Augmentation of neuronal excitability by glial cells in the rat spinal dorsal horn under persistent pain state revealed by optical imaging with voltage-sensitive dye

2011 ◽  
Vol 71 ◽  
pp. e159
Author(s):  
Misato Murayama ◽  
Hiroshi Ikeda ◽  
Kazuyuki Murase
Keyword(s):  
Optical Imaging ◽  
Dorsal Horn ◽  
Glial Cells ◽  
Spinal Dorsal Horn ◽  
Neuronal Excitability ◽  
Persistent Pain ◽  
Voltage Sensitive Dye ◽  
Spinal Dorsal ◽  
Pain State

scholarly journals Metabotropic glutamate receptor 5 regulates excitability and Kv4.2-containing K+ channels primarily in excitatory neurons of the spinal dorsal horn

2011 ◽  
Vol 105 (6) ◽  
pp. 3010-3021 ◽  
Author(s):  
Hui-Juan Hu ◽  
Robert W. Gereau
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Neuronal Excitability ◽  
Gabaergic Neurons ◽  
Erk Signaling ◽  
Metabotropic Glutamate ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Excitatory Neurons

Metabotropic glutamate (mGlu) receptors play important roles in the modulation of nociception. Previous studies demonstrated that mGlu5 modulates nociceptive plasticity via activation of ERK signaling. We have reported recently that the Kv4.2 K+ channel subunit underlies A-type currents in spinal cord dorsal horn neurons and that this channel is modulated by mGlu5-ERK signaling. In the present study, we tested the hypothesis that modulation of Kv4.2 by mGlu5 occurs in excitatory spinal dorsal horn neurons. With the use of a transgenic mouse strain expressing enhanced green fluorescent protein (GFP) under control of the promoter for the γ-amino butyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase 67 (GAD67), we found that these GABAergic neurons express less Kv4.2-mediated A-type current than non-GAD67-GFP neurons. Furthermore, the mGlu1/5 agonist, (R,S)-3,5-dihydroxyphenylglycine, had no modulatory effects on A-type currents or neuronal excitability in this subgroup of GABAergic neurons but robustly modulated A-type currents and neuronal excitability in non-GFP-expressing neurons. Immunofluorescence studies revealed that Kv4.2 was highly colocalized with markers of excitatory neurons, such as vesicular glutamate transporter 1/2, PKCγ, and neurokinin 1, in cultured dorsal horn neurons. These results indicate that mGlu5-Kv4.2 signaling is associated with excitatory dorsal horn neurons and suggest that the pronociceptive effects of mGlu5 activation in the spinal cord likely involve enhanced excitability of excitatory neurons.

Liver X Receptor α Is Involved in Counteracting Mechanical Allodynia by Inhibiting Neuroinflammation in the Spinal Dorsal Horn

2017 ◽  
Vol 127 (3) ◽  
pp. 534-547 ◽  
Author(s):  
Jing Xu ◽  
Yi-Wei Feng ◽  
Ling Liu ◽  
Wei Wang ◽  
Xiong-Xiong Zhong ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Glial Cells ◽  
Mechanical Allodynia ◽  
Spinal Dorsal Horn ◽  
Liver X Receptor ◽  
Spared Nerve Injury ◽  
Wild Type ◽  
Spinal Dorsal ◽  
Liver X Receptor Α

Abstract Background Liver X receptors, including α and β isoforms, are ligand-activated transcription factors. Whether liver X receptor α plays a role in neuropathic pain is unknown. Methods A spared nerve injury model was established in adult male rats and mice. Von Frey tests were performed to evaluate the neuropathic pain behavior; Western blot and immunohistochemistry were performed to understand the underlying mechanisms. Results Intrathecal injection of a specific liver X receptor agonist T0901317 or GW3965 could either prevent the development of mechanical allodynia or alleviate the established mechanical allodynia, both in rats and wild-type mice. GW3965 could inhibit the activation of glial cells and the expression of tumor necrosis factor-α (mean ± SD: 196 ± 48 vs. 119 ± 57; n = 6; P < 0.01) and interleukin 1β (mean ± SD: 215 ± 69 vs. 158 ± 74; n = 6; P < 0.01) and increase the expression of interleukin 10 in the spinal dorsal horn. All of the above effects of GW3965 could be abolished by liver X receptor α mutation. Moreover, more glial cells were activated, and more interleukin 1β was released in the spinal dorsal horn in liver X receptor α knockout mice than in wild-type mice after spared nerve injury. Aminoglutethimide, a neurosteroid synthesis inhibitor, blocked the inhibitory effect of T0901317 on mechanical allodynia, on the activation of glial cells, and on the expression of cytokines. Conclusions Activation of liver X receptor α inhibits mechanical allodynia by inhibiting the activation of glial cells and rebalancing cytokines in the spinal dorsal horn via neurosteroids.

scholarly journals Bidirectional Neuron–Glia Interactions Triggered by Deficiency of Glutamate Uptake at Spinal Sensory Synapses

2010 ◽  
Vol 104 (2) ◽  
pp. 713-725 ◽  
Author(s):  
Hui Nie ◽  
Haijun Zhang ◽  
Han-Rong Weng
Keyword(s):  
Dorsal Horn ◽  
Glial Cells ◽  
Synaptic Input ◽  
Spinal Dorsal Horn ◽  
Glutamate Uptake ◽  
Glutamate Transporters ◽  
Spinothalamic Tract ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal

Bidirectional interactions between neurons and glial cells are crucial to the genesis of pathological pain. The mechanisms regulating these interactions and the role of this process in relaying synaptic input in the spinal dorsal horn remain to be established. We studied the role of glutamate transporters in the regulation of such interactions. On pharmacological blockade of glutamate transporters, slow inward currents (SICs) appeared spontaneously and/or were evoked by peripheral synaptic input in the spinal superficial dorsal horn neurons, including the spinothalamic tract neurons. We showed that the SICs were induced by the release of glutamate from glial cells. On inhibition of glutamate uptake, the stimulation-induced, synaptically released glutamate activated glial cells and caused glial cells to release glutamate. Glial-derived glutamate acted on extrasynaptic N-methyl-d-aspartate (NMDA) receptors mainly composed of NR2B receptors and generated SICs, which led to depolarization and action potential generation in superficial spinal dorsal horn neurons. Thus glutamate transporters regulate glutamatergic neuron–glia interactions at spinal sensory synapses. When glutamate uptake is impaired, glial cells function like excitatory interneurons—they are activated by peripheral synaptic input and release glutamate to activate postsynaptic neurons in spinal pain pathways.

scholarly journals Spatial organization of activity evoked by focal stimulation within the rat spinal dorsal horn as visualized by voltage-sensitive dye imaging in the slice

2019 ◽  
Vol 122 (4) ◽  
pp. 1697-1707 ◽  
Author(s):  
Masaharu Mizuno ◽  
Go Kato ◽  
Andrew M. Strassman
Keyword(s):  
White Matter ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Spatial Organization ◽  
Male Rats ◽  
Voltage Sensitive Dye ◽  
Spinal Dorsal ◽  
Medial Dorsal ◽  
Synaptic Responses ◽  
Voltage Sensitive Dye Imaging

In a prior study using laser scanning photostimulation, we found a pronounced cell type-specific mediolateral asymmetry in the local synaptic connectivity in the superficial laminae of the spinal dorsal horn (Kosugi M, Kato G, Lukashov S, Pendse G, Puskar Z, Kozsurek M, Strassman AM. J Physiol 591: 1935–1949, 2013). To obtain information on dorsal horn organization that might complement findings from microelectrode studies, voltage-sensitive dye imaging was used in the present study to examine patterns of activity evoked by focal electrical stimulation, in the presence and absence of synaptic blocking agents, at different positions in transverse, parasagittal, and horizontal slices of the dorsal horn of 2- to 3-wk -old male rats. A pronounced difference in responsiveness was found between medial and lateral dorsal horn, in that medial sites in the superficial dorsal horn showed much larger synaptic responses to focal stimulation than lateral sites. This difference appeared to be a result of a difference in the intrinsic elements of the dorsal horn, rather than a difference in the inputs from the white matter, because the stimulus intensities were subthreshold for evoking synaptic responses from stimulation at sites in the white matter, although it is also possible that the greater responsiveness is due, at least in part, to activation of Aβ primary afferent fibers that pass through the medial dorsal horn. The results raise the possibility of differences between medial and dorsal horn that need to be taken into account in the interpretation of studies of dorsal horn organization. NEW & NOTEWORTHY We used voltage-sensitive dye imaging to obtain information on spatial aspects of dorsal horn organization that are difficult to examine with single-cell approaches because of the limitations of microelectrode sampling. The most noteworthy finding was a previously unreported, extreme difference between medial and lateral dorsal horn in responsiveness to focal stimulation that appears to result, at least in part, from a greater degree of excitability or local connectivity in medial dorsal horn.

Differential Changes in Neuronal Excitability in the Spinal Dorsal Horn After Spinal Nerve Ligation in Rats

2016 ◽  
Vol 41 (11) ◽  
pp. 2880-2889 ◽  
Author(s):  
Ryuji Terayama ◽  
Yuya Yamamoto ◽  
Noriko Kishimoto ◽  
Mitsuyasu Tabata ◽  
Kotaro Maruhama ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Neuronal Excitability ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Spinal Dorsal
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