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https://www.readbyqxmd.com/read/29913949/long-term-pain-neuroinflammation-and-glial-activation
#1
Elisabeth Hansson
Nociceptive and neuropathic pain signals are known to result from noxious stimuli, which are converted into electrical impulses within tissue nociceptors. There is a complex equilibrium of pain-signalling and pain-relieving pathways connecting PNS and CNS. Drugs against long-term pain are today directed against increased neuronal excitability, mostly with less success. An injury often starts with acute physiological pain, which becomes inflammatory, nociceptive, or neuropathic, and may be transferred into long-term pain...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913894/evaluation-of-a-novel-chemokine-receptor-2-ccr2-antagonist-in-painful-diabetic-polyneuropathy
#2
Jarkko Kalliomäki, Bror Jonzon, Karin Huizar, Michael O'Malley, Anita Andersson, David M Simpson
Background and aims Preclinical data suggest that the chemokine receptor 2 (CCR2) is involved in the pathophysiology of neuropathic pain through modulation of neuronal excitability, synaptic transmission and activation of spinal cord microglia. CCR2-antagonists have shown to be effective in preclinical models of neuropathic pain. The aim of this study was to evaluate the analgesic efficacy, safety and tolerability of a novel CCR2-antagonist, AZD2423, in patients with painful diabetic neuropathy (PDN). Methods This was a double-blind, randomized, parallel-group, multi-center study in patients with symmetric distal sensory polyneuropathy due to type 1 or 2 diabetes and duration of neuropathic pain between 3 months and 5 years...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913808/sortilins-in-neuropathic-pain
#3
M Richner, O J Bjerrum, Y De Koninck, A Nykjaer, C B Vaegter
Background/aims The molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913704/cathepsin-s-is-increased-in-cerebrospinal-fluid-from-patients-with-neuropathic-pain-a-support-of-the-microglia-hypothesis-in-humans
#4
Torsten Gordh, Anne-Li Lind, Constantin Bodolea, Ellen Hewitt, Anders Larsson
Aims Cathepsin S has been reported to be a biomarker of spinal microglial activation, a process suggested to be involved in the pathophysiology of chronic neuropathic pain. So far this has been shown only in animal experiments. The aim of this study was to investigate the concentrations of cathepsin S in human cerebrospinal fluid (CSF) samples from a well-defined patient cohort suffering from neuropathic pain as compared to controls. Methods CSF samples from patients suffering from chronic neuropathic pain (n = 14) were analyzed for cathepsin S levels using commercial sandwich ELISAs (DY1183, R&D Systems, Minneapolis, MN, USA)...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913243/spinal-inhibition-of-p2xr-or-p38-signaling-disrupts-hyperalgesic-priming-in-male-but-not-female-mice
#5
Candler Paige, Gayathri Batchalli Maruthy, Galo Mejia, Gregory Dussor, Theodore Price
Recent studies have demonstrated sexual dimorphisms in the mechanisms contributing to the development of chronic pain. Here we tested the hypothesis that microglia might preferentially regulate hyperalgesic priming in male mice. We based this hypothesis on evidence that microglia preferentially contribute to neuropathic pain in male mice via ionotropic purinergic receptor (P2XR) or p38 mitogen activated protein kinase (p38) signaling. Mice given a single priming injection of the soluble human interleukin-6 receptor (IL-6r) and then a second injection of prostaglandin E2 (PGE2 ), which unmasks hyperalgesic priming, show a significant increase in levels of activated microglia at 3h following the PGE2 injection in both male and female mice...
June 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29911589/perspectives-in-pain-research-2014-neuroinflammation-and-glial-cell-activation-the-cause-of-transition-from-acute-to-chronic-pain
#6
Brian E Cairns, Lars Arendt-Nielsen, Paola Sacerdote
Background It is unknown why an acute pain condition under various circumstances can transition into a chronic pain condition. There has been a shift towards neuroinflammation and hence glial cell activations specifically in the dorsal root ganglion and spinal cord as a mechanism possibly driving the transition to chronic pain. This has led to a focus on non-neuronal cells in the peripheral and central nervous system. Besides infiltrating macrophages, Schwann cells and satellite glial cells release cytokines and therefore important mechanisms in the maintenance of pain...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29909203/neuronal-complement-cascade-drives-bone-cancer-pain-via-c3r-mediated-microglial-activation
#7
Xiaoxia Huang, Jinyuan Li, Jin Xie, Yang Li, Yan Gao, Xiaohui Li, Xueqin Xu, Ruoshi Shi, Wanjun Yao, Changbin Ke
Activation of spinal cord microglia is crucial for the development of bone cancer pain (BCP). The essential signal between neuronal excitability and microglial activation is not fully understood. In the present study, carcinoma implantation into tibia was used to induce BCP and RNAi-lentivirus was injected into spinal cord to knock down C1, C2 or C3 of complement cascade. We showed that C1, C2 and C3 co-localized in the same neurons and increased in cancer-bearing rats along with microglial activation. Knocked down of C1, C2 or C3 inhibited microglial activation and prevented the development of cancer-induced bone pain...
June 14, 2018: Brain Research
https://www.readbyqxmd.com/read/29889119/targeting-toll-like-receptor-4-tlr4-emerging-therapeutic-target-for-persistent-pain-states
#8
Kelly Bruno, Sarah A Woller, Yury I Miller, Tony L Yaksh, Mark Wallace, Graham Beaton, Krishnan Chakravarthy
Toll-like receptors (TLRs) are a family of pattern-recognition receptors that initiate signaling in innate and adaptive immune pathways. The highly conserved family of transmembrane proteins are comprised of an extracellular domain that recognizes exogenous and endogenous danger molecules and an ectodomain that activates downstream pathways in response. Recent studies suggest that continuous activation or dysregulation of TLR signaling may contribute to chronic disease states. The receptor is located not only on inflammatory cells (meningeal and peripheral macrophages) but on neuraxial glia (microglia and astrocytes), schwann cells, fibroblasts, dorsal root ganglia and dorsal horn neurons...
June 7, 2018: Pain
https://www.readbyqxmd.com/read/29888808/changes-in-proinflammatory-cytokines-neuropeptides-and-microglia-in-an-animal-model-of-monosodium-iodoacetate-induced-hip-osteoarthritis
#9
Yuya Kawarai, Sumihisa Orita, Junichi Nakamura, Shuichi Miyamoto, Miyako Suzuki, Kazuhide Inage, Shigeo Hagiwara, Takane Suzuki, Takayuki Nakajima, Tsutomu Akazawa, Seiji Ohtori
The aim of this study was to investigate the local production of proinflammatory cytokines, pain- related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). Seventy-five Sprague Dawley rats were used, including 25 controls and 50 injected into the right hip joints (sham group, injected with 25 µl of sterile saline: N =25; and monosodium iodoacetate (MIA) group, injected with 25 µl of sterile saline with 2 mg of MIA: N = 25). We measured the local production of TNF-α, immunoreactive (-ir) neurons for calcitonin gene-related peptide (CGRP) and growth associated protein-43 (GAP-43) in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule-1 (Iba-1) in the dorsal horn of spinal cord, on post-induction days 7, 14, 28, 42, and 56 (N = 5 rats/group/time point)...
June 11, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29886243/ibudilast-produces-anti-allodynic-effects-at-the-persistent-phase-of-peripheral-or-central-neuropathic-pain-in-rats-different-inhibitory-mechanism-on-spinal-microglia-from-minocycline-and-propentofylline
#10
Masahide Fujita, Ryuta Tamano, Sosuke Yoneda, Shigeki Omachi, Erika Yogo, Masatomo Rokushima, Shunji Shinohara, Gaku Sakaguchi, Minoru Hasegawa, Toshiyuki Asaki
Microglia exhibit various activation phenotypes in the spinal cord after peripheral nerve injury, and promote neuropathic pain. Ibudilast is a phosphodiesterase inhibitor with anti-inflammatory activity, but its effect on activated microglia in chronic neuropathic pain is poorly understood. We investigated whether ibudilast was effective on established allodynia associated with activated microglial phenotypes in two rat models of peripheral and central neuropathic pain. A single intrathecal injection of ibudilast (25μg) inhibited established allodynia on days 7-21 after sciatic nerve injury in rats...
June 7, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29882480/dehydrocorydaline-attenuates-bone-cancer-pain-by-shifting-microglial-m1-m2-polarization-toward-the-m2-phenotype
#11
Wenwen Huo, Ying Zhang, Yue Liu, Yishan Lei, Rao Sun, Wei Zhang, Yulin Huang, Yanting Mao, Chenchen Wang, Zhengliang Ma, Xiaoping Gu
Bone cancer pain remains a major challenge in patients with primary or metastatic bone cancer due to a lack of understanding the mechanisms. Previous studies have revealed the two distinct functional polarization states of microglia (classically activated M1 and alternatively activated M2) in the spinal cord in nerve injury-induced neuropathic pain. However, whether microglia in the spinal cord polarize to M1 and M2 phenotypes and contribute to the development of bone cancer pain remains unclear. In this study, we used a mouse model with bone cancer to characterize the M1/M2 polarization of microglia in the spinal cord during the development of bone cancer pain, and investigated the antinociceptive effects of dehydrocorydaline, an alkaloidal component isolated from Rhizoma corydalis on bone cancer pain...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29879988/ammoxetine-attenuates-diabetic-neuropathic-pain-through-inhibiting-microglial-activation-and-neuroinflammation-in-the-spinal-cord
#12
Ting-Ting Zhang, Rui Xue, Shi-Yong Fan, Qiong-Yin Fan, Lei An, Juan Li, Lei Zhu, Yu-Hua Ran, Li-Ming Zhang, Bo-Hua Zhong, Yun-Feng Li, Cai-Ying Ye, You-Zhi Zhang
BACKGROUND: Diabetic neuropathic pain (DNP) is a common and distressing complication in patients with diabetes, and the underlying mechanism remains unclear. Tricyclic antidepressants (TCAs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line drugs for DNP. Ammoxetine is a novel and potent SNRI that exhibited a strong analgesic effect on models of neuropathic pain, fibromyalgia-related pain, and inflammatory pain in our primary study. The present study was undertaken to investigate the chronic treatment properties of ammoxetine on DNP and the underlying mechanisms for its effects...
June 7, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29858667/bone-mesenchymal-stem-cells-attenuate-radicular-pain-by-inhibiting-microglial-activation-in-a-rat-noncompressive-disk-herniation-model
#13
Xiaodong Huang, Weiheng Wang, Xilin Liu, Yanhai Xi, Jiangming Yu, Xiangqun Yang, Xiaojian Ye
Spinal disk herniation can induce radicular pain through chemical irritation caused by proinflammatory and immune responses. Bone marrow mesenchymal stem cells (BMSCs) are a unique type of adult stem cell with the functions of suppressing inflammation and modulating immune responses. This study was undertaken to observe the effect of intrathecal BMSCs on the treatment of mechanical allodynia and the suppression of microglial activation in a rat noncompressive disk herniation model. The model was induced by the application of nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG)...
June 1, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29858055/gene-therapy-for-neuropathic-pain-through-sirna-irf5-gene-delivery-with-homing-peptides-to-microglia
#14
Tomoya Terashima, Nobuhiro Ogawa, Yuki Nakae, Toshiyuki Sato, Miwako Katagi, Junko Okano, Hiroshi Maegawa, Hideto Kojima
Astrocyte- and microglia-targeting peptides were identified and isolated using phage display technology. A series of procedures, including three cycles of both in vivo and in vitro biopanning, was performed separately in astrocytes and in M1 or M2 microglia, yielding 50-58 phage plaques in each cell type. Analyses of the sequences of this collection identified one candidate homing peptide targeting astrocytes (AS1[C-LNSSQPS-C]) and two candidate homing peptides targeting microglia (MG1[C-HHSSSAR-C] and MG2[C-NTGSPYE-C])...
June 1, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29847797/inhibition-of-neuroinflammation-by-aibp-spinal-effects-upon-facilitated-pain-states
#15
Sarah A Woller, Soo-Ho Choi, Eun Jung An, Hann Low, Dina A Schneider, Roshni Ramachandran, Jungsu Kim, Yun Soo Bae, Dmitri Sviridov, Maripat Corr, Tony L Yaksh, Yury I Miller
Apolipoprotein A-I binding protein (AIBP) reduces lipid raft abundance by augmenting the removal of excess cholesterol from the plasma membrane. Here, we report that AIBP prevents and reverses processes associated with neuroinflammatory-mediated spinal nociceptive processing. The mechanism involves AIBP binding to Toll-like receptor-4 (TLR4) and increased binding of AIBP to activated microglia, which mediates selective regulation of lipid rafts in inflammatory cells. AIBP-mediated lipid raft reductions downregulate LPS-induced TLR4 dimerization, inflammatory signaling, and expression of cytokines in microglia...
May 29, 2018: Cell Reports
https://www.readbyqxmd.com/read/29793601/adiponectin-regulates-thermal-nociception-in-a-mouse-model-of-neuropathic-pain
#16
L Sun, H Li, L W Tai, P Gu, C W Cheung
BACKGROUND: Adiponectin, a cytokine secreted by adipocytes, plays an important role in regulating glucose and lipid metabolism. However, the role of adiponectin in pain conditions is largely unknown. This study aimed to identify the role and mechanism of adiponectin in nociceptive sensitivity under physiological and pathological states utilising adiponectin knockout (KO) mice. METHODS: Wild type (WT) and adiponectin KO mice were subjected to partial sciatic nerve ligation (pSNL) or sham operation...
June 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29770147/koumine-attenuates-neuroglia-activation-and-inflammatory-response-to-neuropathic-pain
#17
Gui-Lin Jin, Sai-Di He, Shao-Mei Lin, Li-Mian Hong, Wan-Qing Chen, Ying Xu, Jian Yang, Su-Ping Li, Chang-Xi Yu
Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine-an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.-has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI) neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro ...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29763613/neuroprotective-effect-of-duloxetine-in-a-mouse-model-of-diabetic-neuropathy-role-of-glia-suppressing-mechanisms
#18
Mona K Tawfik, Seham A Helmy, Dahlia I Badran, Sawsan A Zaitone
AIMS: Painful diabetic neuropathy (PDN) is one of the most frequent complications of diabetes and the current therapies have limited efficacy. This study aimed to study the neuroprotective effect of duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), in a mouse model of diabetic neuropathy. MAIN METHODS: Nine weeks after developing of PDN, mice were treated with either saline or duloxetine (15 or 30 mg/kg) for four weeks. The effect of duloxetine was assessed in terms of pain responses, histopathology of sciatic nerve and spinal cord, sciatic nerve growth factor (NGF) gene expression and on the spinal expression of astrocytes (glial fibrillary acidic protein, GFAP) and microglia (CD11 b)...
May 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29763588/glycyrrhizin-ameliorates-inflammatory-pain-by-inhibiting-microglial-activation-mediated-inflammatory-response-via-blockage-of-the-hmgb1-tlr4-nf-kb-pathway
#19
Xiaojuan Sun, Hongyou Zeng, Qingsong Wang, Qingwen Yu, Jianxiong Wu, You Feng, Peng Deng, Hongxing Zhang
Chronic inflammatory pain is a severe clinical problem that greatly affects patients' quality of life and causes huge economic burden. Microglia-mediated neuroinflammation exerts critical roles in the pathogenic progression of inflammatory pain. Recent evidence corroborates the anti-inflammatory and neuroprotective efficacy of glycyrrhizin; however, its function in inflammatory pain remains poorly elucidated. In the present study, glycyrrhizin suppressed LPS-induced activation of microglial cell BV2 by inhibiting NO production and expression of microglial marker IBA-1...
May 12, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29730970/spinal-glial-adaptations-occur-in-a-minimally-invasive-mouse-model-of-endometriosis-potential-implications-for-lesion-etiology-and-persistent-pelvic-pain
#20
Kelsi N Dodds, Elizabeth A H Beckett, Susan F Evans, Mark R Hutchinson
Glial adaptations within the central nervous system are well known to modulate central sensitization and pain. Recently, it has been suggested that activity of glial-related proinflammatory cytokines may potentiate peripheral inflammation, via central neurogenic processes. However, a role for altered glial function has not yet been investigated in the context of endometriosis, a chronic inflammatory condition in women associated with peripheral lesions, often manifesting with persistent pelvic pain. Using a minimally invasive mouse model of endometriosis, we investigated associations between peripheral endometriosis-like lesions and adaptations in central glial reactivity...
January 1, 2018: Reproductive Sciences
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