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https://www.readbyqxmd.com/read/28729057/neuropathic-pain-alleviating-effects-of-pyrazole-conjugated-arylsulfonamides-as-5-ht6-receptor-antagonists
#1
Jin Ri Hong, Hyunah Choo, Ghilsoo Nam
A novel series of arylsulfonylaminomethyl-3-(1-phenyl-5-isopropyl)pyrazoles was evaluated for serotonin receptor subtype 6 (5-HT6R) antagonistic effects in vitro. We also investigated their neuropathic pain-alleviating effects in vivo using a rat spinal nerve ligation (SNL) model. Bicyclic aromatic sulfonamino groups, such as naphthalene and quinolin-substituted derivatives, showed good 5-HT6 inhibitory activity in vitro. Among them, selected compounds, 12 and 13, having 8-quinoylsulfonamino groups, showed potent neuropathic pain-alleviating effects in the rat model...
July 11, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28722336/evidence-for-the-modulation-of-nociception-in-mice-by-central-mast-cells
#2
C L Kissel, K J Kovács, A A Larson
BACKGROUND: Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. METHODS: We examined the central effect of two hyperalgesic compounds that induce mast cell degranulation and of stabilized mast cells using cromolyn. RESULTS: Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1-17) (opioid compound) each correlated with the per cent of thalamic mast cells that were degranulated...
July 19, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28721088/forced-exercise-attenuates-neuropathic-pain-in-chronic-constriction-injury-of-male-rat-an-investigation-of-oxidative-stress-and-inflammation
#3
Hossein Ali Safakhah, Nasroallah Moradi Kor, Atiyeh Bazargani, Ahmad Reza Bandegi, Hamid Gholami Pourbadie, Baharak Khoshkholgh-Sima, Ali Ghanbari
BACKGROUND AND OBJECTIVE: Initial peripheral/central nerve injuries, such as chronic constriction injury (CCI)/spinal cord injury, are often compounded by secondary mechanisms, including inflammation and oxidative stress, which may lead to chronic neuropathic pain characterized by hyperalgesia or allodynia. On the other hand, exercise as a behavioral and non-pharmacological treatment has been shown to alleviate chronic neuropathic pain. Therefore, this study was conducted to examine whether or not exercise reduces neuropathic pain through modifying oxidative stress and inflammation in chronic constriction injury of the sciatic nerve...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28719859/-curcumin-loaded-poly-d-l-lactide-co-glycolide-nanovesicles-induce-antinociceptive-effects-and-reduce-pronociceptive-cytokine-and-bdnf-release-in-spinal-cord-after-acute-administration-in-mice
#4
Stefano Pieretti, Amalendu P Ranjan, Amalia Di Giannuario, Anindita Mukerjee, Francesca Marzoli, Rita Di Giovannandrea, Jamboor K Vishwanatha
Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28718992/melatonin-impedes-tet1-dependent-mglur5-promoter-demethylation-to-relieve-pain
#5
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Dylan Chou, Hsueh-Hsiao Wang, Gin-Den Chen, Tzer-Bin Lin, Hsien-Yu Peng
Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity...
July 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28708760/reactive-oxygen-species-affect-spinal-cell-type-specific-synaptic-plasticity-in-a-model-of-neuropathic-pain
#6
Alice Bittar, Jaebeom Jun, Jun-Ho La, Jigong Wang, Joong Woo Leem, Jin Mo Chung
Spinal synaptic plasticity is believed to drive central sensitization that underlies the persistent nature of neuropathic pain. Our recent data showed that synaptic plasticity in the dorsal horn is cell type-specific: intense afferent stimulation produced long-term potentiation (LTP) in excitatory spinothalamic tract neurons (STTn), whereas it produced long-term depression (LTD) in inhibitory GABAergic interneurons (GABAn). In addition, reactive oxygen species (ROS) were shown to be involved in LTP in STTn (STTn-LTP) as well as in LTD in GABAn (GABAn-LTD)...
July 11, 2017: Pain
https://www.readbyqxmd.com/read/28680400/a-novel-small-molecule-gdnf-receptor-ret-agonist-bt13-promotes-neurite-growth-from-sensory-neurons-in-vitro-and-attenuates-experimental-neuropathy-in-the-rat
#7
Yulia A Sidorova, Maxim M Bespalov, Agnes W Wong, Oleg Kambur, Viljami Jokinen, Tuomas O Lilius, Ilida Suleymanova, Gunnar Karelson, Pekka V Rauhala, Mati Karelson, Peregrine B Osborne, Janet R Keast, Eija A Kalso, Mart Saarma
Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clinical therapies are needed as current treatments typically provide only symptomatic relief; show varying clinical efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage. Two candidate targets are glial cell line-derived neurotrophic factor (GDNF) and artemin (ARTN), as these GDNF family ligands (GFLs) show efficacy in animal models of neuropathic pain (Boucher et al...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28656207/expression-of-granulocyte-colony-stimulating-factor-3-receptor-in-the-spinal-dorsal-horn-following-spinal-nerve-ligation-induced-neuropathic-pain
#8
Enji Zhang, Sunyeul Lee, Min-Hee Yi, Yongshan Nan, Yinshi Xu, Nara Shin, Youngkwon Ko, Young Ho Lee, Wonhyung Lee, Dong Woon Kim
In previous studies that have profiled gene expression in patients with complex regional pain syndrome (CRPS), the expression of granulocyte colony-stimulating factor 3 receptor (G‑CSFR) was elevated, as were a number of pain‑associated genes. The present study determined the expression of G‑CSFR and the mechanisms by which it may affect hypersensitivity, focusing on the signal transducer and activator of transcription 3 (STAT3)/transient receptor potential cation channel subfamily V 1 (TRPV1) signaling pathway in particular, which is an important mediator of pain...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28652182/ulinastatin-attenuates-neuropathic-pain-via-the-atp-p2y2-receptor-pathway-in-rat-models
#9
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/28626095/-role-of-the-autophagy-in-the-treatment-of-neuropathic-pain-with-pulsed-radiofrequency
#10
Lin Yang, Liang Guo, Junmei Xu, Yaping Wang, Dingquan Zou, Xinghua Jiang
To detect the effect of pulse radiofrequency (PRF) treatment on the neuropathic pain established by L5-spinal nerve ligation (SNL) on rats, and to investigate if PRF treatment would affect the expression of autophagy related protein LC3 and autophagy related receptor P62 at the dorsal horn.
 Methods: A total of 36 male Sprague-Dawley rats were randomly divided into 3 groups: a Sham group, a SNL group, and a SNL+PRF group. The 50% paw withdrawal mechanical threshold (PWMT) was detected at 1 day before and 1, 3, 7, 14 and 28 days post-operation by using Von-Frey filaments...
May 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28614825/effect-of-ceftiofur-on-hyperalgesia-and-allodynia-in-a-rat-neuropathic-pain-model-the-role-of-immune-processes
#11
Aytül Önal, Deniz Coşkunsever, Fatma Gül Çelenk, Recep Selim Şentürk, Selvi Nalbant, Sibel Ülker Göksel
OBJECTIVE: Inflammatory and immune mechanisms play important roles in the pathogenesis of neuropathic pain. Ceftiofur, a third-generation cephalosporin, has anti-inflammatory effects by inhibiting tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor (NF)-κB, and mitogen-activated protein kinase (MAPK) signaling. This study aimed to investigate the effect of ceftiofur on hyperalgesia and allodynia in neuropathic rats and to define the possible contribution of immune mechanisms to this effect...
June 15, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28612120/anti-allodynic-action-of-the-disease-modifying-anti-rheumatic-drug-iguratimod-in-a-rat-model-of-neuropathic-pain
#12
K Morimoto, A Miura, Keiichi Tanaka
OBJECTIVE: Patients with rheumatoid arthritis experience nociceptive as well as neuropathic pain. The effect of iguratimod (IGU), a disease-modifying anti-rheumatic drug, on neuropathic pain in a rat model of chronic constriction injury (CCI) was examined in this study. METHODS: CCI was induced by making four ligations on the left sciatic nerve. Rats with stable signs of static allodynia were selected 2 weeks after the surgery and drug treatments were started (day 0)...
June 13, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28590304/antinociceptive-effect-of-epicatechin-in-inflammatory-and-neuropathic-pain-in-rats
#13
Geovanna N Quiñonez-Bastidas, Jorge B Pineda-Farias, Francisco J Flores-Murrieta, Juan Rodríguez-Silverio, Juan G Reyes-García, Beatriz Godínez-Chaparro, Vinicio Granados-Soto, Héctor I Rocha-González
The aim of this study was to investigate the antinociceptive potential of (-)-epicatechin and the possible mechanisms of action involved in its antinociceptive effect. The carrageenan and formalin tests were used as inflammatory pain models. A plethysmometer was used to measure inflammation and L5/L6 spinal nerve ligation as a neuropathic pain model. Oral (-)-epicatechin reduced carrageenan-induced inflammation and nociception by about 59 and 73%, respectively, and reduced formalin- induced and nerve injury-induced nociception by about 86 and 43%, respectively...
June 5, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28579944/impaired-spinal-glucocorticoid-receptor-signaling-contributes-to-the-attenuating-effect-of-depression-on-mechanical-allodynia-and-thermal-hyperalgesia-in-rats-with-neuropathic-pain
#14
Xiao Wei, Yuqi Sun, Fei Luo
Although depression-induced altered pain perception has been described in several laboratory and clinical studies, its neurobiological mechanism in the central nervous system (CNS), particularly in the spinal dorsal horn, remains unclear. Therefore, in this study, we aimed to clarify whether nociceptive sensitivity of neuropathic pain is altered in the olfactory bulbectomy (OB) model of depression and whether glucocorticoid receptor (GR), which is involved in the etio-pathologic mechanisms of both major depression and neuropathic pain, contributes to these processes in the spinal dorsal horn of male Sprague-Dawley rats...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28576833/spinal-cord-stimulation-reduces-ventricular-arrhythmias-during-acute-ischemia-by-attenuation-of-regional-myocardial-excitability
#15
Kimberly Howard-Quijano, Tatsuo Takamiya, Erica A Dale, Jasmine Kipke, Yukiko Kubo, Tristan Grogan, Andyshea Afyouni, Kalyanam Shivkumar, Aman Mahajan
BACKGROUND: Myocardial ischemia creates autonomic nervous system imbalance and can trigger cardiac arrhythmias. We hypothesize that neuromodulation by spinal cord stimulation (SCS) will attenuate local cardiac sympathoexcitation from ischemia-induced increases in afferent signaling, reduce ventricular arrhythmias, and improve myocardial function during acute ischemia. METHODS: Yorkshire pigs (n=20) were randomized to SCS (50 Hz at 200μsec duration, current 90% motor threshold) or Sham for 30 min prior to ischemia...
June 2, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28565999/ryk-receptors-on-unmyelinated-nerve-fibers-mediate-excitatory-synaptic-transmission-and-ccl2-release-during-neuropathic-pain-induced-by-peripheral-nerve-injury
#16
Qing Ou Yang, Wen-Jing Yang, Jian Li, Fang-Ting Liu, Hongbin Yuan, Yue-Ping Ou Yang
Background Neuropathic pain is a major pathology of the central nervous system associated with neuroinflammation. Ryk (receptor-like tyrosine kinase) receptors act as repulsive axon-guidance molecules during development of central nervous system and neural injury. Increasing evidence suggests the potential involvement of Wnt/Ryk (wingless and Int) signaling in the pathogenesis of neuropathic pain. However, its underlying mechanism remains unknown. Results The expression and location of Ryk receptor as well as its ligand Wnt1 were detected by qPCR, Western blot, and immunohistochemistry...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28560010/hyperbaric-oxygen-treatment-attenuates-neuropathic-pain-by-elevating-autophagy-flux-via-inhibiting-mtor-pathway
#17
Yong-Da Liu, Zhi-Bin Wang, Guang Han, Ping Zhao
Peripheral neuropathic pain is a complex disease, and treated based on underlying diseases. Emerging evidences suggest that hyperbaric oxygen alleviates neuropathic pain. However, its cellular and molecular mechanism on pain relief is unknown. We hypothesize that hyperbaric oxygen alleviates neuropathic pain via activating autophagy flux and inhibiting mTOR pathway. Hyperbaric oxygen effectively inhibited nerve injury induced autophagy impairment and mTOR pathway activation in a rat spinal nerve ligation (SNL) model...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28535568/tianeptine-reduces-mechanical-allodynia-in-spinal-nerve-ligated-and-chemotherapy-induced-neuropathic-mice
#18
Seong Min Han, Young Hoon Kim, Hyeon Uk Jo, Jung Ah Kwak, Hue Jung Park
BACKGROUND: Spinal nerve-ligated neuropathy and chemotherapy-induced neuropathy produce a persistent tactile allodynia in mice. Tianeptine is an antidepressant that exhibits structural similarities to tricyclic antidepressants but has distinct neurochemical properties. OBJECTIVE: Here we examined the effects of intraperitoneal (i.p.) tianeptine on allodynia in spinal nerve-ligated and chemotherapy-induced neuropathic mice. STUDY DESIGN: A randomized, experimental trial...
May 2017: Pain Physician
https://www.readbyqxmd.com/read/28534262/inflammatory-changes-in-paravertebral-sympathetic-ganglia-in-two-rat-pain-models
#19
Ai-Ling Li, Jing-Dong Zhang, Wenrui Xie, Judith A Strong, Jun-Ming Zhang
Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy...
May 22, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28533177/immunohistochemical-comparison-of-astrocytic-mglur5-upregulation-in-infraorbital-nerve-versus-sciatic-nerve-ligated-rat
#20
Benoit Michot, Ronald Deumens, Emmanuel Hermans
The differential pharmacological responsiveness of cephalic and extra-cephalic neuropathic pain has been proposed to relate to distinct mechanisms that may involve neuroinflammatory reactions mediated by glial cells. Astrocytes are particularly important for neuronal sensitization in neuropathic pain, in part through modulation of glutamatergic transmission. Because the metabotropic glutamate receptor 5 (mGluR5) is involved in the astrocytic regulation of the glutamatergic system, we investigated modifications of its expression in models of cephalic versus extra-cephalic neuropathic pain...
July 13, 2017: Neuroscience Letters
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