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Therapy: Pain Management

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Total 31 results found since Jan 2013.

CREB Participates in Paclitaxel-Induced Neuropathic Pain Genesis Through Transcriptional Activation of Dnmt3a in Primary Sensory Neurons
AbstractChemotherapy-induced peripheral neuropathic pain (CIPNP) often occurs in cancer patients treated with antineoplastic drugs. Therapeutic management of CIPNP is very limited, at least in part due to the largely unknown mechanisms that underlie CIPNP genesis. Here, we showed that systemic administration of the chemotherapeutic drug paclitaxel significantly and time-dependently increased the levels of cyclic AMP response element-binding protein (CREB) in dorsal root ganglion (DRG) neurons. Blocking this increase through DRG microinjection ofCreb siRNA attenuated paclitaxel-induced mechanical, heat, and cold nociceptive...
Source: Neurotherapeutics - October 13, 2020 Category: Neurology Source Type: research

Porphyric Neuropathy: Pathophysiology, Diagnosis, and Updated Management
AbstractPurpose of ReviewTo review the peripheral neurological complications of the acute hepatic porphyrias, as well as the latest advances in their pathophysiology and management.Recent FindingsThe diagnosis of porphyric neuropathy remains challenging as varying neuropathic patterns are encountered depending on disease stage, including a non-length-dependent distribution pattern. The major pathophysiologic mechanism is δ-aminolevulinic acid (ALA)–induced neurotoxicity. The less restrictive blood-nerve barrier in the autonomic ganglia and myenteric plexus may explain the frequency of dysautonomic manifestations. Recent...
Source: Current Neurology and Neuroscience Reports - October 6, 2020 Category: Neuroscience Source Type: research

Epigenetic Restoration of Voltage ‐gated Potassium Channel Kv1.2 Alleviates Nerve Injury‐induced Neuropathic Pain
AbstractVoltage ‐gated potassium channels (Kv) are important regulators of neuronal excitability for its role of regulating resting membrane potential and repolarization. Recent studies show that Kv channels participate in neuropathic pain, but the detailed underlying mechanisms are far from being clear. In the c urrent study, we used siRNA, miR‐137 agomir and antagomir to regulate the expression of Kv1.2 in spinal cord and dorsal root ganglia (DRG) of naïve and chronic constriction injury (CCI) rats. Kv currents and neuron excitability in DRG neurons were examined by patch‐clamp whole‐cell recording to verify the...
Source: Journal of Neurochemistry - July 2, 2020 Category: Neuroscience Authors: Jingjing Zhang, Lina Rong, Jinping Shao, Yidan Zhang, Yaping Liu, Sen Zhao, Lei Li, Wenli Yu, Mengya Zhang, Xiuhua Ren, Qingzan Zhao, Changlian Zhu, Huan Luo, Weidong Zang, Jing Cao Tags: ORIGINAL ARTICLE Source Type: research

A Bcr-Abl Inhibitor GNF-2 Attenuates Inflammatory Activation of Glia and Chronic Pain
GNF-2 is an allosteric inhibitor of Bcr-Abl. It was developed as a new class of anti-cancer drug to treat resistant chronic myelogenous leukemia. Recent studies suggest that c-Abl inhibition would provide a neuroprotective effect in animal models of Parkinson’s disease as well as in clinical trials. However, the role of c-Abl and effects of GNF-2 in glia-mediated neuroinflammation or pain hypersensitivity has not been investigated. Thus, in the present study, we tested the hypothesis that c-Abl inhibition by GNF-2 may attenuate the inflammatory activation of glia and the ensuing pain behaviors in animal models. Our resul...
Source: Frontiers in Pharmacology - May 19, 2019 Category: Drugs & Pharmacology Source Type: research

Cannabinoid Receptor 2 Agonist JWH-015 Inhibits Interleukin-1 β-Induced Inflammation in Rheumatoid Arthritis Synovial Fibroblasts and in Adjuvant Induced Arthritis Rat via Glucocorticoid Receptor
Management of pain in the treatment of rheumatoid arthritis (RA) is a priority that is not fully addressed by the conventional therapies. In the present study, we evaluated the efficacy of cannabinoid receptor 2 (CB2) agonist JWH-015 using RA synovial fibroblasts (RASFs) obtained from patients diagnosed with RA and in a rat adjuvant-induced arthritis (AIA) model of RA. Pretreatment of human RASFs with JWH-015 (10-20 µM) markedly inhibited the ability of pro-inflammatory cytokine interleukin-1β (IL-1β) to induce production of IL-6 and IL-8 and cellular expression of inflammatory cyclooxygenase-2 (COX-2). JWH-015 was effe...
Source: Frontiers in Immunology - May 7, 2019 Category: Allergy & Immunology Source Type: research

Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 23, 2019 Category: Cancer & Oncology Source Type: research

Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy. Ethics Statement All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007). Author Contributions H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Ropivacaine regulates the expression and function of heme oxygenase-1
Publication date: July 2018 Source:Biomedicine & Pharmacotherapy, Volume 103 Author(s): Xiangbiao Yan, Yu Li, Xuechang Han, Xu Dong, Yajie Zhang, Qunzhi Xing As a new generation of amide-type local anesthetics (LAs), ropivacaine has been widely used for pain management in clinical settings. Increasing evidence has shown that administration of ropivacaine causes cytotoxic effects and apoptosis. However, the underlying molecular mechanisms still need to be elucidated. In the current study, our results indicated that ropivacaine treatment caused a significant induction of heme oxygenase-1 (HO-1) at both the mRNA and ...
Source: Biomedicine and Pharmacotherapy - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Water-Soluble Polymer Assists N-Methyl-D-Aspartic Acid Receptor 2B siRNA Delivery to Relieve Chronic Inflammatory Pain In Vitro and In Vivo.
Abstract We constructed a water-soluble lipopolymer (WSLP) as a nonviral gene carrier to deliver siRNA targeting NR2B. The cytotoxicity and serum stability of WSLP loaded with siRNA were evaluated, and the knockdown efficiency of WSLP/NR2B-siRNA in PC12 cells was examined. The results showed that WSLP could protect the loading siRNAs from enzymatic degradation in serum and exhibit low cytotoxicity to cells. After transfection, WSLP/NR2B-siRNA complexes reduced the NR2B transcriptional level by 50% and protein level by 55% compared to control siRNA. Moreover, 3 days after intrathecal injection of WSLP/NR2B-siRNA co...
Source: Pain Research and Management - April 8, 2018 Category: Anesthesiology Authors: Peng J, Ma J, Yang X, He H, Wu H, Ma T, Lu J Tags: Pain Res Manag Source Type: research

Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity.
Abstract The local anaesthetics (LAs) are widely used for peripheral nerve blocks, epidural anaesthesia, spinal anaesthesia and pain management. However, exposure to LAs for long duration or at high dosage can provoke potential neuronal damages. Autophagy is an intracellular bulk degradation process for proteins and organelles. However, both the effects of LAs on autophagy in neuronal cells and the effects of autophagy on LAs neurotoxicity are not clear. To answer these questions, both lipid LAs (procaine and tetracaine) and amide LAs (bupivacaine, lidocaine and ropivacaine) were administrated to human neuroblasto...
Source: J Cell Mol Med - November 14, 2016 Category: Molecular Biology Authors: Xiong J, Kong Q, Dai L, Ma H, Cao X, Liu L, Ding Z Tags: J Cell Mol Med Source Type: research

Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity
Abstract The local anaesthetics (LAs) are widely used for peripheral nerve blocks, epidural anaesthesia, spinal anaesthesia and pain management. However, exposure to LAs for long duration or at high dosage can provoke potential neuronal damages. Autophagy is an intracellular bulk degradation process for proteins and organelles. However, both the effects of LAs on autophagy in neuronal cells and the effects of autophagy on LAs neurotoxicity are not clear. To answer these questions, both lipid LAs (procaine and tetracaine) and amide LAs (bupivacaine, lidocaine and ropivacaine) were administrated to human neuroblastoma SH‐S...
Source: Journal of Cellular and Molecular Medicine - October 31, 2016 Category: Molecular Biology Authors: Jingwei Xiong, Qiuyue Kong, Leyang Dai, He Ma, Xiaofei Cao, Li Liu, Zhengnian Ding Tags: Original Article Source Type: research

Functional inhibition of chemokine receptor CCR2 by dicer-substrate-siRNA prevents pain development
Conclusion Altogether, these results validate CCR2 as a an appropriate molecular target for pain control and demonstrate that RNAi-based gene therapy represent an highly specific alternative to classical pharmacological approaches to treat central pathologies such as chronic pain.
Source: Molecular Pain - June 14, 2016 Category: Molecular Biology Authors: Begin-Lavallee, V., Midavaine, E., Dansereau, M.-A., Tetreault, P., Longpre, J.-M., Jacobi, A. M., Rose, S. D., Behlke, M. A., Beaudet, N., Sarret, P. Tags: Research Article Source Type: research

c-Fos-Regulated Matrix Metalloproteinase-9 Expression is Involved in 17ß-Estradiol-Promoted Invasion of Human Endometrial Stromal Cell.
This study investigates the effect of 17β-estradiol (E2) on human endometrial stromal cell (HESC) invasion and the role of c-fos and matrix metalloproteinase-9 (MMP-9) in mediating the biological function of 17β-E2. It is found that 17β-E2 promotes not only HESC invasion, but also c-fos and MMP-9 expression in HESC. Further experiments demonstrate that the estrogen receptor inhibitor ICI 182780 and siRNA-mediated c-fos or MMP-9 knockdown are able to block the effect of 17β-E2 on HESC invasion. Moreover, siRNA-mediated c-fos knockdown suppresses the effect of 17β-E2 on MMP-9 expression. Our results indicate that 17β-E...
Source: Current Molecular Medicine - February 25, 2016 Category: Molecular Biology Authors: Pan H, Zhang P, Li JR, Wang H, Jin MF, Feng C, Huang HF Tags: Curr Mol Med Source Type: research

Therapeutic potential of RNA interference in pain medicine.
Authors: Tan PH, Yang LC, Ji RR Abstract In recent years RNA interference (RNAi) has rapidly become the most widely used tool for gene knockdown due to its high specificity and potency. RNAi is an evolutionarily conserved mechanism for silencing gene expression by targeted degradation of mRNA. In the past decade, hundreds of molecular targets have been identified for their roles in pain modulation. But most molecular targets are not readily druggable with small molecules. RNAi represents a therapeutic approach applicable to these non-druggable targets. There is a rapid increase in the number of studies that use sma...
Source: Open Pain Journal - June 4, 2015 Category: Anesthesiology Tags: Open Pain J 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