Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in spinal dorsal horn
Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in spinal dorsal horn
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DOI：
10.1006/mcne.2002.1205
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发表时间：
2002-12-01
影响因子：
3.5
通讯作者：
McMahon, SB
中科院分区：
文献类型：
--
作者：
Pezet, S;Malcangio, M;McMahon, SB
一些证据表明，脑源性神经营养因子(BDNF)是中枢性痛觉神经调节剂。我们检测了不同类型的外周刺激激活脊髓中BDNF高亲和力受体TrkB的能力。我们发现，有害的化学、机械或热刺激，而不是无害的刺激，会导致脊髓中Trk的磷酸化。这些变化是迅速和短暂的，仅限于适合身体定位的脊柱节段。我们在体外和体内观察到，外源性BDNF诱导ERK迅速激活，ERK是一种在急性疼痛发生中重要的信号转导通路。最后，我们发现在体内用TrkB-Ig G融合分子隔离BDNF可以显著降低伤害性刺激引起的ERK的激活。这些数据表明，BDNF一旦从初级传入伤害性感受器释放出来，就通过刺激突触后TrkB受体和随后激活ERK而在痛处理中发挥神经调制作用。
Several lines of evidence suggest that the brain-derived neurotrophic factor (BDNF) acts as central pain neuromodulator. We examined the ability of different types of peripheral stimulation to activate the BDNF high-affinity receptor, TrkB, in the spinal cord. We found that noxious chemical, mechanical, or thermal stimuli, but not innocuous stimuli, caused Trk phosphorylation in the spinal cord. These changes were rapid and transient and restricted to somatotopically appropriate spinal segments. We observed, both in vitro and in vivo, that exogenous BDNF induced a rapid activation of ERK, a signaling kinase important in the development of acute pain. Finally, we found that sequestering BDNF in vivo with a TrkB-IgG fusion molecule significantly reduced the activation of ERK evoked by noxious stimulation. These data suggest that BDNF, once released with activity from primary afferent nociceptors, exerts a neuromodulatory role in pain processing through stimulation of postsynaptic TrkB receptors and subsequent activation of ERK.