Acute effects of NGF on capsaicin currents in nociceptive neurons

尽管神经营养因子在炎症性疼痛中的作用已被广泛接受，但这种神经营养因子使外周伤害性神经元致敏的机制仍未得到很好的理解。在某种程度上，这个问题源于皮肤中表达NGF高亲和力受体trkA的细胞类型的多样性，包括神经细胞和非神经细胞。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得到了一些实验支持。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热量敏感。我们最近使用NGF对分离DRG神经元急性条件下辣椒素诱发电流的初步数据表明，NGF可能对DRG神经元产生直接作用，表明NGF可能对DRG神经元产生直接作用。辣椒素可以被视为毒辣的替代品，因为后者激活辣椒素受体VR1。因此，NGF可能直接敏感对有害热的反应。我们建议使用膜片钳方法进一步研究这一作用，以检验一些假设：a)神经营养物质通过其相应的trk受体的作用直接影响伤害性神经元对伤害性刺激的反应；b) NGF对小DRG细胞体和多模伤害感受器末端的辣椒素和有害热反应具有相同的增敏作用；c)供应炎症皮肤或神经营养因子基因表达水平改变的皮肤的细胞对急性应用神经营养因子的反应不同。这些实验的完成将进一步了解NGF对伤害感受器致敏的生理学和生理学。

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.