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HDAC2, but Not HDAC1, Regulates Kv1.2 Expression to Mediate Neuropathic Pain in CCI Rats
In this study we established a chronic constrictive injury (CCI) model and used western blot, quantitative real-time PCR, immunostaining, intrathecal injection, and siRNA methods to explore which HDAC subunit is involved in regulating Kv1.2 expression to mediate NPP. Our results demonstrated that nerve injury led to upregulation of HDAC1 expression in the DRG, and of HDAC2 in the DRG and spinal cord. Double-labeling immunofluorescence histochemistry showed that Kv1.2 principally co-localized with HDAC2, but not HDAC1, in NF200-positive large neurons of the DRG. Intrathecal injection with the HDAC inhibitor, suberoylanilide...
Source: Neuroscience - April 24, 2019 Category: Neuroscience Source Type: research

Role of NaV1.6 and NaVβ4 sodium channel subunits in a rat model of low back pain induced by compression of the dorsal root ganglia
In this study, we used siRNA- mediated knockdown of the pore-forming NaV1.6 and regulatory NaVβ4 sodium channel isoforms that have been previously implicated in a different model of low back pain caused by locally inflaming the L5 DRG. Knockdown of either subunit markedly reduced spontaneous pain and mechanical and cold hypersensitivity induced by DRG compression, and reduced spontaneous activity and hyperexcitability of sensory neurons with action potentials <1.5 msec (predominately cells with myelinated axons, based on conduction velocities measured in a subset of cells) 4 days after DRG compression. These results w...
Source: Neuroscience - January 28, 2019 Category: Neuroscience Source Type: research

Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K
Publication date: 10 August 2018Source: Neuroscience, Volume 385Author(s): Xu Ding, Wei Yang, Xiao-Dan Liu, Xi Yang, Huan-Min Wang, Jun TaiAbstractNeonatal injury-induced exaggeration of pain hypersensitivity after adult trauma is a significant clinical challenge. However, the underlying mechanisms remain poorly understood. Growing evidence shows that spinal Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) contributes to chronic pain in adult rodents. Here we demonstrated that the phosphorylation and expression of SHP2 in synaptosomal fraction of the spinal dorsal horn are elevated in adult rats subje...
Source: Neuroscience - July 10, 2018 Category: Neuroscience Source Type: research

Activity-dependent synaptic recruitment of neuroligin 1 in spinal dorsal horn contributed to inflammatory pain
In this study, we found an activity-dependent regulation of NLGN1 synaptic expression in pain-related spinal cord dorsal horns of mice. The enhancement of neuronal activity by pharmacological activation of NMDA receptor (NMDAR) or removal of GABAergic inhibition in intact mice significantly increased NLGN1 concentration at synaptosomal membrane fraction. Intraplantar injection of complete Freund's adjuvant (CFA) also increased the NLGN1 expression at synapses. NMDAR might act through Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Src-family protein tyrosine kinase member Fyn to induce the synaptic redistribution ...
Source: Neuroscience - July 10, 2018 Category: Neuroscience Source Type: research

Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K
Publication date: 10 August 2018Source: Neuroscience, Volume 385Author(s): Xu Ding, Wei Yang, Xiao-Dan Liu, Xi Yang, Huan-Min Wang, Jun TaiAbstractNeonatal injury-induced exaggeration of pain hypersensitivity after adult trauma is a significant clinical challenge. However, the underlying mechanisms remain poorly understood. Growing evidence shows that spinal Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) contributes to chronic pain in adult rodents. Here we demonstrated that the phosphorylation and expression of SHP2 in synaptosomal fraction of the spinal dorsal horn are elevated in adult rats subje...
Source: Neuroscience - July 5, 2018 Category: Neuroscience Source Type: research

Suppression of Pax2 Attenuates Allodynia and Hyperalgesia through ET-1 –ETAR–NFAT5 Signaling in a Rat Model of Neuropathic Pain
Publication date: 1 August 2018 Source:Neuroscience, Volume 384 Author(s): Lydia Wai Tai, Zhiqiang Pan, Liting Sun, Haobo Li, Pan Gu, Stanley Sau Ching Wong, Sookja K. Chung, Chi Wai Cheung Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, ...
Source: Neuroscience - June 8, 2018 Category: Neuroscience Source Type: research

Increased Neuroligin 2 Levels in the Postsynaptic Membrane in Spinal Dorsal Horn may Contribute to Postoperative Pain
Publication date: 1 July 2018 Source:Neuroscience, Volume 382 Author(s): Ruijuan Guo, Huili Li, Xueyang Li, Yuqing Sun, Huihui Miao, Danxu Ma, Fangxiao Hong, Ye Zhang, Yun Guan, Junfa Li, Ming Tian, Yun Wang Neuroligin 2 is a synaptic cell adhesion molecule that is mainly located in inhibitory synapses and is crucial in the regulation of synapse function through protein–protein interactions. However, researchers have not clearly determined whether neuroligin 2 is involved in the development of postoperative pain. In the current study, Western blot, immunofluorescence staining and co-immunoprecipitation were used to exam...
Source: Neuroscience - May 7, 2018 Category: Neuroscience Source Type: research

Local knockdown of the NaV1.6 sodium channel reduces pain behaviors, sensory neuron excitability, and sympathetic sprouting in rat models of neuropathic pain
In this study, we injected small inhibitory (si) RNA directed against the NaV1.6 sodium channel isoform into the DRG before SNL. This isoform can mediate high-frequency repetitive firing, like that seen in spontaneously active neurons. Local knockdown of NaV1.6 markedly reduced mechanical pain behaviors induced by SNL, reduced sympathetic sprouting into the ligated sensory ganglion, and blocked abnormal spontaneous activity and other measures of hyperexcitability in myelinated neurons in the ligated sensory ganglion. Immunohistochemical experiments showed that sympathetic sprouting preferentially targeted NaV1.6-positive n...
Source: Neuroscience - March 6, 2015 Category: Neuroscience Source Type: research