期刊
JOURNAL OF NEUROSCIENCE
卷 26, 期 1, 页码 126-137出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3686-05.2006
关键词
neurotrophin; TrkB; neuronal plasticity; periaqueductal gray; medulla; pain
资金
- NIDA NIH HHS [DA10275, R01 DA010275] Funding Source: Medline
- NIDCR NIH HHS [DE11964, R01 DE011964] Funding Source: Medline
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.
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