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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
#1
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
#2
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
#3
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
#4
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 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
#5
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
#6
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
#7
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
#8
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
#9
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...
June 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28652182/ulinastatin-attenuates-neuropathic-pain-via-the-atp-p2y2-receptor-pathway-in-rat-models
#10
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
https://www.readbyqxmd.com/read/28649222/highly-selective-cyclooxygenase-1-inhibitors-p6-and-mofezolac-counteract-inflammatory-state-both-in-vitro-and-in-vivo-models-of-neuroinflammation
#11
Rosa Calvello, Dario Domenico Lofrumento, Maria Grazia Perrone, Antonia Cianciulli, Rosaria Salvatore, Paola Vitale, Francesco De Nuccio, Laura Giannotti, Giuseppe Nicolardi, Maria Antonietta Panaro, Antonio Scilimati
Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28648042/-effects-of-lappaconitine-on-pain-and-inflammatory-response-of-severely-burned-rats-and-the-mechanism
#12
C L Yang, Z R Wei, T H Zhang, X Q Zeng, B H Wu
Objective: To explore the effects of lappaconitine (LA) on pain and inflammatory response of severely burned rats and the mechanism. Methods: Forty SD rats were divided into healthy+ normal saline group, sham injury+ normal saline group, pure burn group, burn+ LA group, and healthy+ LA group according to the random number table (the same dividing method below), with 8 rats in each group. Rats in pure burn and burn+ LA groups were inflicted with about 32% total body surface area deep partial-thickness scald (hereinafter referred to as burn) on the back and right hind...
June 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28626198/the-therapeutic-effect-of-dexmedetomidine-on-rat-diabetic-neuropathy-pain-and-the-mechanism
#13
Yuecheng Lu, Baohua Lin, Junmin Zhong
Diabetic neuropathy pain (DNP) is a common chronic complication of diabetes characterized by spontaneous pain, hyperalgesia and allodynia. Dexmedetomidine is a selective α2 adrenergic agonist that relieves sympathetic nervous tension and reduces the release of glutamate. Thus, it is possible that dexmedetomidine may relieve DNP as well. In this study, we examined the effect of dexmedetomidine on DNP in the presence or absence of the α2 adrenergic antagonist yohimbine in rats utilizing a streptozotocin (STZ)-induced diabetes as a model of DNP...
June 14, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28625489/diosmin-reduces-chronic-constriction-injury-induced-neuropathic-pain-in-mice
#14
Mariana M Bertozzi, Ana C Rossaneis, Victor Fattori, Daniela T Longhi-Balbinot, Andressa Freitas, Fernando Q Cunha, José C Alves-Filho, Thiago M Cunha, Rubia Casagrande, Waldiceu A Verri
Injury or dysfunction of somatosensory system induces a complex syndrome called neuropathic pain, which still needs adequate pharmacological control. The current pharmacological treatments were in part developed from natural compounds. Flavonoids are natural polyphenolic molecules presenting varied biological activities and low toxicity. The flavonoid diosmin is a safe compound with good tolerability and low toxicity. This study evaluated the antinociceptive effect of diosmin in the sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain model...
June 15, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28615626/neuronal-p2x7-receptor-induced-reactive-oxygen-species-production-contributes-to-nociceptive-behavior-in-mice
#15
Frances M Munoz, Ruby Gao, Yuzhen Tian, Brian A Henstenburg, James E Barrett, Huijuan Hu
ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R-induced pain remains unexplored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615336/prevention-and-reversal-of-latent-sensitization-of-dorsal-horn-neurons-by-glial-blockers-in-a-model-of-low-back-pain-in-male-rats
#16
Juanjuan Zhang, Siegfried Mense, Rolf-Detlef Treede, Ulrich Hoheisel
In an animal model of non-specific low back pain, recordings from dorsal horn neurons were made to investigate the influence of glial cells in the central sensitization process. To induce a latent sensitization of the neurons, nerve growth factor (NGF) was injected into the multifidus muscle; the manifest sensitization to a second NGF injection 5 days later was used as a read-out. The sensitization manifested in increased resting activity and in an increased proportion of neurons responding to stimulation of deep somatic tissues...
June 14, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28611665/toll-like-receptor-4-in-paraventricular-nucleus-mediates-visceral-hypersensitivity-induced-by-maternal-separation
#17
Hui-Li Tang, Gongliang Zhang, Ning-Ning Ji, Lei Du, Bin-Bin Chen, Rong Hua, Yong-Mei Zhang
Neonatal maternal separation (MS) is a major early life stress that increases the risk of emotional disorders, visceral pain perception and other brain dysfunction. Elevation of toll-like receptor 4 (TLR4) signaling in the paraventricular nucleus (PVN) precipitates early life colorectal distension (CRD)-induced visceral hypersensitivity and pain in adulthood. The present study aimed to investigate the role of TLR4 signaling in the pathogenesis of postnatal MS-induced visceral hypersensitivity and pain during adulthood...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28603455/tetramethylpyrazine-attenuates-periorbital-allodynia-and-neuroinflammation-in-a-model-of-traumatic-brain-injury
#18
Zhijing Wang, Qi Wang, Cuijie Wang, Xiuzhen Xu, Hongmei Yu
BACKGROUND: Traumatic brain injury (TBI) is a public health issue. As the major complaint in 51% of TBI patients, chronic pain is an important aspect in TBI treatment. Tetramethylpyrazine (TMP) is an important compound in Ligustrazine, an analgesic drug in traditional Chinese medicine, but its potential in relieving pain symptom in TBI has not been tested. We established a TBI mouse model with controlled cortical impact (CCI), and measured periorbital hypersensitivity with von Frey monofilaments...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28598083/-expressions-of-spinal-macrophage-colony-stimulating-factor-and-its-receptor-csf-1r-in-the-development-ofcomplicated-regional-pain-symptom-i
#19
Zhi-Min Liao, Yu-Ying Tang, Yang-Chun Zheng, Dan Xu
OBJECTIVES: To study the changes of mechanical allodynia and temperature hyperalgesia, as well as the expression of the spinal macrophage colony stimulating factor (M-CSF) and its receptor CSF-1R during the development of complicated regional pain symptom I(CRPS I). METHODS: The animal model of CRPS I was established using prolonged ischemia-reperfusion injury of rodent left hindpaw. The mechanical allodynia and temperature hyperalgesia of ipsilateral hindpaw were continuously measured for 14 d after reperfusion, and the expressions of spinal M-CSF and CSF-1R in ipsilateral spinal cord horn were measured with immunofluorescence technique on day 3, day 7 and day 14 after reperfusion...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28598070/-helminth-derived-immunomodulatory-glycan-lnfp3-impairs-pathogenesis-of-peripheral-neuropathic-pain-and-spinal-glial-activation
#20
You-Quan Ding, Hhong-Yi Ren, Xia Xiao, Xuan-Yang Li, Jian-Guo Qi
OBJECTIVES: To investigate the effect of helminth-derived immunomodulatory glycan lacto-N-fucopentaose3(LNFP3) on the pathogenesis of neuropathic pain and spinal glial activation in the corresponding time windows after adult rat tibial nerve permanent transection (modified spared nerve injury, mSNI). METHODS: Ten weeks old male adult Sprague-Dawley (SD) rats weighing 250-300 g were randomly grouped into four groups: sham-operated group (n =6), mSNI group (n =6), mSNI plus bovine serum albumin (BSA) group (n =12) and mSNI plus LNFP3 group (n=12)...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
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