NGF-mediated sensitization of the excitability of rat sensory neurons is prevented by a blocking antibody to the p75 neurotrophin receptor

被引:65
作者
Zhang, YH [1 ]
Nicol, GD [1 ]
机构
[1] Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA
关键词
nerve growth factor; p75 neurotrophin receptor; ceramide; excitability; sensitization;
D O I
10.1016/j.neulet.2004.05.042
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Nerve growth factor (NGF) can play a causal role in the initiation of hyperalgesia. Recent work demonstrates that NGF can act directly on nociceptive sensory neurons to augment their sensitivity to a variety of stimuli. Based on the existing literature, it is not clear whether this sensitization is mediated by the high-affinity TrkA receptor or the low-affinity p75 neurotrophin receptor. We examined whether a blocking antibody to the p75 neurotrophin receptor can prevent the NGF-induced enhancement of excitability in capsaicin-sensitive small-diameter sensory neurons that have been isolated from the adult rat. In this report, pretreatment with the p75 blocking antibody completely prevents the NGF-induced increase in the number of action potentials evoked by a ramp of depolarizing current as well as the suppression of a delayed rectifier-type of potassium current(s) in these neurons. Although the sensitization by NGF was blocked, the antibody had no effect on the capacity of ceramide, a putative downstream signaling molecule, to either enhance the excitability or inhibit the potassium current. These results indicate that NGF can increase the excitability of nociceptive sensory neurons through activation of the p75 neurotrophin receptor and its consequent liberation of ceramide from neuronal sphingomyelins. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:187 / 192
页数:6
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