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[PMID]:29244816
[Au] Autor:Avila-Martin G; Mata-Roig M; Galán-Arriero I; Taylor JS; Busquets X; Escribá PV
[Ad] Endereço:Hospital Nacional de Parapléjicos, Toledo, Spain.
[Ti] Título:Treatment with albumin-hydroxyoleic acid complex restores sensorimotor function in rats with spinal cord injury: Efficacy and gene expression regulation.
[So] Source:PLoS One;12(12):e0189151, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sensorimotor dysfunction following incomplete spinal cord injury (SCI) is often characterized by paralysis, spasticity and pain. Previously, we showed that intrathecal (i.t.) administration of the albumin-oleic acid (A-OA) complex in rats with SCI produced partial improvement of these symptoms and that oral 2-hydroxyoleic acid (HOA, a non-hydrolyzable OA analogue), was efficacious in the modulation and treatment of nociception and pain-related anxiety, respectively. Here we observed that intrathecal treatment with the complex albumin-HOA (A-HOA) every 3 days following T9 spinal contusion injury improved locomotor function assessed with the Rotarod and inhibited TA noxious reflex activity in Wistar rats. To investigate the mechanism of action of A-HOA, microarray analysis was carried out in the spinal cord lesion area. Representative genes involved in pain and neuroregeneration were selected to validate the changes observed in the microarray analysis by quantitative real-time RT-PCR. Comparison of the expression between healthy rats, SCI rats, and SCI treated with A-HOA rats revealed relevant changes in the expression of genes associated with neuronal morphogenesis and growth, neuronal survival, pain and inflammation. Thus, treatment with A-HOA not only induced a significant overexpression of growth and differentiation factor 10 (GDF10), tenascin C (TNC), aspirin (ASPN) and sushi-repeat-containing X-linked 2 (SRPX2), but also a significant reduction in the expression of prostaglandin E synthase (PTGES) and phospholipases A1 and A2 (PLA1/2). Currently, SCI has very important unmet clinical needs. A-HOA downregulated genes involved with inflammation and upregulated genes involved in neuronal growth, and may serve to promote recovery of function after experimental SCI.
[Mh] Termos MeSH primário: Albuminas/farmacologia
Ácidos Oleicos/farmacologia
Dor/prevenção & controle
Paralisia/tratamento farmacológico
Recuperação de Função Fisiológica/efeitos dos fármacos
Traumatismos da Medula Espinal/tratamento farmacológico
[Mh] Termos MeSH secundário: Albuminas/química
Animais
Esquema de Medicação
Proteínas da Matriz Extracelular/agonistas
Proteínas da Matriz Extracelular/genética
Proteínas da Matriz Extracelular/metabolismo
Regulação da Expressão Gênica
Fator 10 de Diferenciação de Crescimento/agonistas
Fator 10 de Diferenciação de Crescimento/genética
Fator 10 de Diferenciação de Crescimento/metabolismo
Injeções Espinhais
Locomoção/efeitos dos fármacos
Locomoção/fisiologia
Masculino
Proteínas do Tecido Nervoso/agonistas
Proteínas do Tecido Nervoso/genética
Proteínas do Tecido Nervoso/metabolismo
Nociceptividade/efeitos dos fármacos
Ácidos Oleicos/química
Dor/genética
Dor/metabolismo
Dor/patologia
Paralisia/genética
Paralisia/metabolismo
Paralisia/patologia
Fosfolipases/antagonistas & inibidores
Fosfolipases/genética
Fosfolipases/metabolismo
Prostaglandina-E Sintases/antagonistas & inibidores
Prostaglandina-E Sintases/genética
Prostaglandina-E Sintases/metabolismo
Ratos
Ratos Wistar
Recuperação de Função Fisiológica/fisiologia
Teste de Desempenho do Rota-Rod
Medula Espinal/efeitos dos fármacos
Medula Espinal/metabolismo
Medula Espinal/patologia
Traumatismos da Medula Espinal/genética
Traumatismos da Medula Espinal/metabolismo
Traumatismos da Medula Espinal/patologia
Tenascina/agonistas
Tenascina/genética
Tenascina/metabolismo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-hydroxyoleic acid); 0 (Albumins); 0 (Extracellular Matrix Proteins); 0 (Gdf10 protein, rat); 0 (Growth Differentiation Factor 10); 0 (Nerve Tissue Proteins); 0 (Oleic Acids); 0 (Tenascin); 0 (asporin protein, rat); EC 3.1.- (Phospholipases); EC 5.3.99.3 (Prostaglandin-E Synthases); EC 5.3.99.3 (Ptges protein, rat)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189151


  2 / 1706 MEDLINE  
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[PMID]:28450396
[Au] Autor:Lei W; Mullen N; McCarthy S; Brann C; Richard P; Cormier J; Edwards K; Bilsky EJ; Streicher JM
[Ad] Endereço:From the Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona 85724.
[Ti] Título:Heat-shock protein 90 (Hsp90) promotes opioid-induced anti-nociception by an ERK mitogen-activated protein kinase (MAPK) mechanism in mouse brain.
[So] Source:J Biol Chem;292(25):10414-10428, 2017 06 23.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent advances in developing opioid treatments for pain with reduced side effects have focused on the signaling cascades of the µ-opioid receptor (MOR). However, few such signaling targets have been identified for exploitation. To address this need, we explored the role of heat-shock protein 90 (Hsp90) in opioid-induced MOR signaling and pain, which has only been studied in four previous articles. First, in four cell models of MOR signaling, we found that Hsp90 inhibition for 24 h with the inhibitor 17- -allylamino-17-demethoxygeldanamycin (17-AAG) had different effects on protein expression and opioid signaling in each line, suggesting that cell models may not be reliable for predicting pharmacology with this protein. We thus developed an model using CD-1 mice with an intracerebroventricular injection of 17-AAG for 24 h. We found that Hsp90 inhibition strongly blocked morphine-induced anti-nociception in models of post-surgical and HIV neuropathic pain but only slightly blocked anti-nociception in a naive tail-flick model, while enhancing morphine-induced precipitated withdrawal. Seeking a mechanism for these changes, we found that Hsp90 inhibition blocks ERK MAPK activation in the periaqueductal gray and caudal brain stem. We tested these signaling changes by inhibiting ERK in the above-mentioned pain models and found that ERK inhibition could account for all of the changes in anti-nociception induced by Hsp90 inhibition. Taken together, these findings suggest that Hsp90 promotes opioid-induced anti-nociception by an ERK mechanism in mouse brain and that Hsp90 could be a future target for improving the therapeutic index of opioid drugs.
[Mh] Termos MeSH primário: Analgésicos Opioides/farmacologia
Benzoquinonas/farmacologia
Tronco Encefálico/metabolismo
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Proteínas de Choque Térmico HSP90/metabolismo
Lactamas Macrocíclicas/farmacologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Nociceptividade/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Tronco Encefálico/patologia
Células CHO
Cricetinae
Cricetulus
Células HEK293
Seres Humanos
Masculino
Camundongos
Neuralgia/tratamento farmacológico
Neuralgia/metabolismo
Neuralgia/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Benzoquinones); 0 (HSP90 Heat-Shock Proteins); 0 (Lactams, Macrocyclic); 4GY0AVT3L4 (tanespimycin); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.769489


  3 / 1706 MEDLINE  
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[PMID]:29184198
[Au] Autor:Arenas OM; Zaharieva EE; Para A; Vásquez-Doorman C; Petersen CP; Gallio M
[Ad] Endereço:Department of Neurobiology, Northwestern University, Evanston, IL, USA.
[Ti] Título:Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for animal nociception.
[So] Source:Nat Neurosci;20(12):1686-1693, 2017 Dec.
[Is] ISSN:1546-1726
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea and that the conserved ion channel TRPA1 is required for these responses. TRPA1-mutant Drosophila flies are also defective in noxious-heat responses. We find that either planarian or human TRPA1 can restore noxious-heat avoidance to TRPA1-mutant Drosophila, although neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H O and reactive oxygen species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago.
[Mh] Termos MeSH primário: Nociceptividade/fisiologia
Planárias/fisiologia
Espécies Reativas de Oxigênio/farmacologia
Canal de Cátion TRPA1/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Aprendizagem da Esquiva/efeitos dos fármacos
Comportamento Animal/efeitos dos fármacos
Drosophila
Proteínas de Drosophila/genética
Peróxido de Hidrogênio/farmacologia
Nociceptividade/efeitos dos fármacos
Técnicas de Patch-Clamp
Interferência de RNA
Canal de Cátion TRPA1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (Reactive Oxygen Species); 0 (TRPA1 Cation Channel); 0 (TRPA1 protein, human); 0 (TrpA1 protein, Drosophila); BBX060AN9V (Hydrogen Peroxide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1038/s41593-017-0005-0


  4 / 1706 MEDLINE  
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[PMID]:27776498
[Au] Autor:Ozawa J; Kaneguchi A; Tanaka R; Kito N; Moriyama H
[Ad] Endereço:Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose- Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, 739-2695, Japan. j-ozawa@hs.hirokoku-u.ac.jp.
[Ti] Título:Cyclooxygenase-2 inhibitor celecoxib attenuates joint contracture following immobilization in rat knees.
[So] Source:BMC Musculoskelet Disord;17(1):446, 2016 10 24.
[Is] ISSN:1471-2474
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this study is to clarify the following two points: First, whether a cyclooxygenase-2 mediated pathway is involved in the formation of immobilization-induced joint contracture and, second, the effectiveness of oral administration of non-steroidal anti-inflammatory drug celecoxib (CBX) for the prevention of myogenic and arthrogenic contracture following immobilization in a rat model. METHODS: Thirty male rats were randomly divided into three groups: immobilization (Im), Im + CBX, and control (n = 10 each). External fixation immobilized the right knee joint of Im and Im + CBX groups in flexion for 3 weeks. 50 mg/kg of CBX was administrated daily to the Im + CBX group during this period. The passive range of motion (ROM) of knee joints was measured before and after transection of knee flexor muscles and myogenic and arthrogenic ROM restrictions were calculated. The semitendinosus muscles and knee joints were investigated histologically to elucidate factors responsible for contracture. RESULTS: Myogenic ROM restrictions were exhibited both in Im and Im + CBX groups (44 ± 5 and 36 ± 8 °, respectively), but restrictions significantly decreased in the Im + CBX group compared to the Im group. Significant reductions of the muscle length ratios (Rt/Lt) and sarcomere number ratios (Rt/Lt) in knee flexor semitendinosus muscle, which are responsible for myogenic contracture, were also seen both in Im group (92 ± 5 and 92 ± 4 %, respectively) and Im + CBX group (97 ± 3 and 97 ± 3 %, respectively), but were inhibited by CBX administration (P < 0.05). Im and Im + CBX groups exhibited arthrogenic ROM restrictions with no significant differences (82 ± 3 and 83 ± 5 °, respectively). Posterior synovial length shortening and pathological changes (hemorrhage in joint cavities and capsule edema) in the knee joints were comparable between Im and Im + CBX groups. CONCLUSIONS: Oral administration of celecoxib partially reduced myogenic ROM restriction concomitantly with knee flexor muscle shortening following immobilization. These results imply that inflammation and nociception are involved in myogenic contracture formation independently of joint immobilization, and that CBX is effective in preventing joint contracture following immobilization in rats.
[Mh] Termos MeSH primário: Celecoxib/uso terapêutico
Contratura/prevenção & controle
Inibidores de Ciclo-Oxigenase 2/uso terapêutico
Ciclo-Oxigenase 2/metabolismo
Articulação do Joelho/efeitos dos fármacos
[Mh] Termos MeSH secundário: Administração Oral
Animais
Artrite
Celecoxib/administração & dosagem
Inibidores de Ciclo-Oxigenase 2/administração & dosagem
Modelos Animais de Doenças
Seres Humanos
Imobilização/efeitos adversos
Articulação do Joelho/patologia
Masculino
Músculo Esquelético/efeitos dos fármacos
Músculo Esquelético/patologia
Nociceptividade/efeitos dos fármacos
Amplitude de Movimento Articular/efeitos dos fármacos
Ratos
Ratos Wistar
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cyclooxygenase 2 Inhibitors); EC 1.14.99.1 (Cyclooxygenase 2); JCX84Q7J1L (Celecoxib)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171209
[Lr] Data última revisão:
171209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  5 / 1706 MEDLINE  
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[PMID]:28910410
[Au] Autor:Brown HE; Desai T; Murphy AJ; Pancholi H; Schmidt ZW; Swahn H; Liebl EC
[Ad] Endereço:Department of Biology, Denison University, Granville, Ohio, United States of America.
[Ti] Título:The function of Drosophila larval class IV dendritic arborization sensory neurons in the larval-pupal transition is separable from their function in mechanical nociception responses.
[So] Source:PLoS One;12(9):e0184950, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The sensory and physiological inputs which govern the larval-pupal transition in Drosophila, and the neuronal circuity that integrates them, are complex. Previous work from our laboratory identified a dosage-sensitive genetic interaction between the genes encoding the Rho-GEF Trio and the zinc-finger transcription factor Sequoia that interfered with the larval-pupal transition. Specifically, we reported heterozygous mutations in sequoia (seq) dominantly exacerbated the trio mutant phenotype, and this seq-enhanced trio mutant genotype blocked the transition of third instar larvae from foragers to wanderers, a requisite behavioral transition prior to pupation. In this work, we use the GAL4-UAS system to rescue this phenotype by tissue-specific trio expression. We find that expressing trio in the class IV dendritic arborization (da) sensory neurons rescues the larval-pupal transition, demonstrating the reliance of the larval-pupal transition on the integrity of these sensory neurons. As nociceptive responses also rely on the functionality of the class IV da neurons, we test mechanical nociceptive responses in our mutant and rescued larvae and find that mechanical nociception is separable from the ability to undergo the larval-pupal transition. This demonstrates for the first time that the roles of the class IV da neurons in governing two critical larval behaviors, the larval-pupal transition and mechanical nociception, are functionally separable from each other.
[Mh] Termos MeSH primário: Proteínas de Ligação a DNA/genética
Proteínas de Drosophila/genética
Drosophila melanogaster/fisiologia
Fatores de Troca do Nucleotídeo Guanina/genética
Proteínas do Tecido Nervoso/genética
Nociceptividade/fisiologia
Fosfoproteínas/genética
Proteínas Serina-Treonina Quinases/genética
Células Receptoras Sensoriais/fisiologia
[Mh] Termos MeSH secundário: Animais
Comportamento Animal
Proteínas de Ligação a DNA/metabolismo
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/genética
Feminino
Fatores de Troca do Nucleotídeo Guanina/metabolismo
Larva/fisiologia
Masculino
Mutação
Proteínas do Tecido Nervoso/metabolismo
Plasticidade Neuronal
Especificidade de Órgãos
Fenótipo
Fosfoproteínas/metabolismo
Proteínas Serina-Treonina Quinases/metabolismo
Pupa/fisiologia
Células Receptoras Sensoriais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (Drosophila Proteins); 0 (Guanine Nucleotide Exchange Factors); 0 (Nerve Tissue Proteins); 0 (Phosphoproteins); 0 (seq protein, Drosophila); 0 (trio protein, Drosophila); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184950


  6 / 1706 MEDLINE  
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[PMID]:28855331
[Au] Autor:Follansbee TL; Gjelsvik KJ; Brann CL; McParland AL; Longhurst CA; Galko MJ; Ganter GK
[Ad] Endereço:Department of Biology, College of Arts and Sciences, University of New England, Biddeford, Maine 04005.
[Ti] Título: Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.
[So] Source:J Neurosci;37(35):8524-8533, 2017 Aug 30.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a sensitized state. These findings are consistent with the observation that BMP receptor hyperactivation correlates with bone abnormalities and pain sensitization in fibrodysplasia ossificans progressiva (Kitterman et al., 2012). Because nociceptive sensitization is associated with chronic pain, these findings indicate that human BMP pathway components may represent targets for novel pain-relieving drugs.
[Mh] Termos MeSH primário: Proteínas Morfogenéticas Ósseas/metabolismo
Sensibilização do Sistema Nervoso Central/fisiologia
Proteínas de Drosophila/metabolismo
Drosophila/fisiologia
Nociceptividade/fisiologia
Nociceptores/fisiologia
Proteínas Smad/metabolismo
[Mh] Termos MeSH secundário: Animais
Limiar da Dor/fisiologia
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Proteins); 0 (Drosophila Proteins); 0 (Smad Proteins); 0 (dpp protein, Drosophila)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.3458-16.2017


  7 / 1706 MEDLINE  
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[PMID]:28818462
[Au] Autor:Wu YJ; Guernon J; McClure A; Luo G; Rajamani R; Ng A; Easton A; Newton A; Bourin C; Parker D; Mosure K; Barnaby O; Soars MG; Knox RJ; Matchett M; Pieschl R; Herrington J; Chen P; Sivarao DV; Bristow LJ; Meanwell NA; Bronson J; Olson R; Thompson LA; Dzierba C
[Ad] Endereço:Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492-7660, USA. Electronic address: yong-jin.wu@bms.com.
[Ti] Título:Discovery of non-zwitterionic aryl sulfonamides as Na 1.7 inhibitors with efficacy in preclinical behavioral models and translational measures of nociceptive neuron activation.
[So] Source:Bioorg Med Chem;25(20):5490-5505, 2017 Oct 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Since zwitterionic benzenesulfonamide Na 1.7 inhibitors suffer from poor membrane permeability, we sought to eliminate this characteristic by replacing the basic moiety with non-basic bicyclic acetals and monocyclic ethers. These efforts led to the discovery of the non-zwitterionic aryl sulfonamide 49 as a selective Na 1.7 inhibitor with improved membrane permeability. Despite its moderate cellular activity, 49 exhibited robust efficacy in mouse models of neuropathic and inflammatory pain and modulated translational electromyogram measures associated with activation of nociceptive neurons.
[Mh] Termos MeSH primário: Descoberta de Drogas
Modelos Biológicos
Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo
Neurônios/efeitos dos fármacos
Nociceptividade/efeitos dos fármacos
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Animais
Dor Crônica/induzido quimicamente
Dor Crônica/tratamento farmacológico
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Adjuvante de Freund
Células HEK293
Seres Humanos
Inflamação/induzido quimicamente
Inflamação/tratamento farmacológico
Masculino
Camundongos
Estrutura Molecular
Neurônios/metabolismo
Relação Estrutura-Atividade
Sulfonamidas/administração & dosagem
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NAV1.7 Voltage-Gated Sodium Channel); 0 (Sulfonamides); 9007-81-2 (Freund's Adjuvant)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE


  8 / 1706 MEDLINE  
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[PMID]:28777824
[Au] Autor:Filbrich L; Alamia A; Blandiaux S; Burns S; Legrain V
[Ad] Endereço:Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
[Ti] Título:Shaping visual space perception through bodily sensations: Testing the impact of nociceptive stimuli on visual perception in peripersonal space with temporal order judgments.
[So] Source:PLoS One;12(8):e0182634, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Coordinating spatial perception between body space and its external surrounding space is essential to adapt behaviors to objects, especially when they are noxious. Such coherent multisensory representation of the body extended into external space is conceptualized by the notion of peripersonal reference frame, mapping the portion of space in which somatic and extra-somatic inputs interact closely. Studies on crossmodal interactions between nociception and vision have been scarce. Here we investigated how the perception of visual stimuli, especially those surrounding the body, can be impacted by a nociceptive and potentially harmful stimulus inflicted on a particular body part. In two temporal order judgment tasks, participants judged which of two lateralized visual stimuli, presented either near or far from the body, had been presented first. Visual stimuli were preceded by nociceptive stimuli, either applied unilaterally (on one single hand) or bilaterally (on both hands simultaneously). In Experiment 1 participants' hands were always placed next to the visual stimuli presented near the trunk, while in Experiment 2 they could also be placed next to the visual stimuli presented far from the trunk. In Experiment 1, the presence of unilateral nociceptive stimuli prioritized the perception of visual stimuli presented in the same side of space as the stimulated hand, with a significantly larger effect when visual stimuli were presented near the body than when presented farther away. Experiment 2 showed that these visuospatial biases were related to the spatial congruency between the hand on which nociceptive stimuli were applied and the visual stimuli, independently of the relative distance of both the stimulated hand and the visual stimuli from the trunk. Indeed, nociceptive stimuli mostly impacted the perception of the closest visual stimuli. It is hypothesized that these crossmodal interactions may rely on representations of the space directly surrounding specific body parts.
[Mh] Termos MeSH primário: Julgamento/fisiologia
Nociceptividade/fisiologia
Percepção Espacial/fisiologia
Percepção Visual/fisiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Feminino
Seres Humanos
Masculino
Estimulação Luminosa
Tempo de Reação
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170805
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182634


  9 / 1706 MEDLINE  
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[PMID]:28674170
[Au] Autor:Moy JK; Khoutorsky A; Asiedu MN; Black BJ; Kuhn JL; Barragán-Iglesias P; Megat S; Burton MD; Burgos-Vega CC; Melemedjian OK; Boitano S; Vagner J; Gkogkas CG; Pancrazio JJ; Mogil JS; Dussor G; Sonenberg N; Price TJ
[Ad] Endereço:School of Behavioral and Brain Sciences, and.
[Ti] Título:The MNK-eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain.
[So] Source:J Neurosci;37(31):7481-7499, 2017 Aug 02.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Injury-induced sensitization of nociceptors contributes to pain states and the development of chronic pain. Inhibiting activity-dependent mRNA translation through mechanistic target of rapamycin and mitogen-activated protein kinase (MAPK) pathways blocks the development of nociceptor sensitization. These pathways convergently signal to the eukaryotic translation initiation factor (eIF) 4F complex to regulate the sensitization of nociceptors, but the details of this process are ill defined. Here we investigated the hypothesis that phosphorylation of the 5' cap-binding protein eIF4E by its specific kinase MAPK interacting kinases (MNKs) 1/2 is a key factor in nociceptor sensitization and the development of chronic pain. Phosphorylation of ser209 on eIF4E regulates the translation of a subset of mRNAs. We show that pronociceptive and inflammatory factors, such as nerve growth factor (NGF), interleukin-6 (IL-6), and carrageenan, produce decreased mechanical and thermal hypersensitivity, decreased affective pain behaviors, and strongly reduced hyperalgesic priming in mice lacking eIF4E phosphorylation ( ). Tests were done in both sexes, and no sex differences were found. Moreover, in patch-clamp electrophysiology and Ca imaging experiments on dorsal root ganglion neurons, NGF- and IL-6-induced increases in excitability were attenuated in neurons from mice. These effects were recapitulated in mice and with the MNK1/2 inhibitor cercosporamide. We also find that cold hypersensitivity induced by peripheral nerve injury is reduced in and mice and following cercosporamide treatment. Our findings demonstrate that the MNK1/2-eIF4E signaling axis is an important contributing factor to mechanisms of nociceptor plasticity and the development of chronic pain. Chronic pain is a debilitating disease affecting approximately one in three Americans. Chronic pain is thought to be driven by changes in the excitability of peripheral nociceptive neurons, but the precise mechanisms controlling these changes are not elucidated. Emerging evidence demonstrates that mRNA translation regulation pathways are key factors in changes in nociceptor excitability. Our work demonstrates that a single phosphorylation site on the 5' cap-binding protein eIF4E is a critical mechanism for changes in nociceptor excitability that drive the development of chronic pain. We reveal a new mechanistic target for the development of a chronic pain state and propose that targeting the upstream kinase, MAPK interacting kinase 1/2, could be used as a therapeutic approach for chronic pain.
[Mh] Termos MeSH primário: Adenosina Trifosfatases/metabolismo
Proteínas de Transporte de Cátions/metabolismo
Dor Crônica/fisiopatologia
Fator de Iniciação 4E em Eucariotos/metabolismo
Gânglios Espinais/fisiopatologia
Hiperalgesia/fisiopatologia
Plasticidade Neuronal
Nociceptividade
[Mh] Termos MeSH secundário: Animais
Dor Crônica/etiologia
ATPases Transportadoras de Cobre
Progressão da Doença
Feminino
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Dor Nociceptiva/etiologia
Dor Nociceptiva/fisiopatologia
Células Receptoras Sensoriais/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cation Transport Proteins); 0 (Eukaryotic Initiation Factor-4E); 0 (eIF4E protein, mouse); EC 3.6.1.- (Adenosine Triphosphatases); EC 3.6.3.4 (Atp7a protein, mouse); EC 3.6.3.54 (Copper-transporting ATPases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.0220-17.2017


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[PMID]:28640016
[Au] Autor:Sugiyama D; Kang S; Arpey N; Arunakul P; Usachev YM; Brennan TJ
[Ad] Endereço:From the Departments of Anesthesia (D.S., S.K., N.A., P.A., T.J.B.) and Pharmacology (Y.M.U., T.J.B.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa.
[Ti] Título:Hydrogen Peroxide Induces Muscle Nociception via Transient Receptor Potential Ankyrin 1 Receptors.
[So] Source:Anesthesiology;127(4):695-708, 2017 Oct.
[Is] ISSN:1528-1175
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: H2O2 has a variety of actions in skin wounds but has been rarely studied in deep muscle tissue. Based on response to the transient receptor potential ankyrin 1 antagonists after plantar incision, we hypothesized that H2O2 exerts nociceptive effects via the transient receptor potential ankyrin 1 in muscle. METHODS: Nociceptive behaviors in rats (n = 269) and mice (n = 16) were evaluated after various concentrations and volumes of H2O2 were injected into the gastrocnemius muscle or subcutaneous tissue. The effects of H2O2 on in vivo spinal dorsal horn neuronal activity and lumbar dorsal root ganglia neurons in vitro were evaluated from 26 rats and 6 mice. RESULTS: Intramuscular (mean ± SD: 1,436 ± 513 s) but not subcutaneous (40 ± 58 s) injection of H2O2 (100 mM, 0.6 ml) increased nociceptive time. Conditioned place aversion was evident after intramuscular (-143 ± 81 s) but not subcutaneous (-2 ± 111 s) injection of H2O2. These H2O2-induced behaviors were blocked by transient receptor potential ankyrin 1 antagonists. Intramuscular injection of H2O2 caused sustained in vivo activity of dorsal horn neurons, and H2O2 activated a subset of dorsal root ganglia neurons in vitro. Capsaicin nerve block decreased guarding after plantar incision and reduced nociceptive time after intramuscular H2O2. Nociceptive time after intramuscular H2O2 in transient receptor potential ankyrin 1 knockout mice was shorter (173 ± 156 s) compared with wild-type mice (931 ± 629 s). CONCLUSIONS: The greater response of muscle tissue to H2O2 may help explain why incision that includes deep muscle but not skin incision alone produces spontaneous activity in nociceptive pathways.
[Mh] Termos MeSH primário: Peróxido de Hidrogênio/farmacologia
Músculo Esquelético/efeitos dos fármacos
Nociceptividade/efeitos dos fármacos
Canais de Cátion TRPC/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anti-Infecciosos Locais/farmacologia
Modelos Animais de Doenças
Feminino
Gânglios Espinais/efeitos dos fármacos
Masculino
Nociceptores/efeitos dos fármacos
Células do Corno Posterior/efeitos dos fármacos
Ratos
Ratos Sprague-Dawley
Canal de Cátion TRPA1
Canais de Cátion TRPC/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents, Local); 0 (TRPA1 Cation Channel); 0 (TRPC Cation Channels); 0 (Trpa1 protein, rat); BBX060AN9V (Hydrogen Peroxide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1097/ALN.0000000000001756



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