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Spinal nerve ligation

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https://www.readbyqxmd.com/read/28428091/characterization-of-the-effects-of-l-4-chlorokynurenine-on-nociception-in-rodents
#1
Tony L Yaksh, Robert Schwarcz, H Ralph Snodgrass
Upon systemic administration in rats, the prodrug L-4-chlorokynurenine (4-Cl-KYN) (AV-101) is rapidly absorbed, actively transported across the blood-brain barrier, and converted in astrocytes to 7-chlorokynurenic acid (7-Cl-KYNA), a potent and specific antagonist of the GlyB co-agonist site of the NMDA receptor. We examined the effects of 4-Cl-KYN in several rat models of hyperalgesia and allodynia and determined the concentrations of 4-Cl-KYN and newly produced 7-Cl-KYNA in serum, brain and spinal cord. Adult male rats were given 4-Cl-KYN (56, 167, 500 mg/kg), the NMDA receptor antagonist MK-801 (0...
April 17, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28416380/spinal-dopaminergic-involvement-in-the-antihyperalgesic-effect-of-antidepressants-in-a-rat-model-of-neuropathic-pain
#2
Mi Chen, Hajime Hoshino, Shigeru Saito, Yang Yang, Hideaki Obata
Antidepressants such as tricyclic antidepressants, and serotonin noradrenaline reuptake inhibitors are a first-line treatment for neuropathic pain. Here, we aimed to determine the involvement of the spinal dopaminergic system in the antihyperalgesic effects of antidepressants in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). The right L5 spinal nerve of male Sprague-Dawley rats was ligated under inhalation anesthesia to induce hyperalgesia. Behavioral testing was performed by measuring ipsilateral hindpaw withdrawal thresholds after intraperitoneal injection of amitriptyline, duloxetine, milnacipran, and fluoxetine...
April 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28394782/decrease-of-growth-and-differentiation-factor-10-contributes-to-neuropathic-pain-through-n-methyl-d-aspartate-receptor-activation
#3
Long Jiang, Botao Tan, Sen Li, Li Wang, Liqiang Zheng, Yuan Liu, Zaiyun Long, Yamin Wu
Neuropathic pain is a chronic disease with hallmarks such as chronic allodynia and hyperalgesia. Previous studies have shown that the transforming growth factor-β superfamily acts as a protecting factor against neuropathic pain. In the current study, we found that growth and differentiation factor 10 (GDF10), which belongs to the transforming growth factor-β superfamily, is mainly expressed in the superficial layers of spinal dorsal horn neurons and it was dramatically downregulated after spinal nerve ligation and N-methyl-D-aspartate (NMDA) intrathecal infusion...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28389721/chemokines-in-neuron-glial-cell-interaction-and-pathogenesis-of-neuropathic-pain
#4
REVIEW
Zhi-Jun Zhang, Bao-Chun Jiang, Yong-Jing Gao
Neuropathic pain resulting from damage or dysfunction of the nervous system is a highly debilitating chronic pain state and is often resistant to currently available treatments. It has become clear that neuroinflammation, mainly mediated by proinflammatory cytokines and chemokines, plays an important role in the establishment and maintenance of neuropathic pain. Chemokines were originally identified as regulators of peripheral immune cell trafficking and were also expressed in neurons and glial cells in the central nervous system...
April 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28361271/the-development-of-translational-biomarkers-as-a-tool-for-improving-the-understanding-diagnosis-and-treatment-of-chronic-neuropathic-pain
#5
David A Buckley, Elaine M Jennings, Nikita N Burke, Michelle Roche, Veronica McInerney, Jonathan D Wren, David P Finn, Patrick C McHugh
Chronic neuropathic pain (CNP) is one of the most significant unmet clinical needs in modern medicine. Alongside the lack of effective treatments, there is a great deficit in the availability of objective diagnostic methods to reliably facilitate an accurate diagnosis. We therefore aimed to determine the feasibility of a simple diagnostic test by analysing differentially expressed genes in the blood of patients diagnosed with CNP of the lower back and compared to healthy human controls. Refinement of microarray expression data was performed using correlation analysis with 3900 human 2-colour microarray experiments...
March 30, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28346321/growth-arrest-and-dna-damage-inducible-protein-45%C3%AE-mediated-dna-demethylation-of-voltage-dependent-t-type-calcium-channel-3-2-subunit-enhances-neuropathic-allodynia-after-nerve-injury-in-rats
#6
Cheng-Yuan Lai, Ming-Chun Hsieh, Yu-Cheng Ho, An-Sheng Lee, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
BACKGROUND: Growth arrest and DNA-damage-inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage-inducible protein 45β-dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear. METHODS: Adult male Sprague-Dawley rats (654 out of 659) received a spinal nerve ligation or a sham operation with or without intrathecal application of one of the following: growth arrest and DNA-damage-inducible protein 45β messenger RNA-targeted small interfering RNA, lentiviral vector expressing growth arrest and DNA-damage-inducible protein 45β, Ro 25-6981 (an NR2B-bearing N-methyl-D-aspartate receptor antagonist), or KN-93 (a calmodulin-dependent protein kinase II antagonist) were used for behavioral measurements, Western blotting, immunofluorescence, dot blots, detection of unmodified cytosine enrichment at cytosine-phosphate-guanine site, chromatin immunoprecipitation quantitative polymerase chain reaction analysis, and slice recordings...
March 27, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28341636/relief-from-neuropathic-pain-by-blocking-of-the-platelet-activating-factor-pain-loop
#7
Hideo Shindou, Seiji Shiraishi, Suzumi M Tokuoka, Yoshikazu Takahashi, Takeshi Harayama, Takaya Abe, Kana Bando, Kanako Miyano, Yoshihiro Kita, Yasuhito Uezono, Takao Shimizu
Neuropathic pain resulting from peripheral neuronal damage is largely resistant to treatment with currently available analgesic drugs. Recently, ATP, lysophosphatidic acid, and platelet-activating factor (PAF) have been reported to play important inductive roles in neuropathic pain. In the present study, we found that pain-like behaviors resulting from partial sciatic nerve ligation (PSL) were largely attenuated by deficiency of lysophosphatidylcholine acyltransferase (LPCAT)2, which is one of the PAF biosynthetic enzymes...
March 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28330877/k-channel-modulatory-subunits-kchip-and-dpp-participate-in-kv4-mediated-mechanical-pain-control
#8
Yen-Ling Kuo, Jen-Kun Cheng, Wen-Hsien Hou, Yu-Cheng Chang, Po-Hao Du, Jhao-Jun Jian, Ruey-Horng Rau, Jung-Hui Yang, Cheng-Chang Lien, Meei-Ling Tsaur
The K(+) channel pore-forming subunit Kv4.3 is expressed in a subset of nonpeptidergic nociceptors within the dorsal root ganglion (DRG), and knockdown of Kv4.3 selectively induces mechanical hypersensitivity, a major symptom of neuropathic pain. K(+) channel modulatory subunits KChIP1, KChIP2, and DPP10 are coexpressed in Kv4.3(+) DRG neurons, but whether they participate in Kv4.3-mediated pain control is unknown. Here, we show the existence of a Kv4.3/KChIP1/KChIP2/DPP10 complex (abbreviated as the Kv4 complex) in the endoplasmic reticulum and cell surface of DRG neurons...
April 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28323403/discovery-of-potent-antiallodynic-agents-for-neuropathic-pain-targeting-p2x3-receptors
#9
Young-Hwan Jung, Yong-Chul Kim, Yeo Ok Kim, Hai Lin, Joong-Heui Cho, Jin-Hee Park, So-Deok Lee, Jinsu Bae, Koon Mook Kang, Yoon Gyoon Kim, Ae Nim Pae, Hyojin Ko, Chul-Seung Park, Myung Ha Yoon
Antagonism of the P2X3 receptor is one of the potential therapeutic strategies for the management of neuropathic pain because P2X3 receptors are predominantly localized on small to medium diameter C- and Aδ-fiber primary afferent neurons, which are related to the pain-sensing system. In this study, 5-hydroxy pyridine derivatives were designed, synthesized, and evaluated for their in vitro biological activities by two-electrode voltage clamp assay at hP2X3 receptors. Among the novel hP2X3 receptor antagonists, intrathecal treatment of compound 29 showed parallel efficacy with pregabalin (calcium channel modulator) and higher efficacy than AF353 (P2X3 receptor antagonist) in the evaluation of its antiallodynic effects in spinal nerve ligation rats...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28302538/protective-effects-of-garcinol-against-neuropathic-pain-evidence-from-in-vivo-and-in-vitro-studies
#10
Yi-Wei Wang, Xiang Zhang, Chun-Long Chen, Qing-Zhen Liu, Jia-Wen Xu, Qing-Qing Qian, Wei-Yan Li, Yan-Ning Qian
Neuroinflammatory processes have a vital role in the pathogenesis of neuropathic pain. Garcinol, harvested from Garcinia indica, is known to exert potent anti-inflammatory properties. Recent studies have indicated that Garcinol may inhibit activation of nuclear factor-κB (NF-κB) by inhibiting NF-κB/p65 acetylation. These findings prompted us to evaluate the protective effects of Garcinol in the lumbar fifth spinal nerve ligation (SNL)-induced rat model of neuropathic pain and Lipopolysaccharide(LPS)-stimulated primary cultured microglia...
March 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28300618/the-novel-and-potent-anti-depressive-action-of-triptolide-and-its-influences-on-hippocampal-neuroinflammation-in-a-rat-model-of-depression-comorbidity-of-chronic-pain
#11
Xiaofan Hu, Yulin Dong, Xiaohang Jin, Chunkui Zhang, Ting Zhang, Jie Zhao, Juan Shi, Jinlian Li
Chronic pain and depression frequently coexist in clinical setting, and current clinical treatments for this comorbidity have shown limited efficacy. Triptolide (T10), an active component of Tripterygium wilfordii Hook F., has been demonstrated to exert strong analgesic activities in experimental pain models, but whether it possesses anti-depressive actions remains unknown. Using a depression comorbidity of chronic pain rat model induced by spinal nerve ligation (SNL), we investigated the potency of T10 for the treatment of comorbid depression in comparison with a widely used antidepressant, fluoxetine (FLX)...
March 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28277328/isobolographic-analysis-of-drug-combinations-with-intrathecal-brl52537-%C3%AE%C2%BA-opioid-agonist-pregabalin-calcium-channel-modulator-af-353-p2x3-receptor-antagonist-and-a804598-p2x7-receptor-antagonist-in-neuropathic-rats
#12
Young-Hwan Jung, Yeo Ok Kim, Jung Hyun Han, Yong-Chul Kim, Myung Ha Yoon
BACKGROUND: Neuropathic pain should be treated with drug combinations exhibiting multiple analgesic mechanisms of action because the mechanism of neuropathic pain involves multiple physiological causes and is mediated by multiple pathways. In this study, we defined the pharmacological interaction of BRL52537 (κ-opioid agonist), pregabalin (calcium channel modulator), AF 353 (P2X3 receptor antagonist), and A804598 (P2X7 receptor antagonist). METHODS: Animal models of neuropathic pain were established by spinal nerve ligation (SNL) in male Sprague-Dawley rats, and responses to the mechanical stimulation using von Frey filaments were measured...
March 8, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28257897/ezh2-regulates-spinal-neuroinflammation-in-rats-with-neuropathic-pain
#13
Ruchi Yadav, Han-Rong Weng
Alteration in gene expression along the pain signaling pathway is a key mechanism contributing to the genesis of neuropathic pain. Accumulating studies have shown that epigenetic regulation plays a crucial role in nociceptive process in the spinal dorsal horn. In this present study, we investigated the role of enhancer of zeste homolog-2 (EZH2), a subunit of the polycomb repressive complex 2, in the spinal dorsal horn in the genesis of neuropathic pain in rats induced by partial sciatic nerve ligation. EZH2 is a histone methyltransferase, which catalyzes the methylation of histone H3 on K27 (H3K27), resulting in gene silencing...
May 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28230181/dezocine-exhibits-antihypersensitivity-activities-in-neuropathy-through-spinal-%C3%AE-opioid-receptor-activation-and-norepinephrine-reuptake-inhibition
#14
Yong-Xiang Wang, Xiao-Fang Mao, Teng-Fei Li, Nian Gong, Ma-Zhong Zhang
Dezocine is the number one opioid painkiller prescribed and sold in China, occupying 44% of the nation's opioid analgesics market today and far ahead of the gold-standard morphine. We discovered the mechanisms underlying dezocine antihypersensitivity activity and assessed their implications to antihypersensitivity tolerance. Dezocine, given subcutaneously in spinal nerve-ligated neuropathic rats, time- and dose-dependently produced mechanical antiallodynia and thermal antihyperalgesia, significantly increased ipsilateral spinal norepinephrine and serotonin levels, and induced less antiallodynic tolerance than morphine...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197545/active-nerve-regeneration-with-failed-target-reinnervation-drives-persistent-neuropathic-pain
#15
Wenrui Xie, Judith A Strong, Jun-Ming Zhang
Peripheral nerves can regenerate and, when injured, may cause neuropathic pain. We propose that the active regeneration process plays a pivotal role in the maintenance of neuropathic pain. In one commonly used rodent neuropathic pain model, pronounced pain behaviors follow ligation and cutting of the L5 spinal nerve. We found that the injured nerve regenerates into the sciatic nerve and functionally reinnervates target tissues: the regenerated nerve conducts electrical signals, mechanical responses, and tracers between the leg/hindpaw and axotomized sensory ganglion...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28195183/interleukin-1%C3%AE-pre-treated-bone-marrow-stromal-cells-alleviate-neuropathic-pain-through-ccl7-mediated-inhibition-of-microglial-activation-in-the-spinal-cord
#16
Jian Li, Guoying Deng, Haowei Wang, Mei Yang, Rui Yang, Xiangnan Li, Xiaoping Zhang, Hongbin Yuan
Although neuropathic pain is one of the most intractable diseases, recent studies indicate that systemic or local injection of bone marrow stromal cells (BMSCs) decreases pro-inflammatory cytokines release and alleviates neuropathic pain. However, it is still not clear whether pre-treated BMSCs have a strong anti-inflammatory and/or analgesia effect. Using the spinal nerve ligation model of neuropathic pain, IL-1β pre-treated BMSCs (IL-1β-BMSCs) were injected into rats followed by SNL in order to determine possible effects...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28177520/broad-spectrum-efficacy-with-ly2969822-an-oral-prodrug-of-metabotropic-glutamate-2-3-receptor-agonist-ly2934747-in-rodent-pain-models
#17
Michael P Johnson, Mark A Muhlhauser, Eric S Nisenbaum, Rosa M A Simmons, Beth M Forster, Kelly L Knopp, Lijuan Yang, Denise Morrow, Dominic L Li, Jeffrey D Kennedy, Steven Swanson, James A Monn
BACKGROUND AND PURPOSE: A body of evidence suggests activation of metabotropic glutamate 2/3 (mGlu2/3 ) receptors would be an effective analgesic in chronic pain conditions. Thus, the analgesic properties of a novel mGlu2/3 receptor agonist prodrug were investigated. EXPERIMENTAL APPROACH: After oral absorption, the prodrug LY2969822 rapidly converts to the brain penetrant, potent and subtype-selective mGlu2/3 receptor agonist LY2934747. Behavioural assessments of allodynia, hyperalgesia and nocifensive behaviours were determined in preclinical pain models after administration of LY2969822 0...
May 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28158164/rapid-and-delayed-effects-of-pulsed-radiofrequency-on-neuropathic-pain-electrophysiological-molecular-and-behavioral-evidence-supporting-long-term-depression
#18
Ren-Yu Huang, Chia-Chi Liao, Shih-Ying Tsai, Chen-Tung Yen, Chii-Wann Lin, Tsung-Chi Chen, Wei-Tso Lin, Chi-Heng Chang, Yeong-Ray Wen
BACKGROUND: Pulsed radiofrequency (PRF) has been widely employed for ameliorating clinical neuropathic pain. How PRF alters electrophysiological transmission and modulates biomolecular functions in neural tissues has yet to be clarified. We previously demonstrated that an early application of low-voltage bipolar PRF adjacent to the dorsal root ganglion (DRG) reduced acute neuropathic pain in animals. By contrast, the present study investigated how PRF alters postsynaptic sensitization to produce early and delayed effects on neuropathic pain...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28155010/chemokine-cxcl13-activates-p38-mapk-in-the-trigeminal-ganglion-after-infraorbital-nerve-injury
#19
Qian Zhang, Ming-Di Zhu, De-Li Cao, Xue-Qiang Bai, Yong-Jing Gao, Xiao-Bo Wu
Recent data demonstrated that chemokine CXCL13 mediates neuroinflammation and contributes to the maintenance of neuropathic pain after nerve injury in the spinal cord. Pro-nociceptive chemokines activate mitogen-activated protein kinases (MAPKs) which are potential signaling pathways contributing to the nociceptive behavior in inflammatory or neuropathic pain. However, whether activation of p38 and JNK MAPK signaling pathway in the trigeminal ganglion (TG) are involved in CXCL13 and its receptor CXCR5-mediated orofacial pain has not yet been clarified...
February 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28145509/serum-protein-changes-in-a-rat-model-of-chronic-pain-show-a-correlation-between-animal-and-humans
#20
Elisa Bellei, Antonietta Vilella, Emanuela Monari, Stefania Bergamini, Aldo Tomasi, Aurora Cuoghi, Simona Guerzoni, Letizia Manca, Michele Zoli, Luigi Alberto Pini
In previous works we showed the overexpression of some proteins in biological fluids from patients suffering chronic pain. In this proteomic study we analysed serum from a rat model of neuropathic pain obtained by the chronic constriction injury (CCI) of sciatic nerve, at two time intervals, 2 and 5 weeks after the insult, to find proteins involved in the expression or mediation of pain. Sham-operated and CCI rats were treated with saline or indomethacin. Two weeks after ligation, we identified three serum proteins overexpressed in CCI rats, two of which, alpha-1-macroglobulin and vitamin D-binding protein (VDBP), remained increased 5 weeks post-surgery; at this time interval, we found increased levels of further proteins, namely apolipoprotein A-I (APOA1), apolipoprotein E (APOE), prostaglandin-H2 D-isomerase (PTGDS) and transthyretin (TTR), that overlap the overexpressed proteins found in humans...
February 1, 2017: Scientific Reports
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