Supraspinal brain-derived neurotrophic factor signaling: A novel mechanism for descending pain facilitations
Supraspinal brain-derived neurotrophic factor signaling: A novel mechanism for descending pain facilitations
复制标题
DOI：
10.1523/jneurosci.3686-05.2006
复制
发表时间：
2006-01-04
影响因子：
5.3
通讯作者：
Ren, K
中科院分区：
文献类型：
--
作者：
Guo, W;Robbins, MT;Ren, K
在成年哺乳动物脑中，脑源性神经营养因子（BDNF）与突触的长期可塑性密切相关。在这里，我们表明，脊髓上BDNF-酪氨酸激酶受体B（Trk B）信号有助于疼痛易化。我们发现，含有BDNF的神经元在中脑导水管周围灰质（PAG），疼痛调制的中央结构，项目和释放BDNF在延髓头端腹内侧（RVM），PAG和脊髓之间的中继。PAG中的BDNF和RVM神经元中的TrkB磷酸化在炎症后上调。RVM内隔离BDNF和通过RNA干扰敲低TrkB减轻炎性疼痛。向RVM中微量注射BDNF（10-100 fmol）促进伤害感受，这依赖于NMDA受体（NMDAR）。RVM切片的体外研究表明，BDNF通过涉及IP 3、PKC和Src的信号转导级联反应诱导RVM中NMDAR NR 2A亚基的酪氨酸磷酸化。脊髓上BDNF-TrkB信号传导代表了持续性疼痛发展的一种先前未知的机制。我们的研究结果还警告说，应用BDNF从CNS疾病中恢复可能会导致不希望的中枢性疼痛。
In the adult mammalian brain, brain-derived neurotrophic factor ( BDNF) is critically involved in long-term synaptic plasticity. Here, we show that supraspinal BDNF-tyrosine kinase receptor B (TrkB) signaling contributes to pain facilitation. We show that BDNF-containing neurons in the periaqueductal gray (PAG), the central structure for pain modulation, project to and release BDNF in the rostral ventromedial medulla (RVM), a relay between the PAG and spinal cord. BDNF in PAG and TrkB phosphorylation in RVM neurons are upregulated after inflammation. Intra-RVM sequestration of BDNF and knockdown of TrkB by RNA interference attenuate inflammatory pain. Microinjection of BDNF (10-100 fmol) into the RVM facilitates nociception, which is dependent on NMDA receptors (NMDARs). In vitro studies with RVM slices show that BDNF induces tyrosine phosphorylation of the NMDAR NR2A subunit in RVM via a signal transduction cascade involving IP3, PKC, and Src. The supraspinal BDNF-TrkB signaling represents a previously unknown mechanism underlying the development of persistent pain. Our findings also caution that application of BDNF for recovery from CNS disorders could lead to undesirable central pain.