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14-3-3 γ mediates the long-term inhibition of peripheral kappa opioid receptor antinociceptive signaling by norbinaltorphimine
Neuropharmacology. 2022 Sep 17:109251. doi: 10.1016/j.neuropharm.2022.109251. Online ahead of print.ABSTRACTLong-term inhibition of kappa opioid receptor (KOR) signaling in peripheral pain-sensing neurons is a potential obstacle for development of peripherally-restricted KOR agonists that produce analgesia. Such a long-term inhibitory mechanism is invoked from activation of c-Jun N-terminal kinase (JNK) that follows a single injection of the KOR antagonist norbinaltorphimine (norBNI). This effect requires protein synthesis of an unknown mediator in peripheral pain-sensing neurons. Using 2D difference gel electrophoresis wi...
Source: Neuropharmacology - September 20, 2022 Category: Drugs & Pharmacology Authors: Michael J Wedemeyer Elaine M Jennings Hudson R Smith Teresa S Chavera Raehannah J Jamshidi Kelly A Berg William P Clarke Source Type: research

LncRNA MRAK159688 facilitates morphine tolerance by promoting REST-mediated inhibition of mu opioid receptor in rats
Neuropharmacology. 2022 Jan 1;206:108938. doi: 10.1016/j.neuropharm.2021.108938. Online ahead of print.ABSTRACTMorphine tolerance (MT) caused by the long-term use of morphine is a major medical problem. The molecular mechanism of morphine tolerance remains elusive. Here, we established a morphine tolerance model in rats and verified whether the long noncoding RNA (lncRNA) MRAK159688 is involved in morphine tolerance and its specific molecular mechanism. We show the significant upregulation of MRAK159688 expression in the spinal cord of morphine-tolerant rats. Overexpression of MRAK159688 by a lentivirus reduces the analges...
Source: Neuropharmacology - January 4, 2022 Category: Drugs & Pharmacology Authors: Meiling Deng Zengli Zhang Manyu Xing Xia Liang Zhengyiqi Li Jing Wu Shasha Jiang Yingqi Weng Qulian Guo Wangyuan Zou Source Type: research

Downregulation of ClC-3 in dorsal root ganglia neurons contributes to mechanical hypersensitivity following peripheral nerve injury.
Abstract ClC-3 chloride channel/antiporter has been demonstrated to play an important role in synaptic transmission in central nervous system. However, its expression and function in sensory neurons is poorly understood. In present work, we found that ClC-3 is expressed at high levels in dorsal root ganglia (DRG). Co-immunofluorescent data showed that ClC-3 is mainly distributed in A- and C-type nociceptive neurons. ClC-3 expression in DRG is decreased in the spared nerve injury (SNI) model of neuropathic pain. Knockdown of local ClC-3 in DRG neurons with siRNA increased mechanical sensitivity in naïve rats, whil...
Source: Neuropharmacology - July 22, 2016 Category: Drugs & Pharmacology Authors: Pang RP, Xie MX, Yang J, Shen KF, Chen X, Su YX, Yang C, Tao J, Liang SJ, Zhou JG, Zhu HQ, Wei XH, Li YY, Qin ZH, Liu XG Tags: Neuropharmacology Source Type: research

Geniposide and its iridoid analogs exhibit antinociception by acting at the spinal GLP-1 receptors.
This study evaluated the antinociceptive activities of geniposide, a presumed small molecule GLP-1R agonist. Geniposide produced concentration-dependent, complete protection against hydrogen peroxide-induced oxidative damage in PC12 and HEK293 cells expressing rat and human GLP-1Rs, but not in HEK293T cells that do not express GLP-1Rs. The orthosteric GLP-1R antagonist exendin(9-39) right-shifted the concentration-response curve of geniposide without changing the maximal protection, with identical pA2 values in both cell lines. Subcutaneous and oral geniposide dose-dependently blocked the formalin-induced tonic response bu...
Source: Neuropharmacology - April 17, 2014 Category: Drugs & Pharmacology Authors: Gong N, Fan H, Ma AN, Xiao Q, Wang YX Tags: Neuropharmacology Source Type: research