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Condition: Chronic Pain

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Total 159 results found since Jan 2013.

Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis
This study was funded by the Academy of Finland and by Tekes: Finnish Funding Agency for Innovation. The authors have no conflict of interest to declare.
Source: Human Reproduction - February 15, 2018 Category: Reproduction Medicine Source Type: research

Chronic stress-associated visceral hyperalgesia correlates with severity of intestinal barrier dysfunction
In humans, chronic psychological stress is associated with increased intestinal paracellular permeability and visceral hyperalgesia, which is recapitulated in the chronic intermittent water avoidance stress (WAS) rat model. However, it is unknown whether enhanced visceral pain and permeability are intrinsically linked and correlate. Treatment of rats with lubiprostone during WAS significantly reduced WAS-induced changes in intestinal epithelial paracellular permeability and visceral hyperalgesia in a subpopulation of rats. Lubiprostone also prevented WAS-induced decreases in the epithelial tight junction protein, occludin ...
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Endometriotic inflammatory microenvironment induced by macrophages can be targeted by niclosamide.
Abstract Endometriosis causes severe chronic pelvic pain and infertility. We have recently reported that niclosamide treatment reduces growth and progression of endometriosis-like lesions and inflammatory signaling (NFĸB and STAT3) in a mouse model. In the present study, we examined further inhibitory mechanisms by which niclosamide affects endometriotic lesions using an endometriotic epithelial cell line, 12Z, and macrophages differentiated from a monocytic THP-1 cell line. Niclosamide dose dependently reduced 12Z viability, reduced STAT3 and NFĸB activity, and increased both cleaved caspase-3 and cleaved PARP....
Source: Biology of Reproduction - October 16, 2018 Category: Reproduction Medicine Authors: Sekulovski N, Whorton AE, Shi M, Ii JAM, Hayashi K Tags: Biol Reprod Source Type: research

A novel synthetic small molecule DMFO targets Nrf2 in modulating proinflammatory/antioxidant mediators to ameliorate inflammation.
We report the synthesis and anti-inflammatory/antioxidant activity of a novel indanedione derivative DMFO. DMFO scavenged reactive oxygen species (ROS) in in-vitro radical scavenging assays and in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. In acute models of inflammation (carrageenan-induced inflammation in rat paw and air pouch), DMFO effectively reduced paw oedema and leucocyte infiltration with an activity comparable to diclofenac. DMFO stabilised mast cells (MCs) in in-vitro A23187 and compound 48/80-induced assays. Additionally, DMFO stabilised MCs in an antigen (ovalbumin)-induced MC degranulation mod...
Source: Free Radical Research - November 15, 2018 Category: Research Tags: Free Radic Res Source Type: research

RE1-silencing transcription factor controls the acute-to-chronic neuropathic pain transition and Chrm2 receptor gene expression in primary sensory neurons Neurobiology
Neuropathic pain is associated with persistent changes in gene expression in primary sensory neurons, but the underlying epigenetic mechanisms that cause these changes remain unclear. The muscarinic cholinergic receptors (mAChRs), particularly the M2 subtype (encoded by the cholinergic receptor muscarinic 2 (Chrm2) gene), are critically involved in the regulation of spinal nociceptive transmission. However, little is known about how Chrm2 expression is transcriptionally regulated. Here we show that nerve injury persistently increased the expression of RE1-silencing transcription factor (REST, also known as neuron-restricti...
Source: Journal of Biological Chemistry - December 7, 2018 Category: Chemistry Authors: Jixiang Zhang, Shao-Rui Chen, Hong Chen, Hui-Lin Pan Tags: Molecular Bases of Disease Source Type: research

FOXP1 enhances fibrosis via activating Wnt/ β-catenin signaling pathway in endometriosis.
In this study we used endometrial and endometriotic stromal cells isolated from patients, and employed siRNA to knockdown Forkhead box protein P1 (FOXP1) to investigate the effect of FOXP1 on collagen contraction, cell proliferation and mitigation. Western blot and quantitative PCR were applied for analysis of protein and mRNA levels, respectively. Compared to control stromal cells, endometriotic stromal cells from patients exhibited higher levels of FOXP1 expression and Wnt-related β-catenin acetylation. FOXP1 knockdown decreased not only Wnt signaling, but also the expression of fibrotic marker genes, including connecti...
Source: American Journal of Translational Research - January 24, 2019 Category: Research Tags: Am J Transl Res Source Type: research

Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury
In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal respons...
Source: Pain - January 24, 2019 Category: Anesthesiology Tags: Research Paper 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

Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology 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

EPHA3 enhances macrophage autophagy and apoptosis by disrupting the mTOR signaling pathway in mice with endometriosis.
CONCLUSION: Altogether, EPHA3 could potentially promote the autophagy and apoptosis of macrophages in endometriosis via inhibition of the mTOR signaling pathway, highlighting the potential of EPHA3 as the target to treat endometriosis. PMID: 31262977 [PubMed - as supplied by publisher]
Source: Bioscience Reports - June 30, 2019 Category: Biomedical Science Authors: Xu H, Gao Y, Shu Y, Wang Y, Shi Q Tags: Biosci Rep Source Type: research

Nrf2/HO-1 signaling pathway participated in the protection of hydrogen sulfide on neuropathic pain in rats.
Abstract Neuropathic pain is evoked by aberrant sensory processing in the peripheral or central nervous system, which is characterized by persistent pain, tactile allodynia, or hyperalgesia. Neuroinflammation is associated with the initiation and maintenance of persistent pain in both the peripheral and central nervous systems. Hydrogen sulfide plays important regulatory roles in different physiological and pathological conditions. Therefore, we investigated the effect of hydrogen sulfide on allodynia, hyperalgesia and cytokine release in rats with neuropathic pain and the related regulatory mechanism. Neuropathic...
Source: International Immunopharmacology - July 16, 2019 Category: Allergy & Immunology Authors: Chen H, Xie K, Chen Y, Wang Y, Wang Y, Lian N, Zhang K, Yu Y Tags: Int Immunopharmacol Source Type: research

The CUL3/neddylation inhibitor MLN4924 reduces ethanol-induced locomotor sensitization and inflammatory pain allodynia in mice.
Abstract Heterologous sensitization of adenylyl cyclase (AC) is defined by an enhanced cAMP response following persistent activation of Gαi/o-coupled receptors. This phenomenon was first observed in cellular models, and later reported in animal models of inflammatory pain or following chronic exposure to drugs of abuse including opioids and cocaine. Recently, we used genome-wide siRNA screening to identify Cullin3 signaling as a mediator of AC sensitization in cellular models. We also showed that pharmacological inhibition of Cullin3 with the neddylation inhibitor, MLN4924, abolished heterologous sensitization of...
Source: Behavioural Brain Research - December 3, 2020 Category: Neurology Authors: Ding Z, Knipp GT, van Rijn RM, Chester JA, Watts VJ Tags: Behav Brain Res Source Type: research

A thermosensitive, reactive oxygen species-responsive, MR409-encapsulated hydrogel ameliorates disc degeneration in rats by inhibiting the secretory autophagy pathway
Conclusion: Secretory autophagy and associated IL-1β secretion contribute to the pathogenesis of disc degeneration, and MR409 can effectively inhibit this pathway. The ROS-responsive thermosensitive hydrogel encapsulated with MR409 is a potentially efficacious treatment for disc degeneration.
Source: Theranostics - January 15, 2021 Category: Molecular Biology Authors: Qiangqiang Zheng, Haotian Shen, Zongrui Tong, Linxiang Cheng, Yuzi Xu, Zhiyun Feng, Shiyao Liao, Xiaojian Hu, Zongyou Pan, Zhengwei Mao, Yue Wang Tags: Research Paper Source Type: research