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Condition: Pain

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Total 374 results found since Jan 2013.

BDNF Participates in Chronic Constriction Injury-Induced Neuropathic Pain via Transcriptionally Activating P2X 7 in Primary Sensory Neurons
In this study, we demonstrated that the expression level of brain-derived neurotrophic factor (BDNF) was remarkably and time-dependently increased in dorsal root ganglion (DRG) neurons. DRG microinjection of BDNF siRNA in DRG ameliorated chronic constriction injury (CCI) induced mechanical, thermal, and cold nociceptive hypersensitivities. Overexpressing BDNF through microinjection of the AAV5-BDNF in DRG caused enhanced responses to basal mechanical, thermal, and cold stimuli in mice exposed to CCI. Mechanically, the P2X7 promoter activity was enhanced by CCI-induced increase of DRG BDNF protein and was involved in the CC...
Source: Molecular Neurobiology - May 7, 2021 Category: Neurology Source Type: research

Long noncoding RNA LOC100911498 is a novel regulator of neuropathic pain in rats
ConclusionOur study indicated the effects lncRNA LOC100911498 siRNA exerted on NP were mediated by P2X4R on microglia in the spinal cords of rats. Further, LOC100911498 may be a novel positive regulator of NP by regulating the expression and function of the P2X4R.
Source: Brain and Behavior - May 5, 2021 Category: Neurology Authors: Wenxin Tang, Lufeng Zhang, Zhisong Li Tags: ORIGINAL RESEARCH Source Type: research

Development of lipid nanoparticles for delivery of siRNA to neural cells
Lipid nanoparticles (LNPs) are a clinically approved platform to deliver siRNA to the liver. We are optimizing this platform to deliver siRNA for the treatment of pain. siRNA against TRPV1 (siTRPV1) was chosen as a proof of concept. siTRPV1-LNPs were formulated using C12-200, an ionizable cationic lipid and helper lipids. Their particle size and surface charge was characterized using dynamic light scattering and siRNA encapsulation efficiency was determined using a Ribogreen assay. A panel of breast cancer cell lines (MCF-7, MDA-MB-231 and BT-549) that express TRPV1 were selected for in vitro screening of LNPs to determine...
Source: The Journal of Pain - May 1, 2021 Category: Materials Science Authors: Purva Khare, Kandarp Dave, Jane Hartung, Michael Gold, Devika Manickam Source Type: research

Development of an activated microglia cell line model for screening lipid nanoparticle formulations of BDNF siRNA for neuropathic pain therapy
Purpose Brain-derived neurotrophic factor (BDNF) released from activated spinal microglia via the ATP-P2  × 4R-BDNF signaling pathway plays a central role in initiating pain hypersensitivity in neuropathic pain. Therefore, knockdown of BDNF expression in microglia using molecules like siRNA can be a promising strategy for neuropathic pain therapy. Our lab is developing lipidoid nanoparticles (LNP) for the delivery of BDNF siRNA (siBDNF) for treating neuropathic pain. We characterized the Spontaneously Immortalized Microglia-A9 (SIM-A9) cell line and confirmed the expression of Iba1, P2 × 4R, and BDNF under restin...
Source: The Journal of Pain - May 1, 2021 Category: Materials Science Authors: Kandarp Dave, Lalah Ali, Devika S Manickam Source Type: research

MiR-502 Suppresses TNF- < em > α < /em > -Induced Nucleus Pulposus Cell Apoptosis by Targeting TARF2
This study is aimed at investigating the role of microRNAs (miRNAs) in regulating human nucleus pulposus (NP) cell injury induced by tumor necrosis factor- (TNF-) α in IVDD. In this study, we induced NP cells with 20 ng/mL TNF-α in vitro, which promoted the obvious apoptosis of NP cells and the activation of nuclear transcription factor (NF)-κB. In contrast, using the specific NF-κB inhibitor BAY 11-7082 to treat cells greatly impaired the activation of NF-κB and increased the sensitivity of NP cells to TNF-α-induced apoptosis. Moreover, both TNF-α and BAY 11-7082 treatments were associated with marked miRNA dysregu...
Source: Biomed Res - April 19, 2021 Category: Research Authors: Zhao Guo Wen-Shan Gao Yun-Fei Wang Fei Gao Wei Wang Wen-Yuan Ding Source Type: research

Givosiran: A Review in Acute Hepatic Porphyria
AbstractGivosiran (Givlaari®) is an δ-aminolevulinic acid synthase 1 (ALAS1)-directed small interfering RNA (siRNA) approved for the treatment of acute hepatic porphyria (AHP). In the phase 3 ENVISION trial, givosiran significantly reduced the annualized rate of composite porphyria attacks (i.e. attacks requiring hospitalization, urg ent healthcare visit or intravenous hemin administration at home) compared with placebo in patients with recurrent acute intermittent porphyria (the most common type of AHP) attacks. Givosiran also improved several other outcomes, including hemin use and pain (the cardinal symptom of AHP). W...
Source: Drugs - April 19, 2021 Category: Drugs & Pharmacology Source Type: research

Intrathecal Injection of GRIP-siRNA Reduces Postoperative Synaptic Abundance of Kainate Receptor GluK2 Subunits in Rat Dorsal Horns and Pain Hypersensitivity
Neurochem Res. 2021 Apr 13. doi: 10.1007/s11064-021-03323-z. Online ahead of print.ABSTRACTThe mechanisms underlying postoperative pain differ from the inflammatory or neuropathic pain. Previous studies have demonstrated that intrathecal α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) -kainate (KA) receptor antagonist inhibits the guarding pain behavior and mechanical hyperalgesia, indicating a critical role of spinal KA receptors in postoperative pain hypersensitivity. However, how the functional regulations of spinal KA receptor subunits are involved in the postoperative pain hypersensitivity remains elusive. Th...
Source: Neurochemical Research - April 13, 2021 Category: Neuroscience Authors: Ruijuan Guo Huili Li Rong Shi Yun Wang Source Type: research

Novel treatment options for acute hepatic porphyrias
Purpose of review Acute hepatic porphyrias (AHP) are a group of rare diseases that are characterized by episodic acute neurovisceral pain episodes caused by abnormal accumulation of the neurotoxic porphyrin precursor delta-aminolevulinic acid (ALA). Patient with frequent recurrent acute attacks have been difficult to treat and these patients sometimes require liver transplantation. Recent developments in small interfering RNA (siRNA)-based therapy led to the development of an effective prophylactic treatment for patients with frequent recurrent attacks. This review will describe treatment options for AHP and highlight ...
Source: Current Opinion in Gastroenterology - April 9, 2021 Category: Gastroenterology Tags: LIVER: Edited by Don C. Rockey Source Type: research

TRAF6 Contributes to CFA-Induced Spinal Microglial Activation and Chronic Inflammatory Pain in Mice
In this study, we investigated the role and mechanism of TRAF6 in complete Freund's adjuvant (CFA)-evoked chronic inflammatory hypersensitivity and the effect of docosahexaenoic acid (DHA) on TRAF6 expression and inflammatory pain. We found that TRAF6 was dominantly increased in microglia at the spinal level after intraplantar injection of CFA. Intrathecal TRAF6 siRNA alleviated CFA-triggered allodynia and reversed the upregulation of IBA-1 (microglia marker). In addition, intrathecal administration of DHA inhibited CFA-induced upregulation of TRAF6 and IBA-1 in the spinal cord and attenuated CFA-evoked mechanical allodyni...
Source: Cellular and Molecular Neurobiology - March 11, 2021 Category: Cytology Authors: Ying Lu De-Li Cao Ling-Jie Ma Yong-Jing Gao Source Type: research

Duloxetine suppresses BMP-4-induced release of osteoprotegerin via inhibition of the SMAD signaling pathway in osteoblasts
Biochem Cell Biol. 2021 Mar 1. doi: 10.1139/bcb-2020-0347. Online ahead of print.ABSTRACTDuloxetine, a selective serotonin-norepinephrine reuptake inhibitor, is currently recommended to use in the treatment of chronic painful disorders such as fibromyalgia, chronic musculoskeletal pain and diabetic peripheral neuropathy. We previously demonstrated that bone morphogenetic protein-4 (BMP-4) stimulates osteoprotegerin (OPG) production in osteoblast-like MC3T3-E1 cells, and that p70 S6 kinase positively regulates the OPG synthesis. The present study is aimed to investigate the effect of duloxetine on BMP-4-stimulated OPG synth...
Source: Biochemistry and Cell Biology - March 1, 2021 Category: Biochemistry Authors: Junko Tachi Takashi Onuma Shinobu Yamaguchi Woo Kim Tomoyuki Hioki Rie Matsushima-Nishiwaki Kumiko Tanabe Haruhiko Tokuda Osamu Kozawa Hiroki Iida Source Type: research