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Condition: Chronic Pain

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Total 159 results found since Jan 2013.

JAB1 is Involved in Neuropathic Pain by Regulating JNK and NF-κB Activation After Chronic Constriction Injury.
This study aimed to investigate the possible involvement of JAB1. Here, employing a neuropathic pain model induced by chronic constriction injury (CCI) on rats, we reported the role of JAB1 in the maintenance of neuropathic pain. By western blot, we found that CCI markedly up-regulated JAB1 expression in the dorsal root ganglion (DRG) and spinal cord. Immunofluorescent assay demonstrated that JAB1 was extensively localized in IB4-, CGRP- and NF200-positive neurons in the injured L5 DRG, and mainly co-localized with NeuN in spinal cord. In addition, we showed that CCI induced phosphorylation of p65 and JNK in vivo. Intrathe...
Source: Neurochemical Research - December 23, 2015 Category: Neuroscience Authors: Chen Y, Chen X, Yu J, Xu X, Wei X, Gu X, Liu C, Zhang D, Xu Z Tags: Neurochem Res Source Type: research

Pain: FKBP51 inhibition reduces chronic pain
Nature Reviews Drug Discovery 15, 234 (2016). doi:10.1038/nrd.2016.55 Author: Sarah Crunkhorn Polymorphisms in the gene encoding FK506 binding protein 51 (FKBP51) — a regulator of steroid hormone signalling — influence the severity of musculoskeletal pain symptoms after trauma. Here, using Fkbp51-knockout mice and siRNA-induced silencing of Fkbp51 in the mouse spinal cord, Maiarù et
Source: Nature Reviews Drug Discovery - March 31, 2016 Category: Drugs & Pharmacology Authors: Sarah Crunkhorn Tags: Research Highlight Source Type: research

Opioid Receptor Expression in Neuropathic Pain Neurobiology
In this study, we determined the role of G9a in diminished MOR expression and opioid analgesic effects in animal models of neuropathic pain. We found that nerve injury in rats induced a long-lasting reduction in the expression level of MORs in the DRG but not in the spinal cord. Nerve injury consistently increased the enrichment of the G9a product histone 3 at lysine 9 dimethylation in the promoter of Oprm1 in the DRG. G9a inhibition or siRNA knockdown fully reversed MOR expression in the injured DRG and potentiated the morphine effect on pain hypersensitivity induced by nerve injury. In mice lacking Ehmt2 in DRG neurons, ...
Source: Journal of Biological Chemistry - April 14, 2016 Category: Chemistry Authors: Zhang, Y., Chen, S.-R., Laumet, G., Chen, H., Pan, H.-L. Tags: Molecular Bases of Disease Source Type: research

Role of Nectin-1/c-Src Signaling in the Analgesic Effect of GDNF on a Rat Model of Chronic Constrictive Injury
In this study, we aimed to examine whether the adhesion protein nectin-1 and its downstream protein c-Src are involved in neuropathic pain. We found that nectin-1 was expressed in the superficial dorsal horn of the spinal cord and that it was increased after chronic constrictive injury (CCI). Intrathecal administration of nectin-1 siRNA attenuated neuropathic pain induced by CCI via interference of the expression of nectin-1. Furthermore, we found that GDNF can downregulate the phosphorylation level of nectin-1-associated c-Src without changing the expression level of nectin-1. In summary, these data suggest that nectin-1 ...
Source: Journal of Molecular Neuroscience - July 8, 2016 Category: Neuroscience 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

More on Epigenetics and Pain
Great Research Tools!OurMarkers and i-FectTM Transection Kit are used to studyEpigenetics and pain. Here ' s yet another example:M. Leinders, b, N. Üçeyler, R.A. Pritchard, C. Sommer, L.S. Sorkin. Increased miR-132-3p expression is associated with chronic neuropathic pain. Experimental Neurology. Volume 283, Part A, September 2016, Pages 276 –286...The inhibitor and mimetic were administered to awake rats via the it catheters. Prior to injection, active or mismatch inhibitors were mixed with (1:5 w/v) i-Fect™ in vivo transfection reagent(Neuromics, Edina, USA) to final doses of 5, 2 and 1 μg in 10 μl...Fi...
Source: Neuromics - August 19, 2016 Category: Neuroscience Tags: chronic pain iFect miRNA siRNA delivery in-vivo Source Type: news

Delivering miRNA in vivo
More Transfection Success!Great Research Tools!Our i-FectTM  Transfection Kit is used to studyEpigenetics and pain. Here ' s yet another example:M. Leinders, b, N. Üçeyler, R.A. Pritchard, C. Sommer, L.S. Sorkin. Increased miR-132-3p expression is associated with chronic neuropathic pain. Experimental Neurology. Volume 283, Part A, September 2016, Pages 276 –286...The inhibitor and mimetic were administered to awake rats via the it catheters. Prior to injection, active or mismatch inhibitors were mixed with (1:5 w/v) i-Fect™ in vivo transfection reagent(Neuromics, Edina, USA) to final doses of 5, 2 and...
Source: siRNA and DsiRNA Transfection Efficiency - August 19, 2016 Category: Neuroscience Tags: iFect miRNA Delivery Methods Source Type: news

More iFect in-vivo
The parade of publications continues to grow.Here researchers use our i-FectTM Transfection Kit for delivering sh-IRF3in vivo:Rui Li, Li-guo Wang, Qi Wang, Zhi-hua Li, Ya-li Ma, Qing-Duo Guo. Silencing of IRF3 alleviates chronic neuropathic pain following chronic constriction injury. doi.org/10.1016/j.biopha.2017.01.085... The oligonucleotides for sh-IRF3 were: 5 ′-CACCGCGTCTAGGCTGGTGGTTATTCGAAAATAACCACCAGCCTAGACGC-3′ −3′. Then, 10 μg sh-IRF3 dissolved in 30 μl i-Fect transfection reagent (Neuromics, Edina, MN, USA) was administered intrathecally once daily for 7...Fig. Down-regulation of IRF3 attenuated mechanic...
Source: siRNA and DsiRNA Transfection Efficiency - January 30, 2017 Category: Neuroscience Tags: iFect IFR3 inflammatory pain Source Type: news

Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice.
Abstract Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared...
Source: Experimental Neurology - February 4, 2017 Category: Neurology Authors: Lin YT, Liu HL, Day YJ, Chang CC, Hsu PH, Chen JC Tags: Exp Neurol Source Type: research

Recent Advances in the Development of T ‐type Calcium Channel Blockers for Pain Intervention
Abstract Cav3.2 T‐type calcium channels are important regulators of pain signals in afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore it stands to reason that inhibiting T‐type calcium channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief. This is supported by early pharmacological studies with T‐type channel blockers such as ethosuximide, and by analgesic effects of siRNA depletion of Cav3.2 channels. In the past five years, considerable effort has been applied towards identifying novel classes of T‐type calci...
Source: British Journal of Pharmacology - June 13, 2017 Category: Drugs & Pharmacology Authors: Terrance P Snutch, Gerald W Zamponi Tags: REVIEW ARTICLE THEMED ISSUE Source Type: research

Silencing of FKBP51 alleviates the mechanical pain threshold, inhibits DRG inflammatory factors and pain mediators through the NF-kappaB signaling pathway.
Abstract Neuropathic pain is chronic pain caused by lesions or diseases of the somatosensory system, currently available analgesics provide only temporal relief. The precise role of FK506 binding protein 51 (FKBP51) in neuropathic pain induced by chronic constriction injury (CCI) is not clear. The purpose of the present study was to investigate the effects and possible mechanisms of FKBP51 in neuropathic pain in the rat model of CCI. Our results showed that FKBP51 was obviously upregulated in a time-dependent manner in the dorsal root ganglion (DRG) in CCI rats. Additionally, silencing of FKBP51 remarkably attenua...
Source: Gene - June 16, 2017 Category: Genetics & Stem Cells Authors: Yu HM, Wang Q, Sun WB Tags: Gene Source Type: research

Vimentin Promotes Astrocyte Activation After Chronic Constriction Injury
In this study, the role of vimentin in chronic constriction injury (CCI) was investigated. Western blot revealed increased protein level of vimentin following CCI, peaking at 7  days. Double immunofluorescent staining showed that vimentin was mostly co-localized with astrocytes, not with neurons or microglia. In vitro, sensory neuronal injury stimulated astrocytes to produce more pro-inflammation cytokines, p-ERK (phosphorylated extracellular signal-regulated protein kina se), and vimentin. However, vimentin knockdown by siRNA (small interfering RNA) reversed the upregulation of p-ERK and vimentin expression and reduced t...
Source: Journal of Molecular Neuroscience - August 8, 2017 Category: Neuroscience Source Type: research

Downregulations of TRPM8 expression and membrane trafficking in dorsal root ganglion mediate the attenuation of cold hyperalgesia in CCI rats induced by GFR α3 knockdown.
CONCLUSION: Our results demonstrate that GFRα3 knockdown specially inhibits cold hyperalgesia following CCI via decreasing the expression level and plasma membrane trafficking of TRPM8 in DRG. GFRα3 and its downstream mediator, TRPM8, represent a new analgesia axis which can be further exploited in sensitized cold reflex under the condition of chronic pain. PMID: 28867384 [PubMed - as supplied by publisher]
Source: Brain Research Bulletin - August 31, 2017 Category: Neurology Authors: Su L, Shu R, Song C, Yu Y, Wang G, Li Y, Liu C Tags: Brain Res Bull Source Type: research

Fascin-1 Contributes to Neuropathic Pain by Promoting Inflammation in Rat Spinal Cord.
Abstract Neuropathic pain is a complicated clinical syndrome caused by heterogeneous etiology. Despite the fact that the underlying mechanisms remain elusive, it is well accepted that neuroinflammation plays a critical role in the development of neuropathic pain. Fascin-1, an actin-bundling protein, has been proved to be involved in the processing of diverse biological events including cellular development, immunity, and tumor invasion etc. Recent studies have shown that Fascin-1 participates in antigen presentation and the regulation of pro-inflammatory agents. However, whether Fascin-1 is involved in neuropathic...
Source: Neurochemical Research - October 19, 2017 Category: Neuroscience Authors: Wang B, Fan B, Dai Q, Xu X, Jiang P, Zhu L, Dai H, Yao Z, Xu Z, Liu X Tags: Neurochem Res Source Type: research

MicroRNA-146a-5p attenuates visceral hypersensitivity through targeting chemokine CCL8 in the spinal cord in a mouse model of colitis.
In this study, we aimed to explore the potential role of miR-146a-5p (the mature form of miR-146a) in a mouse model of colitis induced by intracolonic injection of trinitrobenzene sulfonic acid (TNBS). We found that induction of colitis resulted in visceral hyperalgesia manifested by a decreased pain threshold to colorectal distension and upregulation of miR-146a-5p expression in the lumbosacral spinal cord. In situ hybridization and immunohistochemistry results showed that miR-146a-5p was colocalized with neuronal marker NeuN, but not with astrocytic marker GFAP or microglial marker IBA-1. Dual-luciferase reporter assay s...
Source: Brain Research Bulletin - March 14, 2018 Category: Neurology Authors: Lu Y, Cao DL, Zhao LX, Han Y, Zhang YL Tags: Brain Res Bull Source Type: research