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MicroRNA-146a-5p attenuates visceral hypersensitivity through targeting chemokine CCL8 in the spinal cord in a mouse model of colitis.
In this study, we aimed to explore the potential role of miR-146a-5p (the mature form of miR-146a) in a mouse model of colitis induced by intracolonic injection of trinitrobenzene sulfonic acid (TNBS). We found that induction of colitis resulted in visceral hyperalgesia manifested by a decreased pain threshold to colorectal distension and upregulation of miR-146a-5p expression in the lumbosacral spinal cord. In situ hybridization and immunohistochemistry results showed that miR-146a-5p was colocalized with neuronal marker NeuN, but not with astrocytic marker GFAP or microglial marker IBA-1. Dual-luciferase reporter assay s...
Source: Brain Research Bulletin - March 14, 2018 Category: Neurology Authors: Lu Y, Cao DL, Zhao LX, Han Y, Zhang YL Tags: Brain Res Bull Source Type: research

PKM2 is involved in neuropathic pain by regulating ERK and STAT3 activation in rat spinal cord
ConclusionOur findings demonstrate that inhibiting PKM2 expression effectively attenuates CCI-induced neuropathic pain and inflammatory responses in rats, possibly through regulating ERK and STAT3 signaling pathway.
Source: The Journal of Headache and Pain - January 18, 2018 Category: Neurology Source Type: research

AKAP150 involved in paclitaxel-induced neuropathic pain via inhibiting CN/NFAT2 pathway and downregulating IL-4
In this study, we found that A-kinase anchor protein 150 (AKAP150) was significantly upregulated after paclitaxel injection. Inhibition of AKAP150 via siRNA or AKAP150flox/flox in rodents alleviated the pain behavior induced by paclitaxel, and partly restored the decreased calcineurin (CN) phosphatase activity after paclitaxel treatment. Paclitaxel decreased the expression of anti-inflammatory cytokine interleukin-4 (IL-4), and intrathecal injections of IL-4 effectively alleviated paclitaxel-induced hypersensitivity and the frequency of dorsal root ganglion (DRG) neurons action potential. The decreased CN enzyme activity, ...
Source: Brain, Behavior, and Immunity - January 11, 2018 Category: Neurology Source Type: research

Downregulation of spinal astrocytic connexin43 leads to upregulation of interleukin ‐6 and cyclooxygenase‐2 and mechanical hypersensitivity in mice
Abstract Connexin43 (Cx43), involved in intercellular signaling, is expressed in spinal dorsal horn astrocytes and crucial in the maintenance of neuropathic pain. Downregulation of spinal astrocytic Cx43 in mice enhances glutamatergic neurotransmission by decreasing glutamate transporter GLT‐1 expression, resulting in cutaneous hypersensitivity. Decreased expression of astrocytic Cx43 could lead to altered expression of other nociceptive molecules. Transfection of Cx43‐targeting siRNA in cultured spinal astrocytes increased expression of the pronociceptive cytokine interleukin‐6 (IL‐6) and the prostaglandin synthes...
Source: Glia - November 6, 2017 Category: Neurology Authors: Norimitsu Morioka, Shiori Fujii, Syun Kondo, Fang Fang Zhang, Kazuki Miyauchi, Yoki Nakamura, Kazue Hisaoka ‐Nakashima, Yoshihiro Nakata Tags: RESEARCH ARTICLE Source Type: research

AKAP150 involved in Paclitaxel-Induced Neuropathic Pain via Inhibiting CN/NFAT2 pathway and downregulating IL-4.
In this study, we found that A-kinase anchor protein 150 (AKAP150) was significantly upregulated after paclitaxel injection. Inhibition of AKAP150 via siRNA or AKAP150(flox/flox) in rodents alleviated the pain behavior induced by paclitaxel, and partly restored the decreased calcineurin (CN) phosphatase activity after paclitaxel treatment. Paclitaxel decreased the expression of anti-inflammatory cytokine interleukin-4 (IL-4), and intrathecal injections of IL-4 effectively alleviated paclitaxel-induced hypersensitivity and the frequency of dorsal root ganglion (DRG) neurons action potential. The decreased CN enzyme activity...
Source: Brain, Behavior, and Immunity - October 19, 2017 Category: Neurology Authors: Nie B, Liu C, Bai X, Chen X, Wu S, Zhang S, Huang Z, Xie M, Xu T, Xin W, Zeng W, Ouyang H Tags: Brain Behav Immun Source Type: research

LncRNA NONRATT021972 Was Associated with Neuropathic Pain Scoring in Patients with Type 2 Diabetes.
CONCLUSION: LncRNA NONRATT021972 increased in type 2 diabetes and was positively associated with neuropathic pain scoring in type 2 diabetes. LncRNA NONRATT021972 exacerbated neuropathic pain via TNF-α related pathways. PMID: 28928602 [PubMed - in process]
Source: Behavioural Neurology - September 22, 2017 Category: Neurology Authors: Yu W, Zhao GQ, Cao RJ, Zhu ZH, Li K Tags: Behav Neurol Source Type: research

Downregulations of TRPM8 expression and membrane trafficking in dorsal root ganglion mediate the attenuation of cold hyperalgesia in CCI rats induced by GFR α3 knockdown.
CONCLUSION: Our results demonstrate that GFRα3 knockdown specially inhibits cold hyperalgesia following CCI via decreasing the expression level and plasma membrane trafficking of TRPM8 in DRG. GFRα3 and its downstream mediator, TRPM8, represent a new analgesia axis which can be further exploited in sensitized cold reflex under the condition of chronic pain. PMID: 28867384 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - August 31, 2017 Category: Neurology Authors: Su L, Shu R, Song C, Yu Y, Wang G, Li Y, Liu C Tags: Brain Res Bull Source Type: research

Cynandione A attenuates neuropathic pain through p38 β MAPK-mediated spinal microglial expression of β-endorphin
This study aims to evaluate the antihypersensitivity activities of cynandione A in neuropathy and explored its mechanisms of action. Intrathecal injection of cynandione A dose-dependently attenuated spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia, with maximal possible effects of 57% and 59%, ED50s of 14.9 μg and 6.5 μg, respectively. Intrathecal injection of cynandione A significantly increased β-endorphin levels in spinal cords of neuropathic rats and its treatment concentration-dependently induced β-endorphin expression in cultured primary microglia (but not in neurons or astrocytes), wit...
Source: Brain, Behavior, and Immunity - February 8, 2017 Category: Neurology Source Type: research

Cynandione A attenuates neuropathic pain through p38 β MAPK-mediated spinal microglial expression of β-endorphin.
This study aims to evaluate the antihypersensitivity activities of cynandione A in neuropathy and explored its mechanisms of action. Intrathecal injection of cynandione A dose-dependently attenuated spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia, with maximal possible effects of 57% and 59%, ED50s of 14.9 μg and 6.5 μg, respectively. Intrathecal injection of cynandione A significantly increased β-endorphin levels in spinal cords of neuropathic rats and its treatment concentration-dependently induced β-endorphin expression in cultured primary microglia (but not in neurons or astrocytes), wit...
Source: Brain, Behavior, and Immunity - February 7, 2017 Category: Neurology Authors: Huang Q, Mao XF, Wu HY, Liu H, Sun ML, Wang X, Wang YX Tags: Brain Behav Immun Source Type: research

Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice.
Abstract Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared...
Source: Experimental Neurology - February 4, 2017 Category: Neurology Authors: Lin YT, Liu HL, Day YJ, Chang CC, Hsu PH, Chen JC Tags: Exp Neurol Source Type: research

Neuronal Fc-epsilon receptor I contributes to antigen-evoked pruritus in a murine model of ocular allergy.
This study may suggest a novel mechanism for the development of pathological itch in allergic diseases. PMID: 27865948 [PubMed - as supplied by publisher]
Source: Brain, Behavior, and Immunity - November 15, 2016 Category: Neurology Authors: Liu F, Xu L, Chen N, Zhou M, Li C, Yang Q, Xie Y, Huang Y, Ma C Tags: Brain Behav Immun Source Type: research

Neuronal Fc-epsilon receptor I contributes to antigen-evoked pruritus in a murine model of ocular allergy
This study may suggest a novel mechanism for the development of pathological itch in allergic diseases.
Source: Brain, Behavior, and Immunity - November 15, 2016 Category: Neurology Source Type: research

lncRNA NONRATT021972 siRNA Decreases Diabetic Neuropathic Pain Mediated by the P2X 3 Receptor in Dorsal Root Ganglia
Abstract Long noncoding RNAs (lncRNAs) participate in physiological and pathophysiological processes. Type 2 diabetes mellitus (T2DM) accounts for more than 90 % of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. The aim of this study was to investigate the effects of lncRNA NONRATT021972 small interference RNA (siRNA) on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). These experiments showed that the expression levels of NONRATT021972 in DRG were increased in the T2DM rat model (intraperitoneal injection of STZ with 30 mg/kg). The concentra...
Source: Molecular Neurobiology - January 7, 2016 Category: Neurology Source Type: research

Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice
Publication date: Available online 24 June 2015 Source:Brain, Behavior, and Immunity Author(s): Norimitsu Morioka , Fang Fang Zhang , Yoki Nakamura , Tomoya Kitamura , Kazue Hisaoka-Nakashima , Yoshihiro Nakata Spinal cord astrocytes are critical in the maintenance of neuropathic pain. Connexin 43 (Cx43) expressed on spinal dorsal horn astrocytes modulates synaptic neurotransmission, but its role in nociceptive transduction has yet to be fully elaborated. In mice, Cx43 is mainly expressed in astrocytes, not neurons or microglia, in the spinal dorsal horn. Hind paw mechanical hypersensitivity was observed beginning 3days ...
Source: Brain, Behavior, and Immunity - July 3, 2015 Category: Neurology Source Type: research

Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice.
Abstract Spinal cord astrocytes are critical in the maintenance of neuropathic pain. Connexin 43 (Cx43) expressed on spinal dorsal horn astrocytes modulates synaptic neurotransmission, but its role in nociceptive transduction has yet to be fully elaborated. In mice, Cx43 is mainly expressed in astrocytes, not neurons or microglia, in the spinal dorsal horn. Hind paw mechanical hypersensitivity was observed beginning 3 days after partial sciatic nerve ligation (PSNL), but a persistent downregulation of astrocytic Cx43 in ipsilateral lumbar spinal dorsal horn was not observed until 7 days post-PSNL, suggesting that ...
Source: Brain, Behavior, and Immunity - June 23, 2015 Category: Neurology Authors: Morioka N, Zhang FF, Nakamura Y, Kitamura T, Hisaoka-Nakashima K, Nakata Y Tags: Brain Behav Immun Source Type: research

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