但是这种神经营养因子使外周中的伤害感受神经元敏感的机制仍然没有很好地理解。在某种程度上，这个问题是由皮肤中表达神经生长因子高亲和力受体trkA的神经和非神经细胞类型的多样性引起的。NGF通过表达trkA的肥大细胞间接影响伤害感受器的可能性也获得了一些实验支持。然而，有一些证据表明，神经生长因子可以绕过肥大细胞，使伤害感受器对有害的热敏感。我们最近的初步数据使用神经生长因子急性条件下，辣椒素诱发电流在分离的DRG神经元表明，神经生长因子可能会引起直接影响DRG神经元表明，神经生长因子可能会引起直接影响DRG神经元。辣椒素可以被视为有害热的替代品，因为后者激活辣椒素受体VR 1。因此，NGF可能直接敏感热毒反应。本文拟用膜片钳技术进一步研究这一作用，以验证以下假说：a）神经营养因子通过其相应的trk受体直接影响伤害性神经元对伤害性刺激的反应：B）NGF对DRG小细胞胞体和多模态伤害性感受器终末的辣椒素和伤害性热反应具有相同的增敏作用; c）供应发炎皮肤或具有遗传改变的神经营养因子表达水平的皮肤的细胞对急性应用的神经营养因子的反应不同。这些实验的完成将提供进一步了解的生理学和神经生长因子的伤害感受器对有害热的敏化的生理学。

Although a role for NGF in inflammatory pain is now well accepted, the mechanism by which this neurotrophin sensitizes nociceptive neurons in the periphery is still not well understood. In part this problem arises from the multiplicity of cell types, both neural and non-neural, in the skin that expresses trkA, the high affinity receptor for NGF. The possibility that NGF affects nociceptors indirectly via trkA-expressing mast cells also obtained some experimental support. However, there is some evidence that NGF can bypass mast cells to sensitize nociceptors to noxious heat. Our recent preliminary data using NGF to acutely condition, capsaicin evoked currents in isolated DRG neurons indicate that NGF may elicit direct effects on DRG neurons indicate that NGF may elicit direct effects on DRG neurons. Capsaicin can be viewed as a surrogate for noxious heat since the latter activates the capsaicin receptor VR1. It therefore follows that NGF may sensitive the response to noxious heat directly. Further study of this action is proposed using patch clamp methodology to examine a number of hypotheses: a) Neurotrophins have a direct effect on the response of nociceptive neurons to nociceptive stimuli via the action of their corresponding trk receptor; b) NGF has the same sensitizing action on the capsaicin and noxious heat responses of both the somata of small DRG cells and the terminals of polymodal nociceptors; c) Cells supplying inflamed skin or skin with genetically altered levels of neurotrophin expression respond differently to acutely applied neurotrophins. Completion of these experiments will provide further understanding of the physiology and physiology of the sensitization of nociceptors to noxious heat by NGF.