scholarly journals Interleukin-17 regulates neuron-glial communications, inhibitory synaptic transmission and neuropathic pain after chemotherapy

2018 ◽  
Author(s):  
Hao Luo ◽  
Hui-Zhu Liu ◽  
Xin Luo ◽  
Sangsu Bang ◽  
Zi-Long Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Synaptic Transmission ◽  
Interleukin 17 ◽  
Patch Clamp Recording ◽  
Satellite Glial Cells ◽  
Inhibitory Synaptic Transmission ◽  
Pain Transmission ◽  
Peripheral Neuron ◽  
Pain Regulation

AbstractThe proinflammatory cytokine Interleukin-17 (IL-17) is produced mainly by Th17 cells and has been implicated in pain regulation. However, synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We observed respective expression of IL-17 and its receptor IL-17R in spinal cord astrocytes and neurons. Patch clamp recording in spinal cord slices revealed that IL-17 not only enhanced EPSCs but also suppressed IPSCs and GABA-induced currents in lamina IIo somatostatin-expressing neurons. Spinal IL-17 was upregulated after paclitaxel treatment, and intrathecal IL-17R blockade reduced paclitaxel-induced neuropathic pain. In dorsal root ganglia, respective IL-17 and IL-17R expression in satellite glial cells and neurons was sufficient and required for inducing neuronal hyperexcitability after paclitaxel. Together, our data show that IL-17/IL-17R mediate both central and peripheral neuron-glial interactions in chemotherapy-induced peripheral neuropathy.

scholarly journals Dynamic effects of TNF-α on synaptic transmission in mice over time following sciatic nerve chronic constriction injury

2013 ◽  
Vol 110 (7) ◽  
pp. 1663-1671 ◽  
Author(s):  
Hongmei Zhang ◽  
Haijun Zhang ◽  
Patrick M. Dougherty
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Chronic Constriction Injury ◽  
Synaptic Signaling ◽  
Tnf Α ◽  
Over Time

Nerve injury-induced central sensitization can manifest as an increase in excitatory synaptic transmission and/or as a decrease in inhibitory synaptic transmission in spinal dorsal horn neurons. Cytokines such as tumor necrosis factor-α (TNF-α) are induced in the spinal cord under various injury conditions and contribute to neuropathic pain. In this study we examined the effect of TNF-α in modulating excitatory and inhibitory synaptic input to spinal substantia gelatinosa (SG) neurons over time in mice following chronic constriction injury (CCI) of the sciatic nerve. Whole cell patch-clamp studies from SG neurons showed that TNF-α enhanced overall excitability of the spinal cord early in time following nerve injury 3 days after CCI compared with that in sham control mice. In contrast, the effects of TNF were blunted 14 days after CCI in nerve-injured mice compared with sham surgery mice. Immunohistochemical staining showed that the expression of TNF-α receptor 1 (TNFR1) was increased at 3 days but decreased at 14 days following CCI in the ipsilateral vs. the contralateral spinal cord dorsal horn. These results suggest that TNF-α acting at TNFR1 is important in the development of neuropathic pain by facilitating excitatory synaptic signaling in the acute phases after nerve injury but has a reduced effect on spinal neuron signaling in the later phases of nerve injury-induced pain. Failure of the facilatory effects of TNF-α on excitatory synaptic signaling in the dorsal horn to resolve following nerve injury may be an important component in the transition between acute and chronic pain conditions.

scholarly journals Effect of galanin on excitatory and inhibitory synaptic transmission in substantia gelatinosa neurons of rat spinal cord slices

PAIN RESEARCH ◽  
2010 ◽  
Vol 25 (3) ◽  
pp. 159-169
Author(s):  
Hai-Yuan Yue ◽  
Tsugumi Fujita ◽  
Lian-Hua Piao ◽  
Takahiro Aoyama ◽  
Satoko Uemura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Substantia Gelatinosa ◽  
Rat Spinal Cord ◽  
Inhibitory Synaptic Transmission

Quantal synaptic transmission in phrenic motor nucleus

1992 ◽  
Vol 68 (4) ◽  
pp. 1468-1471 ◽  
Author(s):  
G. Liu ◽  
J. L. Feldman
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Amplitude Distribution ◽  
Excitatory Synaptic Transmission ◽  
Neonatal Rat ◽  
Respiratory Neurons ◽  
Motor Nucleus ◽  
Patch Clamp Recording ◽  
Epsc Amplitude ◽  
Quantal Size

1. The quantal nature of excitatory synaptic transmission was studied in respiratory interneurons and phrenic motoneurons of intact neonatal rat brain stem-spinal cord preparations in vitro. Synaptic currents were recorded with whole-cell patch-clamp recording techniques. 2. Because the most important factor for quantal detection is the ratio of quantal size to quantal standard deviation, factors that influence this ratio were evaluated so that experimental techniques that enhance this ratio could be defined. 3. Under favorable conditions, we directly observed quantal amplitude fluctuations in spontaneous excitatory postsynaptic currents (EPSCs) in spinal cord respiratory neurons. The quantal conductance size was 55-100 pS. With fast decay of these EPSCs, the charge reaching the soma for a single quantum is only approximately 15 fC (Vh = -80 mV). 4. We also studied miniature EPSC amplitude distributions. These were skewed, as previously reported; however, distinct quantal intervals were observed. Furthermore, in three cells tested, the quantal size in the miniature EPSC amplitude distribution was similar to the quantal size in the spontaneous EPSC amplitude distribution. 5. We conclude that excitatory synaptic transmission in the mammalian spinal cord is quantal and that the apparent skewness of miniature EPSC distributions results from summation of events with multiple quantal peak amplitudes.

scholarly journals Regulation of Inhibitory Synaptic Transmission by Vasoactive Intestinal Peptide (VIP) in the Mouse Suprachiasmatic Nucleus

2003 ◽  
Vol 90 (3) ◽  
pp. 1589-1597 ◽  
Author(s):  
Jason Itri ◽  
Christopher S. Colwell
Keyword(s):  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Kinetic Parameters ◽  
Mean Amplitude ◽  
Dependent Manner ◽  
Patch Clamp Recording ◽  
Inhibitory Synaptic Transmission ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
The Mean

Circadian rhythmicity in mammals is generated by a pair of nuclei in the anterior hypothalamus known as the suprachiasmatic nuclei (SCN), whose neurons express a variety of neuropeptides that are thought to play an important role in the circadian timing system. To evaluate the influence of VIP on inhibitory synaptic transmission between SCN neurons, we used whole cell patch-clamp recording in an acute brain slice preparation of mouse SCN. Baseline spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) varied significantly between regions and across phases, with a greater frequency of IPSCs observed in the dorsomedial region during the early night. Bath-applied VIP caused a significant increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) in a reversible and dose-dependent manner with no effect on the mean amplitude or kinetic parameters. The effect of VIP was widespread throughout the SCN and observed in both ventrolateral (VL) and dorsomedial (DM) regions. In the presence of tetrodotoxin, VIP increased the frequency of miniature IPSCs without affecting the mean magnitude or kinetic parameters. The magnitude of the enhancement by VIP was significantly larger during the day than during the night. Pretreatment with the VIP-PACAP receptor antagonist [Ac-Tyr1, D-Phe2]-GHRF 1-29 or the selective VPAC2 receptor antagonist PG 99-465 completely blocked the VIP-induced enhancement. The effect of VIP appears to be mediated by a cAMP/PKA-dependent mechanism as forskolin mimics, while the PKA antagonist H-89 blocks the observed enhancement of GABA currents. Our data suggest that VIP activates presynaptic VPAC2 receptors to regulate inhibitory synaptic transmission within the SCN and that this effect varies from day to night.

scholarly journals Changes in synaptic transmission of substantia gelatinosa neurons after spinal cord hemisection revealed by analysis using in vivo patch-clamp recording

2016 ◽  
Vol 12 ◽  
pp. 174480691666582 ◽  
Author(s):  
Yuji Kozuka ◽  
Mikito Kawamata ◽  
Hidemasa Furue ◽  
Takashi Ishida ◽  
Satoshi Tanaka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Patch Clamp ◽  
Synaptic Transmission ◽  
Substantia Gelatinosa ◽  
Patch Clamp Recording ◽  
Spinal Cord Hemisection
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