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Condition: Pain

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Total 374 results found since Jan 2013.

Dorsal root ganglia coactivator-associated arginine methyltransferase 1 contributes to peripheral nerve injury-induced pain hypersensitivities
We report here that peripheral nerve injury induced the upregulation of the mRNA and protein expression of CARM1 in the injured DRG, and blocking its expression through small interfering RNA (siRNA) in the injured DRG attenuated the development and maintenance of neuropathic pain. Furthermore, pharmacological inhibition of CARM1 mitigated peripheral nerve injury-induced mechanical allodynia and thermal hyperalgesia. Given that CARM1 inhibition or knockdown attenuated the induction and maintenance of neuropathic pain after peripheral nerve injury, our findings suggest that CARM1 may serve as a promising therapeutic target f...
Source: Neuroscience - November 2, 2018 Category: Neuroscience 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

Efficiency of dual siRNA-mediated gene therapy for intervertebral disc degeneration (IVDD)
One of the common causes of low back pain is intervertebral disc degeneration. The pathophysiology of disc degeneration involves apoptosis of nucleus pulposes cells and degradation of extra cellular matrix (ECM). Caspase 3 plays a central role in apoptosis and the ADAMTS5 (A Disintegrin and Metalloproteinase with Thrombospondin motifs 5) gene plays a critical role in ECM degradation. Hence, we hypothesized that if one can silence these two genes, both apoptosis and ECM degradation can be prevented, thereby preventing the progression and even reverse disc degeneration.
Source: The Spine Journal - November 12, 2018 Category: Orthopaedics Authors: Rajkiran Reddy Banala, Satish Kumar Vemuri, Ghulam Hassan Dar, Vijayanand Palanisamy, Murahari P, Surekha MV, Gurava Reddy AV, Madhusudhana Rao Nalam, Subbaiah GPV Tags: Basic Science 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

Gelsemine and koumine, principal active ingredients of Gelsemium, exhibit mechanical antiallodynia via spinal glycine receptor activation-induced allopregnanolone biosynthesis.
Abstract Gelsemine, the principal active alkaloid from Gelsemium sempervirens Ait., and koumine, the most dominant alkaloids from Gelsemium elegans Benth., produced antinociception in a variety of rodent models of painful hypersensitivity. The present study explored the molecular mechanisms underlying gelsemine- and koumine-induced mechanical antiallodynia in neuropathic pain. The radioligand binding and displacement assays indicated that gelsemine and koumine, like glycine, were reversible and orthosteric agonists of glycine receptors with full efficacy and probably acted on same binding site as the glycine recep...
Source: Biochemical Pharmacology - January 19, 2019 Category: Drugs & Pharmacology Authors: Shoaib RM, Zhang JY, Mao XF, Wang YX Tags: Biochem Pharmacol 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

Ketamine inhibits colorectal cancer cells malignant potential via blockage of NMDA receptor.
Abstract Ketamine, a common N-methyl-d-aspartate receptor (NMDAR) antagonist, is an option for cancer pain treatment in clinical practice. Ketamine has been shown to have the capacity to attenuate cancer cells malignancy. However, the underlying mechanism remains elusive. In the present study, we reported that ketamine inhibited the malignant potential of colorectal cancer cells and investigated the possible mechanisms involved. Ketamine suppressed the expression of VEGF, HIF-1α, p-AKT, p-ERK, and p-CaMK II, and reduced intracellular Ca2+ level in a concentration dependent manner (1, 5, 10 μg/ml). Furthermore,...
Source: Experimental and Molecular Pathology - February 25, 2019 Category: Pathology Authors: Duan W, Hu J, Liu Y Tags: Exp Mol Pathol Source Type: research

Why Do Birds Flock? A Role for Opioids in the Reinforcement of Gregarious Social Interactions
Conclusion We propose that studies of songbirds reveal a novel network model for the integration of positive and negative reinforcement processes in non-sexual affiliative social behavior. Most studies on affiliative behavior focus on the positive affective state induced by social contact that rewards individuals interacting together. However, this review highlights that in social animals, affiliative contact is also reinforced because it reduces a negative affective state caused by social exclusion or isolation, thus creating a complementary system (i.e., positive reinforcement from affiliative interactions and negative ...
Source: Frontiers in Physiology - April 11, 2019 Category: Physiology 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

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

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

Dihydroartemisinin derivative DC32 inhibits inflammatory response in osteoarthritic synovium through regulating Nrf2/NF- κB pathway.
In conclusion, DC32 inhibited the inflammatory response in osteoarthritic synovium through regulating Nrf2/NF-κB pathway and attenuated OA. In this way, DC32 may be a potential agent in the treatment of OA. PMID: 31228817 [PubMed - as supplied by publisher]
Source: International Immunopharmacology - June 18, 2019 Category: Allergy & Immunology Authors: Li YN, Fan ML, Liu HQ, Ma B, Dai WL, Yu BY, Liu JH Tags: Int Immunopharmacol Source Type: research