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https://www.readbyqxmd.com/read/28822786/leptin-is-essential-for-spinal-microglial-activation-and-neuropathic-pain-after-preganglionic-cervical-root-avulsion
#1
Kai-Ting Chang, Yi-Lo Lin, Chi-Te Lin, Chen-Jei Hong, May-Jywan Tsai, Wen-Cheng Huang, Yang-Hsin Shih, Yi-Yen Lee, Henrich Cheng, Ming-Chao Huang
AIMS: Preganglionic cervical root avulsion (PCRA) affects both the peripheral and central nervous systems and is often associated with neuropathic pain. Unlike peripheral nerve injuries (PNI), central lesions caused by disruption of cervical roots from the spinal cord following PCRA contribute to the generation of neuropathic pain. Leptin is involved in the development of neuropathic pain after PNI by affecting neurons. However, whether leptin is involved in microglial activation leading to neuropathic pain after PCRA is unknown...
August 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/28797764/inflammatory-pain-assessment-in-the-arthritis-of-the-temporomandibular-joint-in-rats-a-comparison-between-two-phlogistic-agents
#2
Joana Cláudia Bezerra de Araújo, Delane Viana Gondim, André Luiz Cunha Cavalcante, Mario Roberto Pontes Lisboa, Gerly Anne de Castro Brito, Mariana Lima Vale
Temporomandibular joint (TMJ) disorders are a group of conditions that result in TMJ pain, which frequently limits basic daily activities. Experimental models that allow the study of the mechanisms underlying these inflammatory and pain conditions are of great clinical relevance. The aim of this study was to evaluate nociception, inflammation and participation of the macrophage/microglia cells in the arthritis of the TMJ induced by two phlogistic agents. 84 rats were divided into 2 groups: Zy, which received zymosan intra-articularly, or Cg, which received carrageenan intra-articularly...
August 8, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28794655/p2y12-and-p2y13-receptors-involved-in-adp%C3%AE-s-induced-the-release-of-il-1%C3%AE-il-6-and-tnf-%C3%AE-from-cultured-dorsal-horn-microglia
#3
Pei-Wen Liu, Ming-Xia Yue, Rui Zhou, Juan Niu, Du-Juan Huang, Tao Xu, Pei Luo, Xiao-Hong Liu, Jun-Wei Zeng
OBJECTIVE: P2 receptors have been implicated in the release of neurotransmitter and pro-inflammatory cytokines due to their response to neuroexcitatory substances in the microglia. Dorsal horn P2Y12 and P2Y13 receptors are involved in the development of pain behavior induced by peripheral nerve injury. However, it is not known whether P2Y12 and P2Y13 receptors activation is associated with the expression and the release of interleukin-1B (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in cultured dorsal spinal cord microglia...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28793053/cerebrospinal-fluid-contacting-nucleus-mediates-nociception-via-release-of-fractalkine
#4
Q Q Zhou, S S Chen, Q Q Zhang, P F Liu, H Z Fang, Y Yang, L C Zhang
Increasing evidence suggests that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia...
August 7, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28791619/vimentin-promotes-astrocyte-activation-after-chronic-constriction-injury
#5
Pengfei Xue, Liming Chen, Xiongsong Lu, Jinlong Zhang, Guofeng Bao, Guanhua Xu, Yuyu Sun, Xiaofeng Guo, Jiawei Jiang, Haiyan Gu, Zhiming Cui
Vimentin, among the family of the intermediate filament, plays as the organizer of some critical proteins involved in migration, attachment, and cell signaling. 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 kinase), and vimentin...
August 8, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28776289/spinal-cx3cl1-cx3cr1-may-not-directly-participate-in-the-development-of-morphine-tolerance-in-rats
#6
Yawen Peng, Genhua Guo, Bin Shu, Daiqiang Liu, Peng Su, Xuming Zhang, Feng Gao
CX3CL1 (fractalkine), the sole member of chemokine CX3C family, is implicated in inflammatory and neuropathic pain via activating its receptor CX3CR1 on neural cells in spinal cord. However, it has not been fully elucidated whether CX3CL1 or CX3CR1 contributes to the development of morphine tolerance. In this study, we found that chronic morphine exposure did not alter the expressions of CX3CL1 and CX3CR1 in spinal cord. And neither exogenous CX3CL1 nor CX3CR1 inhibitor could affect the development of morphine tolerance...
August 3, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28772216/minocycline-attenuates-the-development-of-diabetic-neuropathy-by-inhibiting-spinal-cord-notch-signaling-in-rat
#7
Cheng Yang, Jie Gao, Banglin Wu, Nuo Yan, Hui Li, Yiqing Ren, Yufei Kan, Jiamin Liang, Yang Jiao, Yonghao Yu
We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28755135/macrophage-derived-hmgb1-as-a-pain-mediator-in-the-early-stage-of-acute-pancreatitis-in-mice-targeting-rage-and-cxcl12-cxcr4-axis
#8
Yuhei Irie, Maho Tsubota, Hiroyasu Ishikura, Fumiko Sekiguchi, Yuka Terada, Toshifumi Tsujiuchi, Keyue Liu, Masahiro Nishibori, Atsufumi Kawabata
Extracellular high mobility group box 1 (HMGB1) activates the receptor for advanced glycation end products (RAGE) or Toll-like receptor 4 (TLR4) and forms a heterocomplex with CXCL12 that strongly activates CXCR4, promoting inflammatory and pain signals. In the present study, we investigated the role of HMGB1 in pancreatic pain accompanying cerulein-induced acute pancreatitis in mice. Abdominal referred hyperalgesia accompanying acute pancreatitis occurred within 1 h after 6 hourly injections of cerulein. The anti-HMGB1 neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, abolished the cerulein-induced referred hyperalgesia, but not pancreatitis itself...
July 28, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28747388/neuronal-p2x7-receptors-revisited-do-they-really-exist
#9
Peter Illes, Tahir Muhammad Khan, Patrizia Rubini
P2X7 receptors (Rs) constitute a subclass of ATP-sensitive ionotropic receptors (P2X1-P2X7). P2X7Rs have many distinguishing features, mostly based on their long intracellular C terminus regulating trafficking to the cell membrane, protein-protein interactions, and post-translational modification. Their C-terminal tail is especially important in enabling the transition from the nonselective ion channel mode to a membrane pore allowing the passage of large molecules. There is an ongoing dispute on the existence of neuronal P2X7Rs with consequences for our knowledge on their involvement in neuroinflammation, aggravating stroke, temporal lobe epilepsy, neuropathic pain, and various neurodegenerative diseases...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28746078/spinal-microglia-are-required-for-long-term-maintenance-of-neuropathic-pain
#10
Stefania Echeverry, Xiang Qun Shi, Mu Yang, Hao Huang, YiChen Wu, Louis-Etienne Lorenzo, Jimena Perez-Sanchez, Robert P Bonin, Yves De Koninck, Ji Zhang
While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28722693/ikk-nf-%C3%AE%C2%BAb-dependent-satellite-glia-activation-induces-spinal-cord-microglia-activation-and-neuropathic-pain-after-nerve-injury
#11
Hyoungsub Lim, Hyunkyoung Lee, Kyungchul Noh, Sung Joong Lee
Increasing evidence indicates that both microglia and satellite glial cell (SGC) activation play causal roles in neuropathic pain development after peripheral nerve injury; however, the activation mechanisms and their contribution to neuropathic pain remain elusive. To address this issue, we generated Ikkβ conditional knockout mice (Cnp-Cre/Ikkβ; cIkkβ) in which IKK/NF-κB-dependent proinflammatory SGC activation was abrogated. In these mice, nerve injury-induced spinal cord microglia activation and pain hypersensitivity were significantly attenuated compared to those in control mice...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28720702/identification-of-a-vesicular-atp-release-inhibitor-for-the-treatment-of-neuropathic-and-inflammatory-pain
#12
Yuri Kato, Miki Hiasa, Reiko Ichikawa, Nao Hasuzawa, Atsushi Kadowaki, Ken Iwatsuki, Kazuhiro Shima, Yasuo Endo, Yoshiro Kitahara, Tsuyoshi Inoue, Masatoshi Nomura, Hiroshi Omote, Yoshinori Moriyama, Takaaki Miyaji
Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment of pathological neuropathic and inflammatory pain. However, such therapeutic analgesic agents have yet to be developed. In the present study, we demonstrated that clodronate, a first-generation bisphosphonate with comparatively fewer side effects than traditional treatments, significantly attenuates neuropathic and inflammatory pain unrelated to bone abnormalities via inhibition of vesicular nucleotide transporter (VNUT), a key molecule for the initiation of purinergic chemical transmission...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716092/the-role-of-microglial-p2x7-modulation-of-cell-death-and-cytokine-release
#13
Yingbo He, Natalie Taylor, Lawrence Fourgeaud, Anindya Bhattacharya
BACKGROUND: ATP-gated P2X7 is a non-selective cation channel, which participates in a wide range of cellular functions as well as pathophysiological processes including neuropathic pain, immune response, and neuroinflammation. Despite its abundant expression in microglia, the role of P2X7 in neuroinflammation still remains unclear. METHODS: Primary microglia were isolated from cortices of P0-2 C57BL/6 wild-type or P2X7 knockout (P2X7(-/-)) mouse pups. Lipopolysaccharide, lipopolysaccharide plus IFNγ, or IL4 plus IL13 were used to polarize microglia to pro-inflammatory or anti-inflammatory states...
July 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28709913/upregulation-of-neuronal-kynurenine-3-monooxygenase-mediates-depression-like-behavior-in-a-mouse-model-of-neuropathic-pain
#14
Geoffroy Laumet, Wenjun Zhou, Robert Dantzer, Jules D Edralin, XiaoJiao Huo, David P Budac, Jason C O'Connor, Anna W Lee, Cobi J Heijnen, Annemieke Kavelaars
Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain interleukin (IL)-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain...
July 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28671636/neuroprotective-and-anti-inflammatory-activities-of-allyl-isothiocyanate-through-attenuation-of-jnk-nf-%C3%AE%C2%BAb-tnf-%C3%AE-signaling
#15
Lalita Subedi, Ramu Venkatesan, Sun Yeou Kim
Allyl isothiocyanate (AITC), present in Wasabia japonica (wasabi), is an aliphatic isothiocyanate derived from the precursor sinigrin, which is a glucosinolate present in vegetables of the Brassica family. Traditionally, it has been used to treat rheumatic arthralgia, blood circulation, and pain. This study focuses on its anti-apoptotic activity through the regulation of lipopolysaccharide (LPS)-induced neuroinflammation. Furthermore, we assessed its neuroprotective efficacy, which it achieves through the upregulation of nerve growth factor (NGF) production...
July 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28669596/role-of-microglia-in-mechanical-allodynia-in-the-anterior-cingulate-cortex
#16
Keisuke Miyamoto, Kazuhiko Kume, Masahiro Ohsawa
Plastic changes that increase nociceptive transmission are observed in several brain regions under conditions of chronic pain. Synaptic plasticity in the anterior cingulate cortex (ACC) is particularly associated with neuropathic pain. Glial cells are considered candidates for the modulation of neural plastic changes in the central nervous system. In this study, we aimed to investigate the role of ACC glial cells in the development of neuropathic pain. First, we examined the expression of glial cells in the ACC of nerve-ligated mice...
June 21, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28668500/toll-like-receptor-4-p38-mapk-signaling-in-the-dorsal-horn-contributes-to-p2x4-receptor-activation-and-bdnf-over-secretion-in-cancer-induced-bone-pain
#17
Xiao-Wen Meng, Jian-Ling Gao, Jian-Ling Zuo, Li-Na Wang, Si-Lan Liu, Xiao-Hong Jin, Ming Yao, Michael Namaka
Our previous research suggested that the P2X4 receptor (P2X4R) expression in microglia was involved in the activation of toll-like receptor-4 (TLR4) in the dorsal horn in the rat model of cancer induced bone pain (CIBP). In this study, we focused on whether TLR4- mitogen-activated protein kinases, p38 (p38 MAPK) contributes to P2X4R activation and brain-derived neurotrophic factor (BDNF) over-secretion in CIBP. In in vitro experiment, the results showed that BDNF expression evoked by ATP stimulation was dependent on TLR4-p38...
June 28, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28663035/inhibition-of-interleukin-6-function-attenuates-the-central-sensitization-and-pain-behavior-induced-by-osteoarthritis
#18
Yuangui Lin, Lian Liu, Haixia Jiang, Jieshu Zhou, Yuying Tang
Chronic pain is the most prominent and disabling symptom in the patients with osteoarthritis (OA), and the underlying mechanism largely remains unclear. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization in several rodent models of chronic pain. The present study aims to elucidate the IL-6 mediated neurological adaptation in dorsal horn in the rat with monosodium iodoacetate (MIA) -induced OA. Significant upregulation of IL-6 expression was detected in the dorsal horn in the modeled rats...
June 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28654797/simvastatin-prevents-morphine-induced-tolerance-and-dependence-in-mice
#19
Nasim Sadat Pajohanfar, Ehsan Mohebbi, Ahmad Hosseini-Bandegharaei, Mohamadraza Amin, Golnaz Vaseghi, Bahareh Amin
BACKGROUND: Tolerance to analgesic effects of opioids and dependence to them are main concerns in the treatment of chronic pain conditions, limiting clinical application of these drugs. This study aimed to evaluate the effect of simvastatin on the morphine-induced tolerance and dependence in mice. MATERIAL AND METHODS: For this purpose, mice were treated with either daily morphine (20 mg/kg, s.c.) alone, or in combination with simvastatin (2.5, 5 and 10mg/kg, i...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28652182/ulinastatin-attenuates-neuropathic-pain-via-the-atp-p2y2-receptor-pathway-in-rat-models
#20
Ying Shi, Wanxiang Qin, Fachuan Nie, Huizhong Wen, Kaizhi Lu, Jian Cui
Ulinastatin, a serine protease inhibitor, which has anti-inflammatory properties and neuroprotective effects, is used to treat acute inflammatory disorders. Recent evidence indicates that administration of ulinastatin alleviates pain in rat model of neuropathic pain. However, its effect on neuropathic pain and the underlying mechanism requires further study. In this study, we evaluated the role of intrathecal administration of ulinastatin in rats with sciatic nerve ligation and observed the effect of ulinastatin on the ATP/P2Y2 receptor pathway...
June 23, 2017: Gene
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