PMID- 32149862
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210514
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Linking)
VI  - 161
IP  - 7
DP  - 2020 Jul
TI  - Activation of EphB receptors contributes to primary sensory neuron excitability 
      by facilitating Ca2+ influx directly or through Src kinase-mediated 
      N-methyl-D-aspartate receptor phosphorylation.
PG  - 1584-1596
LID - 10.1097/j.pain.0000000000001855 [doi]
AB  - EphrinB-EphB receptor tyrosine kinases have been demonstrated to play important 
      roles in pain processing after peripheral nerve injury. We have previously 
      reported that ephrinB-EphB receptor signaling can regulate excitability and 
      plasticity of neurons in spinal dorsal horn, and thus contribute to spinal 
      central sensitization in neuropathic pain. How EphB receptor activation 
      influences excitability of primary neurons in dorsal root ganglion (DRG), 
      however, remains unknown. Here, we report that EphB receptor activation 
      facilitates calcium influx through N-methyl-D-aspartate receptor (NMDAR) 
      dependent and independent manners. In cultured DRG cells from adult rats, EphB1 
      and EphB2 receptors were expressed in neurons, but not the glial cells. Bath 
      application of EphB receptor agonist ephrinB2-Fc induced NMDAR-independent Ca 
      influx, which was from the extracellular space rather than endoplasmic reticulum. 
      EphB receptor activation also greatly enhanced NMDAR-dependent Ca influx and NR2B 
      phosphorylation, which was prevented by pretreatment of Src kinase inhibitor PP2. 
      In nerve-injured DRG neurons, elevated expression and activation of EphB1 and 
      EphB2 receptors contributed to the increased intracellular Ca concentration and 
      NMDA-induced Ca influx. Repetitive intrathecal administration of EphB2-Fc 
      inhibited the increased phosphorylation of NR2B and Ca-dependent subsequent 
      signals Src, ERK, and CaMKII as well as behaviorally expressed pain after nerve 
      injury. These findings demonstrate that activation of EphB receptors can modulate 
      DRG neuron excitability by facilitating Ca influx directly or through Src kinase 
      activation-mediated NMDA receptor phosphorylation and that EphB receptor 
      activation is critical to DRG neuron hyperexcitability, which has been considered 
      critical to the subsequent spinal central sensitization and neuropathic pain.
FAU - Ma, Pingchuan
AU  - Ma P
AD  - SUSTech Center for Pain Medicine, School of Medicine, Southern University of 
      Science and Technology, Shenzhen, Guangdong, China.
AD  - Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, 
      United States.
FAU - Chen, Peng
AU  - Chen P
AD  - SUSTech Center for Pain Medicine, School of Medicine, Southern University of 
      Science and Technology, Shenzhen, Guangdong, China.
FAU - Zhou, Zhao-Lin
AU  - Zhou ZL
AD  - SUSTech Center for Pain Medicine, School of Medicine, Southern University of 
      Science and Technology, Shenzhen, Guangdong, China.
FAU - Mo, Ru-Fan
AU  - Mo RF
AD  - SUSTech Center for Pain Medicine, School of Medicine, Southern University of 
      Science and Technology, Shenzhen, Guangdong, China.
FAU - Wu, Mingzheng
AU  - Wu M
AD  - SUSTech Center for Pain Medicine, School of Medicine, Southern University of 
      Science and Technology, Shenzhen, Guangdong, China.
AD  - Department of Neurobiology, Northwestern University, Evanston, IL, United States.
FAU - Song, Xue-Jun
AU  - Song XJ
AD  - SUSTech Center for Pain Medicine, School of Medicine, Southern University of 
      Science and Technology, Shenzhen, Guangdong, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.10.1 (Receptors, Eph Family)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium
MH  - Hyperalgesia
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Receptors, Eph Family/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Sensory Receptor Cells/metabolism
MH  - *src-Family Kinases/metabolism
EDAT- 2020/03/10 06:00
MHDA- 2021/05/15 06:00
CRDT- 2020/03/10 06:00
PHST- 2020/03/10 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/03/10 06:00 [entrez]
AID - 00006396-202007000-00016 [pii]
AID - 10.1097/j.pain.0000000000001855 [doi]
PST - ppublish
SO  - Pain. 2020 Jul;161(7):1584-1596. doi: 10.1097/j.pain.0000000000001855.