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https://www.readbyqxmd.com/read/29447138/inflammation-in-the-pathophysiology-of-neuropathic-pain
#1
Claudia Sommer, Mathias Leinders, Nurcan Üçeyler
Peripheral nerve injuries and diseases often lead to pain persisting beyond the resolution of damage, indicating an active disease-promoting process, which may result in chronic pain. This is regarded as a maladaptive mechanism resulting from neuroinflammation that originally serves to promote regeneration and healing. Knowledge on these physiological and pathophysiological processes has accumulated over the last few decades and has started to yield potential therapeutic targets. Key players are macrophages, T-lymphocytes, cytokines, and chemokines...
March 2018: Pain
https://www.readbyqxmd.com/read/29445295/the-effect-of-exercise-frequency-on-neuropathic-pain-and-pain-related-cellular-reactions-in-the-spinal-cord-and-midbrain-in-a-rat-sciatic-nerve-injury-model
#2
Megumi Sumizono, Harutoshi Sakakima, Shotaro Otsuka, Takuto Terashi, Kazuki Nakanishi, Koki Ueda, Seiya Takada, Kiyoshi Kikuchi
Background: Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI) model. Materials and methods: Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group), CCI and low-frequency exercise (LFE group), CCI and no exercise (No-Ex group), and naive animals (control group)...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29444090/identification-of-fam173b-as-a-protein-methyltransferase-promoting-chronic-pain
#3
Hanneke L D M Willemen, Annemieke Kavelaars, Judith Prado, Mirjam Maas, Sabine Versteeg, Lara J J Nellissen, Jeshua Tromp, Rafael Gonzalez Cano, Wenjun Zhou, Magnus E Jakobsson, Jędrzej Małecki, George Posthuma, Abdella M Habib, Cobi J Heijnen, Pål Ø Falnes, Niels Eijkelkamp
Chronic pain is a debilitating problem, and insights in the neurobiology of chronic pain are needed for the development of novel pain therapies. A genome-wide association study implicated the 5p15.2 region in chronic widespread pain. This region includes the coding region for FAM173B, a functionally uncharacterized protein. We demonstrate here that FAM173B is a mitochondrial lysine methyltransferase that promotes chronic pain. Knockdown and sensory neuron overexpression strategies showed that FAM173B is involved in persistent inflammatory and neuropathic pain via a pathway dependent on its methyltransferase activity...
February 14, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29429030/nucleoside-reverse-transcriptase-inhibitors-nrtis-induce-pathological-pain-through-wnt5a-mediated-neuroinflammation-in-aging-mice
#4
Subo Yuan, Yuqiang Shi, Kaiwen Guo, Shao-Jun Tang
Highly Active Antiretroviral Therapy (HAART) has significantly contributed to the increase of HIV-infected survivors over 50 years of age. Unfortunately, patients are required to stay on long-term HAART, which may be causally related to the development of neurological problems such as chronic pain. Little is known about the contribution of HAART or its therapeutic agents to the pathogenesis of pain during aging. In this study, we determined the effect of nucleoside reverse transcriptase inhibitors (NRTIs) on the development of mechanical allodynia and the potential underlying mechanism in aging mice (15...
February 10, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29428215/spinal-pkc-activation-induced-neuronal-hmgb1-translocation-contributes-to-hyperalgesia-in-a-bone-cancer-pain-model-in-rats
#5
Kang An, Hui Rong, Huadong Ni, Chunyan Zhu, Longsheng Xu, Qianying Liu, Yajing Chen, Ying Zheng, Bing Huang, Ming Yao
Bone cancer pain (BCP) remains a serious complication of malignancy, which is an intractable clinical problem due to the gap in knowledge of its underlying mechanisms. Recent studies have demonstrated that the major involvement of neuroinflammation, particularly high-mobility group box 1 (HMGB1), which was identified as a late mediator of inflammation, in a number of pain conditions. However, the underlying mechanisms and functions of HMGB1 release in spinal cord, and its contributions to the development of BCP as well, are poorly understood...
February 8, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29423951/early-calp2-expression-and-microglial-activation-are-potential-inducers-of-spinal-il-6-upregulation-and-bilateral-pain-following-motor-nerve-injury
#6
Shao-Xia Chen, Shao-Kun Wang, Pei-Wen Yao, Guang-Jie Liao, Xiao-Dong Na, Yong-Yong Li, Wei-An Zeng, Xian-Guo Liu, Ying Zang
Previous work from our laboratory showed that motor nerve injury by lumbar 5 ventral root transection (L5-VRT) led to interleukin-6 (IL-6) overexpression in bilateral spinal cord, and that intrathecal administration of IL-6 neutralizing antibody delayed the induction of mechanical allodynia in bilateral hind paws. However, early events and upstream mechanisms underlying spinal IL-6 expression following L5-VRT require elucidation. The model of L5-VRT was used to induce neuropathic pain, which was assessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats...
February 9, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29421434/differential-spinal-and-supraspinal-activation-of-glia-in-a-rat-model-of-morphine-tolerance
#7
Viljami Jokinen, Yulia Sidorova, Hanna Viisanen, Ilida Suleymanova, Henna Tiilikainen, Zhilin Li, Tuomas O Lilius, Kert Mätlik, Jenni E Anttila, Mikko Airavaara, Li Tian, Pekka V Rauhala, Eija A Kalso
Development of tolerance is a well known pharmacological characteristic of opioids and a major clinical problem. In addition to the known neuronal mechanisms of opioid tolerance, activation of glia has emerged as a potentially significant new mechanism. We studied activation of microglia and astrocytes in morphine tolerance and opioid-induced hyperalgesia in rats using immunohistochemistry, flow cytometry and RNA sequencing in spinal- and supraspinal regions. Chronic morphine treatment that induced tolerance and hyperalgesia also increased immunoreactivity of spinal microglia in the dorsal and ventral horns...
February 6, 2018: Neuroscience
https://www.readbyqxmd.com/read/29419657/neuroinflammation-of-the-spinal-cord-and-nerve-roots-in-chronic-radicular-pain-patients
#8
Daniel Albrecht, Shihab Ahmed, Norman Kettner, Ronald Borra, Julien Cohen-Adad, Hao Deng, Timothy Houle, Arissa Opalacz, Sarah Roth, Marcos Vidal Melo, Lucy Chen, Jianren Mao, Jacob Hooker, Marco L Loggia, Yi Zhang
Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (e.g., microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain...
February 5, 2018: Pain
https://www.readbyqxmd.com/read/29416128/microglia-in-neuropathic-pain-cellular-and-molecular-mechanisms-and-therapeutic-potential
#9
REVIEW
Kazuhide Inoue, Makoto Tsuda
Acute nociceptive pain is a key defence system that enables the detection of danger signals that threaten homeostasis and survival. However, chronic pain (such as the neuropathic pain that occurs after peripheral nerve injury) is not simply a consequence of the continuity of acute nociceptive signals but rather of maladaptive nervous system function. Over recent decades, studies have provided evidence for the necessity and sufficiency of microglia for the alterations in synaptic remodelling, connectivity and network function that underlie chronic pain and have shed light on the underlying molecular and cellular mechanisms...
February 8, 2018: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29393487/effects-of-metformin-on-the-expression-of-ampk-and-stat3-in-the-spinal-dorsal-horn-of-rats-with-neuropathic-pain
#10
Anqi Ge, Shu Wang, Bei Miao, Ming Yan
Neuropathic pain (NP) is a frustrating and burdensome problem. Current treatments for NP have unendurable side effects and/or questionable efficacy, and once these therapies are stopped, the symptoms often return. Thus, novel drugs are needed to enhance the effectiveness of treatments for NP. One novel target for pain treatments is adenosine monophosphate‑activated protein kinase (AMPK), which regulates a variety of cellular processes, including protein translation, which is considered to be affected in NP...
February 1, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29378191/involvement-of-the-n-ofq-nop-system-in-rat-morphine-antinociceptive-tolerance-are-astrocytes-the-crossroad
#11
Laura Micheli, Elena Lucarini, Francesca Corti, Roberto Ciccocioppo, Girolamo Calò, Anna Rizzi, Carla Ghelardini, Lorenzo Di Cesare Mannelli
The development of tolerance to the antinociceptive effect is a main problem associated with the repeated administration of opioids. The progressively higher doses required to relieve pain reduce safety and exacerbate the side effects of classical opioid receptor agonists like morphine. Nociceptin/orphanin FQ (N/OFQ) and its NOP receptor constitute the fourth endogenous opioid system that is involved in the control of broad spectrum of biological functions, including pain transmission. Aim of this work was to evaluate the relevance of the N/OFQ-NOP system in morphine antinociceptive action and in the development of morphine tolerance in the rat...
January 26, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29351125/central-inhibition-of-granulocyte-macrophage-colony-stimulating-factor-is-analgesic-in-experimental-neuropathic-pain
#12
Louise S C Nicol, Peter Thornton, Jon P Hatcher, Colin P Glover, Carl I Webster, Matthew Burrell, Kessia Hammett, Clare A Jones, Matthew A Sleeman, Andrew Billinton, Iain Chessell
With less than 50% of patients responding to the current standard of care and poor efficacy and selectivity of current treatments, neuropathic pain continues to be an area of considerable unmet medical need. Biological therapeutics such as monoclonal antibodies (mAbs) provide better intrinsic selectivity; however, delivery to the central nervous system (CNS) remains a challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well described in inflammation-induced pain, and early-phase clinical trials evaluating its antagonism have exemplified its importance as a peripheral pain target...
January 16, 2018: Pain
https://www.readbyqxmd.com/read/29350427/role-of-microglia-in-the-spinal-cord-in-colon-to-bladder-neural-crosstalk-in-a-rat-model-of-colitis
#13
Tsuyoshi Majima, Yasuhito Funahashi, Naoki Kawamorita, Shun Takai, Yoshihisa Matsukawa, Tokunori Yamamoto, Naoki Yoshimura, Momokazu Gotoh
AIMS: We investigated whether spinal cord microglia are involved in colon-to-bladder neural crosstalk in a rat model of colitis. METHODS: Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by administering 50% trinitrobenzene sulfonic acid into the distal colon in the colitis group and the minocycline group. Minocycline, a microglial inhibitor, was continuously infused into the intrathecal space in the minocycline group...
January 19, 2018: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29349661/pkm2-is-involved-in-neuropathic-pain-by-regulating-erk-and-stat3-activation-in-rat-spinal-cord
#14
Binbin Wang, Siyuan Liu, Bingbing Fan, Xingguo Xu, Yonglin Chen, Rongxiang Lu, Zhongling Xu, Xiaojuan Liu
BACKGROUND: Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated. METHODS: Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis...
January 18, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29342105/neuroimmune-driven-neuropathic-pain-establishment-a-focus-on-gender-differences
#15
REVIEW
Vincenzo Coraggio, Francesca Guida, Serena Boccella, Mariantonietta Scafuro, Salvatore Paino, Domenico Romano, Sabatino Maione, Livio Luongo
The role of neuroinflammatory cells in the establishment of neuropathic pain has been investigated in depth in the last few years. In particular, microglia have been shown to be key players in the induction of tactile allodynia, as they release proinflammatory molecules that, in turn, sensitize nociceptive neurons within the spinal cord. However, the role of peripheral immune cells such as macrophages, infiltrating monocytes, mast cells, and T-cells has been highlighted in the last few studies, even though the data are still conflicting and need to be clarified...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29323698/xist-accelerates-neuropathic-pain-progression-through-regulation-of-mir-150-and-zeb1-in-cci-rat-models
#16
Xue-Tao Yan, Jing-Min Lu, Yu Wang, Xiao-Li Cheng, Xiang-Hu He, Wen-Zhong Zheng, Hu Chen, Yan-Lin Wang
LncRNAs are reported to participate in neuropathic pain development. LncRNA X-inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29310667/wwl70-protects-against-chronic-constriction-injury-induced-neuropathic-pain-in-mice-by-cannabinoid-receptor-independent-mechanisms
#17
Jie Wen, Melissa Jones, Mikiei Tanaka, Prabhuanand Selvaraj, Aviva J Symes, Brian Cox, Yumin Zhang
BACKGROUND: Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases. Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects...
January 8, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29276736/maternal-separation-stress-leads-to-resilience-against-neuropathic-pain-in-adulthood
#18
Julien Genty, Milène Tetsi Nomigni, Fernand Anton, Ulrike Hanesch
Early life stress (ELS) leads to a permanent reprogramming of biochemical stress response cascades that may also be relevant for the processing of chronic pain states such as neuropathy. Despite clinical evidence, little is known about ELS-related vulnerability for neuropathic pain and the possibly underlying etiology. In the framework of experimental studies aimed at investigating the respective relationships we used the established ELS model of maternal separation (MS). Rat dams and neonates were separated for 3 h/day from post-natal day 2-12...
February 2018: Neurobiology of Stress
https://www.readbyqxmd.com/read/29258553/prenatal-alcohol-exposure-is-a-risk-factor-for-adult-neuropathic-pain-via-aberrant-neuroimmune-function
#19
Joshua J Sanchez, Shahani Noor, Suzy Davies, Daniel Savage, Erin D Milligan
BACKGROUND: Clinical studies show that prenatal alcohol exposure (PAE) results in effects that persist into adulthood. Experimental animal models of moderate PAE demonstrate that young adults with PAE display potentiated sensitivity to light touch, clinically termed allodynia, following sciatic nerve chronic constriction injury (CCI) that coincides with heightened spinal glial, spinal macrophage, and peripheral immune responses. However, basal touch sensitivity and corresponding glial and leukocyte activation are unaltered...
December 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29248693/neuropathic-pain-inhibitor-rap-103-is-a-potent-inhibitor-of-microglial-ccl1-ccr8
#20
Mami Noda, Daichi Tomonaga, Kota Kitazono, Yusaku Yoshioka, Jiadai Liu, Jean-Philippe Rouseau, Richard Kinkead, Michael R Ruff, Candace B Pert
Chemokine signalling is important in neuropathic pain, with microglial cells expressing chemokine (C-C motif) receptor CCR2, CCR5 and CCR8, all playing key roles. In the previous report (Padi et al., 2012), oral administration of a short peptide, RAP-103, for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia after partial ligation of the sciatic nerve in rodents. As for the mechanism of the inhibiting effect of RAP-103, it was speculated to be due to dual blockade of CCR2 and CCR5...
December 14, 2017: Neurochemistry International
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