scholarly journals NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury

Cell Reports ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2678-2689 ◽  
Author(s):  
Perrine Inquimbert ◽  
Martin Moll ◽  
Alban Latremoliere ◽  
Chi-Kun Tong ◽  
John Whang ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Peripheral Nerve Injury ◽  
Spinal Dorsal Horn ◽  
Receptor Activation ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons ◽  
Nmda Receptor Activation

Convergent Nociceptive Input to Spinal Dorsal Horn Neurons After Peripheral Nerve Injury

2014 ◽  
Vol 40 (3) ◽  
pp. 438-445 ◽  
Author(s):  
Ryuji Terayama ◽  
Noriko Kishimoto ◽  
Yuya Yamamoto ◽  
Kotaro Maruhama ◽  
Hiroki Tsuchiya ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Spinal Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons ◽  
Nociceptive Input

scholarly journals Impaired Glial Glutamate Uptake Induces Extrasynaptic Glutamate Spillover in the Spinal Sensory Synapses of Neuropathic Rats

2010 ◽  
Vol 103 (5) ◽  
pp. 2570-2580 ◽  
Author(s):  
Hui Nie ◽  
Han-Rong Weng
Keyword(s):  
Nmda Receptor ◽  
Dorsal Horn ◽  
Glutamate Receptor ◽  
Synaptic Input ◽  
Spinal Dorsal Horn ◽  
Glutamate Uptake ◽  
Receptor Activation ◽  
Cell Dysfunction ◽  
Spinal Dorsal ◽  
Nmda Receptor Activation

Glial cell dysfunction and excessive glutamate receptor activation in spinal dorsal horn neurons are hallmark mechanisms of pathological pain. The way in which glial cell dysfunction leads to excessive glutamate receptor activation in the spinal sensory synapses remains unknown. We and others recently reported the downregulation of glial glutamate transporter (GT) protein expression in the spinal dorsal horn of neuropathic rats. In this study, we showed that excitatory postsynaptic currents originating from N-methyl-d-aspartate receptor activation (NMDA EPSCs) elicited by peripheral synaptic input in the spinal sensory synapses were enhanced in neuropathic rats with mechanical allodynia induced by partial sciatic nerve ligation. The enhanced NMDA EPSCs were accompanied by an increased proportion of NR2B receptor activation. Physically blocking the extrasynaptic glutamate with dextran or chemically scavenging the glutamate with glutamic-pyruvic transaminase ameliorated the abnormal NMDA EPSCs in neuropathic rats. Pharmacological blockade of glial GTs with dihydrokainic acid enhanced NMDA receptor activation elicited by synaptic input or puffed glutamate in normal control rats, but this effect was precluded in neuropathic rats. Thus extrasynaptic glutamate spillover and extrasynaptic NMDA receptor activation induced by deficient glial glutamate uptake in the synapses resulted in the excessive activation of NMDA receptors in neuropathic rats. It is suggested that extrasynaptic glutamate spillover may be a key synaptic mechanism related to phenotypic alterations induced by nerve injury in the spinal dorsal horn and that glial GTs are potential new targets in the development of analgesics.

scholarly journals Interferon-gamma potentiates NMDA receptor signaling in spinal dorsal horn neurons via microglia–neuron interaction

2016 ◽  
Vol 12 ◽  
pp. 174480691664492 ◽  
Author(s):  
Mayumi Sonekatsu ◽  
Wataru Taniguchi ◽  
Manabu Yamanaka ◽  
Naoko Nishio ◽  
Shunji Tsutsui ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Dorsal Horn ◽  
Interferon Gamma ◽  
Spinal Dorsal Horn ◽  
Receptor Signaling ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Neuron Interaction ◽  
Spinal Dorsal Horn Neurons
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