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https://www.readbyqxmd.com/read/29017971/induction-of-suppressor-of-cytokine-signaling-3-via-hsf-1-hsp70-tlr4-axis-attenuates-neuroinflammation-and-ameliorates-postoperative-pain
#1
Yi-Xin Fan, Cheng Qian, Bingqian Liu, Chaoyu Wang, Haijiao Liu, Xiuxiu Pan, Peng Teng, Liang Hu, Guangqin Zhang, Yuan Han, Mi Yang, Xue-Feng Wu, Wen-Tao Liu
Postoperative pain is a common form of acute pain that, if not managed effectively, can become chronic pain. Evidence has shown that glia, especially microglia, mediate neuroinflammation, which plays a vital role in pain sensitization. Moreover, toll-like receptor 4 (TLR4), the tumor necrosis factor receptor (TNF-R), the interleukin-1 receptor (IL-1R), and the interleukin-6 receptor (IL-6R) have been considered key components in central pain sensitization and neuroinflammation. Therefore, we hypothesized that activation of the body's endogenous "immune brakes" will inhibit these receptors and achieve inflammation tolerance as well as relieve postoperative pain...
October 7, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28987324/toll-like-receptors-and-their-role-in-persistent-pain
#2
REVIEW
Michael J Lacagnina, Linda R Watkins, Peter M Grace
One of the fundamental mechanisms whereby the innate immune system coordinates inflammatory signal transduction is through Toll-like receptors (TLRs), which function to protect and defend the host organism by initiating inflammatory signaling cascades in response to tissue damage or injury. TLRs are positioned at the neuroimmune interface, and accumulating evidence suggests that the inflammatory consequences of TLR activation on glia (including microglia and astrocytes), sensory neurons, and other cell types can influence nociceptive processing and lead to states of exaggerated and unresolved pain...
October 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28986553/brain-atrophy-in-the-visual-cortex-and-thalamus-induced-by-severe-stress-in-animal-model
#3
Takanobu Yoshii, Naoya Oishi, Kazuya Ikoma, Isao Nishimura, Yuki Sakai, Kenichi Matsuda, Shunji Yamada, Masaki Tanaka, Mitsuhiro Kawata, Jin Narumoto, Kenji Fukui
Psychological stress induces many diseases including post-traumatic stress disorder (PTSD); however, the causal relationship between stress and brain atrophy has not been clarified. Applying single-prolonged stress (SPS) to explore the global effect of severe stress, we performed brain magnetic resonance imaging (MRI) acquisition and Voxel-based morphometry (VBM). Significant atrophy was detected in the bilateral thalamus and right visual cortex. Fluorescent immunohistochemistry for Iba-1 as the marker of activated microglia indicates regional microglial activation as stress-reaction in these atrophic areas...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28974234/agonists-for-g-protein-coupled-receptor-84-gpr84-alter-cellular-morphology-and-motility-but-do-not-induce-pro-inflammatory-responses-in-microglia
#4
Li Wei, Kyohei Tokizane, Hiroyuki Konishi, Hua-Rong Yu, Hiroshi Kiyama
BACKGROUND: Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood...
October 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28973941/granulocyte-colony-stimulating-factor-g-csf-signaling-in-spinal-microglia-drives-visceral-sensitization-following-colitis
#5
Lilian Basso, Tamia K Lapointe, Mircea Iftinca, Candace Marsters, Morley D Hollenberg, Deborah M Kurrasch, Christophe Altier
Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28954391/neuron-glia-crosstalk-and-neuropathic-pain-involvement-in-the-modulation-of-motor-activity-in-the-orofacial-region
#6
REVIEW
Mohammad Zakir Hossain, Shumpei Unno, Hiroshi Ando, Yuji Masuda, Junichi Kitagawa
Neuropathic orofacial pain (NOP) is a debilitating condition. Although the pathophysiology remains unclear, accumulating evidence suggests the involvement of multiple mechanisms in the development of neuropathic pain. Recently, glial cells have been shown to play a key pathogenetic role. Nerve injury leads to an immune response near the site of injury. Satellite glial cells are activated in the peripheral ganglia. Various neural and immune mediators, released at the central terminals of primary afferents, lead to the sensitization of postsynaptic neurons and the activation of glia...
September 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28952414/src-family-kinases-activation-in-spinal-microglia-contributes-to-central-sensitization-and-chronic-pain-after-lumbar-disc-herniation
#7
Yangliang Huang, Yongyong Li, Xiongxiong Zhong, Yuming Hu, Pan Liu, Yuanshu Zhao, Zhen Deng, Xianguo Liu, Shaoyu Liu, Yi Zhong
Background Lumbar disc herniation is a major cause of radicular pain, but the underlying mechanisms remain largely unknown. Spinal activation of src-family kinases are involved in the development of chronic pain from nerve injury, inflammation, and cancer. In the present study, the role of src-family kinases activation in lumbar disc herniation-induced radicular pain was investigated. Results Lumbar disc herniation was induced by implantation of autologous nucleus pulposus, harvest from tail, in lumbar 4/5 spinal nerve roots of rat...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28947688/-pathophysiology-and-treatment-of-orofacial-pain
#8
Masamichi Shinoda, Noboru Noma
"Pain" is one of body defense mechanisms and crucial for the life support. However, orofacial pain such as myofascial pain syndrome, burning mouth syndrome and trigeminal neuralgia plays no part in body defense mechanisms and requires therapeutic intervention. Recent studies have indicated that plastic changes in the activities of trigeminal neurons, satellite glial cells in trigeminal ganglion, secondary neurons, microglia and astrocytes in trigeminal spinal subnucleus following orofacial inflammation and trigeminal nerve injury are responsible for orofacial pain mechanisms...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28943285/ethanol-differentially-modulates-p2x4-and-p2x7-receptor-activity-and-function-in-bv2-microglial-cells
#9
Liana Asatryan, Olga Ostrovskaya, Dustin Lieu, Daryl L Davies
Neuroinflammation is one of the mechanisms leading to neurodegenerative brain damage induced by chronic alcohol (ethanol) exposure. Microglia play a major role in the development of innate immune responses to environmental injuries including ethanol. Adenosine 5″-triphosphate (ATP)-activated purinergic P2X receptor (P2XR) subtypes, P2X4Rs and P2X7Rs, are endogenously expressed in microglia and can modulate their activity. These 2 P2XR subtypes differ pharmacologically and functionally: 1) P2X4Rs are activated at lower (≤0...
September 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28928988/the-effect-of-glucocorticoid-and-glucocorticoid-receptor-interactions-on-brain-spinal-cord-and-glial-cell-plasticity
#10
REVIEW
Kathryn M Madalena, Jessica K Lerch
Stress, injury, and disease trigger glucocorticoid (GC) elevation. Elevated GCs bind to the ubiquitously expressed glucocorticoid receptor (GR). While GRs are in every cell in the nervous system, the expression level varies, suggesting that diverse cell types react differently to GR activation. Stress/GCs induce structural plasticity in neurons, Schwann cells, microglia, oligodendrocytes, and astrocytes as well as affect neurotransmission by changing the release and reuptake of glutamate. While general nervous system plasticity is essential for adaptation and learning and memory, stress-induced plasticity is often maladaptive and contributes to neuropsychiatric disorders and neuropathic pain...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28928366/fibromyalgia-and-microglial-tnf-%C3%AE-translational-research-using-human-blood-induced-microglia-like-cells
#11
Masahiro Ohgidani, Takahiro A Kato, Masako Hosoi, Makoto Tsuda, Kohei Hayakawa, Chie Hayaki, Rie Iwaki, Noriaki Sagata, Ryota Hashimoto, Kazuhide Inoue, Nobuyuki Sudo, Shigenobu Kanba
Fibromyalgia is a refractory disease characterized by chronic intractable pain and psychological suffering, the cause of which has not yet been elucidated due to its complex pathology. Activation of immune cells in the brain called microglia has attracted attention as a potential underlying pathological mechanism in chronic pain. Until recently, however, technological and ethical considerations have limited the ability to conduct research using human microglia. To overcome this limitation, we have recently developed a technique to create human-induced microglia-like (iMG) cells from human peripheral blood monocytes...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924009/site-specific-regulation-of-p2x7-receptor-function-in-microglia-gates-morphine-analgesic-tolerance
#12
Heather Leduc-Pessah, Nicholas L Weilinger, Churmy Y Fan, Nicole E Burma, Roger J Thompson, Tuan Trang
Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca(2+) responses in resident spinal microglia acutely isolated from morphine tolerant rats...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28899427/activation-of-dorsal-horn-cannabinoid-cb2-receptor-suppresses-the-expression-of-p2y12-and-p2y13-receptors-in-neuropathic-pain-rats
#13
Juan Niu, Dujuan Huang, Rui Zhou, MingXia Yue, Tao Xu, Junna Yang, Li He, Hong Tian, XiaoHong Liu, Junwei Zeng
BACKGROUND: More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. METHODS: Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain...
September 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28886007/microglia-emerge-as-central-players-in-brain-disease
#14
REVIEW
Michael W Salter, Beth Stevens
There has been an explosion of new findings recently giving us insights into the involvement of microglia in central nervous system (CNS) disorders. A host of new molecular tools and mouse models of disease are increasingly implicating this enigmatic type of nervous system cell as a key player in conditions ranging from neurodevelopmental disorders such as autism to neurodegenerative disorders such as Alzheimer's disease and chronic pain. Contemporaneously, diverse roles are emerging for microglia in the healthy brain, from sculpting developing neuronal circuits to guiding learning-associated plasticity...
September 8, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28881783/effect-and-mechanism-of-inhibition-of-pi3k-akt-mtor-signal-pathway-on-chronic-neuropathic-pain-and-spinal-microglia-in-a-rat-model-of-chronic-constriction-injury
#15
Jian-Rong Guo, Huan Wang, Xiao-Ju Jin, Dong-Lin Jia, Xun Zhou, Qiang Tao
OBJECTIVE: To explore the effects of inhibition of PI3K/Akt/mTOR signal pathway on chronic neuropathic pain (CNP) and spinal microglia in a rat model of chronic constriction injury (CCI). METHODS: Male SD rats were assigned into control, sham, CCI, wortmannin, dimethyl sulfoxide (DMSO) and wortmannin-positive control groups. Paw withdrawal mechanical threshold (PWMT) and thermal withdrawal latency (TWL) were recorded. qRT-PCR and Western blotting were used to detect PI3K, Akt and mTOR expressions and their phosphorylation...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877966/t-cell-mediation-of-pregnancy-analgesia-affecting-chronic-pain-in-mice
#16
Sarah F Rosen, Boram Ham, Shannon Drouin, Nadia Boachie, Anne-Julie Chabot-Dore, Jean-Sebastien Austin, Luda Diatchenko, Jeffrey S Mogil
It has been consistently reported that many female chronic pain sufferers have an attenuation of symptoms during pregnancy. Rats display increased pain tolerance during pregnancy, due to an increase in opioid receptors in the spinal cord. These past studies did not consider the role of non-neuronal cells, now appreciated to play an important role in chronic pain processing. Using an inflammatory (complete Freund's adjuvant) or neuropathic (spared nerve injury) model of persistent pain, we observe that young adult female mice in early pregnancy switch from a micgrolia-independent to a microglia-dependent pain hypersensitivity mechanism...
September 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28874746/rgma-inhibition-with-human-monoclonal-antibodies-promotes-regeneration-plasticity-and-repair-and-attenuates-neuropathic-pain-after-spinal-cord-injury
#17
Andrea J Mothe, Nardos G Tassew, Alirezha P Shabanzadeh, Romeo Penheiro, Robin J Vigouroux, Lili Huang, Christine Grinnell, Yi-Fang Cui, Emma Fung, Philippe P Monnier, Bernhard K Mueller, Charles H Tator
Traumatic spinal cord injury (SCI) causes a cascade of degenerative events including cell death, axonal damage, and the upregulation of inhibitory molecules which prevent regeneration and limit recovery. Repulsive guidance molecule A (RGMa) is a potent neurite growth inhibitor in the central nervous system, exerting its repulsive activity by binding the Neogenin receptor. Here, we show for the first time that inhibitory RGMa is markedly upregulated in multiple cell types after clinically relevant impact-compression SCI in rats, and importantly, also in the injured human spinal cord...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871264/neuroinflammation-bone-marrow-stem-cells-and-chronic-pain
#18
REVIEW
Yul Huh, Ru-Rong Ji, Gang Chen
Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS) plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG)], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain), and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL)-1β, IL-6, CCL2, and CXCL1]...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28865126/circadian-control-of-pain-and-neuroinflammation
#19
REVIEW
Julia P Segal, Kaitlyn A Tresidder, Charvi Bhatt, Ian Gilron, Nader Ghasemlou
The importance of a neuroinflammatory response to the development and maintenance of inflammatory and neuropathic pain have been highlighted in recent years. Inflammatory cells contributing to this response include circulating immune cells such as monocytes, T and B lymphocytes, and neutrophils, as well as microglia in the central nervous system. Pain signals are transmitted via sensory neurons in the peripheral nervous system, which express various receptors and channels that respond to mediators secreted from these inflammatory cells...
September 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28844566/role-of-trka-signalling-and-mast-cells-in-the-initiation-of-osteoarthritis-pain-in-the-monoiodoacetate-model
#20
J Sousa-Valente, L Calvo, V Vacca, R Simeoli, J C Arévalo, M Malcangio
OBJECTIVE: Aiming to delineate novel neuro-immune mechanisms for NGF/TrkA signalling in osteoarthritis (OA) pain, we evaluated inflammatory changes in the knee joints following injection of monoiodoacetate (MIA) in mice carrying a TrkA receptor mutation (P782S; TrkA KI mice). METHOD: In behavioural studies we monitored mechanical hypersensitivity following intra-articular MIA and oral prostaglandin D2 (PGD2) synthase inhibitor treatments. In immunohistochemical studies we quantified joint mast cell numbers, calcitonin gene-related peptide expression in synovia and dorsal root ganglia, spinal cord neuron activation and microgliosis...
August 24, 2017: Osteoarthritis and Cartilage
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