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  1 / 2883 MEDLINE  
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[PMID]:28708877
[Au] Autor:Balázsfi DG; Zelena D; Farkas L; Demeter K; Barna I; Cserép C; Takács VT; Nyíri G; Gölöncsér F; Sperlágh B; Freund TF; Haller J
[Ad] Endereço:Department of Behavioral Neurobiology, Institute of Experimental Medicine, Budapest, Hungary.
[Ti] Título:Median raphe region stimulation alone generates remote, but not recent fear memory traces.
[So] Source:PLoS One;12(7):e0181264, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The median raphe region (MRR) is believed to control the fear circuitry indirectly, by influencing the encoding and retrieval of fear memories by amygdala, hippocampus and prefrontal cortex. Here we show that in addition to this established role, MRR stimulation may alone elicit the emergence of remote but not recent fear memories. We substituted electric shocks with optic stimulation of MRR in C57BL/6N male mice in an optogenetic conditioning paradigm and found that stimulations produced agitation, but not fear, during the conditioning trial. Contextual fear, reflected by freezing was not present the next day, but appeared after a 7 days incubation. The optogenetic silencing of MRR during electric shocks ameliorated conditioned fear also seven, but not one day after conditioning. The optogenetic stimulation patterns (50Hz theta burst and 20Hz) used in our tests elicited serotonin release in vitro and lead to activation primarily in the periaqueductal gray examined by c-Fos immunohistochemistry. Earlier studies demonstrated that fear can be induced acutely by stimulation of several subcortical centers, which, however, do not generate persistent fear memories. Here we show that the MRR also elicits fear, but this develops slowly over time, likely by plastic changes induced by the area and its connections. These findings assign a specific role to the MRR in fear learning. Particularly, we suggest that this area is responsible for the durable sensitization of fear circuits towards aversive contexts, and by this, it contributes to the persistence of fear memories. This suggests the existence a bottom-up control of fear circuits by the MRR, which complements the top-down control exerted by the medial prefrontal cortex.
[Mh] Termos MeSH primário: Encéfalo/fisiologia
[Mh] Termos MeSH secundário: Animais
Comportamento Animal
Eletrochoque
Medo/fisiologia
Halorrodopsinas/metabolismo
Imuno-Histoquímica
Masculino
Memória/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Substância Cinzenta Periaquedutal/metabolismo
Proteínas Proto-Oncogênicas c-fos/metabolismo
Serotonina/metabolismo
Gravação em Vídeo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Halorhodopsins); 0 (Proto-Oncogene Proteins c-fos); 333DO1RDJY (Serotonin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181264


  2 / 2883 MEDLINE  
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[PMID]:28489932
[Au] Autor:Li Z; Yin P; Chen J; Jin S; Liu J; Luo F
[Ad] Endereço:Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
[Ti] Título:CaMKIIα may modulate fentanyl-induced hyperalgesia via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway in rats.
[So] Source:PLoS One;12(5):e0177412, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Each of the lateral capsular division of central nucleus of amygdala(CeLC), periaqueductal gray (PAG), rostral ventromedial medulla(RVM) and spinal cord has been proved to contribute to the development of opioid-induced hyperalgesia(OIH). Especially, Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) in CeLC and spinal cord seems to play a key role in OIH modulation. However, the pain pathway through which CaMKIIα modulates OIH is not clear. The pathway from CeLC to spinal cord for this modulation was explored in the present study. Mechanical and thermal hyperalgesia were tested by von Frey test or Hargreaves test, respectively. CaMKIIα activity (phospho-CaMKIIα, p-CaMKIIα) was evaluated by western blot analysis. CaMKIIα antagonist (KN93) was micro-infused into CeLC, spinal cord or PAG, respectively, to evaluate its effect on behavioral hyperalgesia and p-CaMKIIα expression in CeLC, PAG, RVM and spinal cord. Then the underlying synaptic mechanism was explored by recording miniature excitatory postsynaptic currents (mEPSCs) on PAG slices using whole-cell voltage-clamp methods. Results showed that inhibition of CeLC, PAG or spinal CaMKIIα activity respectively by KN93, reversed both mechanical and thermal hyperalgesia. Microinjection of KN93 into CeLC decreased p-CaMKIIα expression in CeLC, PAG, RVM and spinal cord; while intrathecal KN93 can only block spinal but not CeLC CaMKIIα activity. KN93 injected into PAG just decreased p-CaMKIIα expression in PAG, RVM and spinal cord, but not in the CeLC. Similarly, whole-cell voltage-clamp recording found the frequency and amplitude of mEPSCs in PAG cells were decreased by KN93 added in PAG slice or micro-infused into CeLC in vivo. These results together with previous findings suggest that CaMKIIα may modulate OIH via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway.
[Mh] Termos MeSH primário: Analgésicos Opioides/efeitos adversos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo
Ativação Enzimática/efeitos dos fármacos
Fentanila/efeitos adversos
Hiperalgesia/induzido quimicamente
Medula Espinal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Núcleo Central da Amígdala/efeitos dos fármacos
Núcleo Central da Amígdala/metabolismo
Hiperalgesia/metabolismo
Masculino
Medição da Dor
Substância Cinzenta Periaquedutal/efeitos dos fármacos
Substância Cinzenta Periaquedutal/metabolismo
Ratos
Ratos Sprague-Dawley
Medula Espinal/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2); UF599785JZ (Fentanyl)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177412


  3 / 2883 MEDLINE  
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[PMID]:28434586
[Au] Autor:Motta SC; Carobrez AP; Canteras NS
[Ad] Endereço:Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil, Brazil.
[Ti] Título:The periaqueductal gray and primal emotional processing critical to influence complex defensive responses, fear learning and reward seeking.
[So] Source:Neurosci Biobehav Rev;76(Pt A):39-47, 2017 May.
[Is] ISSN:1873-7528
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The periaqueductal gray (PAG) has been commonly recognized as a downstream site in neural networks for the expression of a variety of behaviors and is thought to provide stereotyped responses. However, a growing body of evidence suggests that the PAG may exert more complex modulation of a number of behavioral responses and work as a unique hub supplying primal emotional tone to influence prosencephalic sites mediating complex aversive and appetitive responses. Of particular relevance, we review how the PAG is involved in influencing complex forms of defensive responses, such as circa-strike and risk assessment responses in animals. In addition, we discuss putative dorsal PAG ascending paths that are likely to convey information related to threatening events to cortico-hippocampal-amygdalar circuits involved in the processing of fear learning. Finally, we discuss the evidence supporting the role of the PAG in reward seeking and note that the lateral PAG is part of the circuitry related to goal-oriented responses mediating the motivation to hunt and perhaps drug seeking behavior.
[Mh] Termos MeSH primário: Emoções
Recompensa
[Mh] Termos MeSH secundário: Animais
Substância Cinzenta Periaquedutal
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170425
[St] Status:MEDLINE


  4 / 2883 MEDLINE  
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[PMID]:28374016
[Au] Autor:Samineni VK; Grajales-Reyes JG; Copits BA; O'Brien DE; Trigg SL; Gomez AM; Bruchas MR; Gereau RW
[Ad] Endereço:Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110; Washington University School of Medicine, St. Louis, MO 63110.
[Ti] Título:Divergent Modulation of Nociception by Glutamatergic and GABAergic Neuronal Subpopulations in the Periaqueductal Gray.
[So] Source:eNeuro;4(2), 2017 Mar-Apr.
[Is] ISSN:2373-2822
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The ventrolateral periaqueductal gray (vlPAG) constitutes a major descending pain modulatory system and is a crucial site for opioid-induced analgesia. A number of previous studies have demonstrated that glutamate and GABA play critical opposing roles in nociceptive processing in the vlPAG. It has been suggested that glutamatergic neurotransmission exerts antinociceptive effects, whereas GABAergic neurotransmission exert pronociceptive effects on pain transmission, through descending pathways. The inability to exclusively manipulate subpopulations of neurons in the PAG has prevented direct testing of this hypothesis. Here, we demonstrate the different contributions of genetically defined glutamatergic and GABAergic vlPAG neurons in nociceptive processing by employing cell type-specific chemogenetic approaches in mice. Global chemogenetic manipulation of vlPAG neuronal activity suggests that vlPAG neural circuits exert tonic suppression of nociception, consistent with previous pharmacological and electrophysiological studies. However, selective modulation of GABAergic or glutamatergic neurons demonstrates an inverse regulation of nociceptive behaviors by these cell populations. Selective chemogenetic activation of glutamatergic neurons, or inhibition of GABAergic neurons, in vlPAG suppresses nociception. In contrast, inhibition of glutamatergic neurons, or activation of GABAergic neurons, in vlPAG facilitates nociception. Our findings provide direct experimental support for a model in which excitatory and inhibitory neurons in the PAG bidirectionally modulate nociception.
[Mh] Termos MeSH primário: Ácido Glutâmico/metabolismo
Neurônios/metabolismo
Nociceptividade/fisiologia
Percepção da Dor/fisiologia
Substância Cinzenta Periaquedutal/fisiologia
Ácido gama-Aminobutírico/metabolismo
[Mh] Termos MeSH secundário: Animais
Masculino
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Modelos Animais
Neurônios/citologia
Neurônios/efeitos dos fármacos
Neurotransmissores/farmacologia
Nociceptividade/efeitos dos fármacos
Percepção da Dor/efeitos dos fármacos
Limiar da Dor/efeitos dos fármacos
Limiar da Dor/fisiologia
Substância Cinzenta Periaquedutal/efeitos dos fármacos
Transmissão Sináptica/efeitos dos fármacos
Transmissão Sináptica/fisiologia
Técnicas de Cultura de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurotransmitter Agents); 3KX376GY7L (Glutamic Acid); 56-12-2 (gamma-Aminobutyric Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE


  5 / 2883 MEDLINE  
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[PMID]:28368370
[Au] Autor:Iida T; Yi H; Liu S; Ikegami D; Zheng W; Liu Q; Takahashi K; Kashiwagi Y; Goins WF; Glorioso JC; Hao S
[Ad] Endereço:Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL, USA.
[Ti] Título:MnSOD mediated by HSV vectors in the periaqueductal gray suppresses morphine withdrawal in rats.
[So] Source:Gene Ther;24(5):314-324, 2017 May.
[Is] ISSN:1476-5462
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Morphine appears to be the most active metabolite of heroin; therefore, the effects of morphine are important in understanding the ramifications of heroin abuse. Opioid physical dependence (withdrawal response) may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. However, the exact mechanisms of morphine withdrawal (MW) are not clear yet, and its treatment remains elusive. Periaqueductal gray (PAG) is one of the important sites in the pathogenesis of MW. Here, we used recombinant herpes simplex virus (HSV) vectors that encode the sod2 gene expressing manganese superoxide dismutase (MnSOD) to evaluate its therapeutic potential in MW. Microinjection of HSV vectors expressing MnSOD into the PAG reduced the MW syndrome. MnSOD vectors suppressed the upregulated mitochondrial superoxide, and endoplasmic reticulum stress markers (glucose-related protein 78 (GRP78) and activating transcription factor 6 alpha (ATF6α)) in the PAG induced by MW. Immunostaining showed that mitochondrial superoxide, GRP78 and ATF6α were colocalized with neuronal nuclei (a neuronal-specific marker), suggesting that they are located in the neurons in the PAG. These results suggest that overexpression of MnSOD by HSV vectors may relieve opioid dependence. This study may provide a novel therapeutic approach to morphine physical withdrawal response.
[Mh] Termos MeSH primário: Terapia Genética
Morfina/efeitos adversos
Substância Cinzenta Periaquedutal/metabolismo
Simplexvirus/genética
Síndrome de Abstinência a Substâncias/terapia
Superóxido Dismutase/genética
[Mh] Termos MeSH secundário: Fator 6 Ativador da Transcrição/genética
Fator 6 Ativador da Transcrição/metabolismo
Animais
Vetores Genéticos/genética
Proteínas de Choque Térmico/genética
Proteínas de Choque Térmico/metabolismo
Masculino
Ratos
Ratos Sprague-Dawley
Superóxido Dismutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Activating Transcription Factor 6); 0 (Atf6 protein, rat); 0 (Heat-Shock Proteins); 0 (Hspa5 protein, rat); 76I7G6D29C (Morphine); EC 1.15.1.1 (Superoxide Dismutase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1038/gt.2017.22


  6 / 2883 MEDLINE  
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[PMID]:28321594
[Au] Autor:Chen Z; Chen X; Liu M; Liu S; Ma L; Yu S
[Ad] Endereço:Department of Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
[Ti] Título:Disrupted functional connectivity of periaqueductal gray subregions in episodic migraine.
[So] Source:J Headache Pain;18(1):36, 2017 Dec.
[Is] ISSN:1129-2377
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the altered dysfunction of PAG subregions were not totally detected up to now. The aim of this study is to investigate the altered functional connectivity of PAG subregions in EM patients. METHODS: The brain structural images and resting state functional MR imaging (rs-fMRI) data were obtained from 18 normal controls (NC) and 18 EM patients on 3.0 T MR system. Seven subregions of PAG were classified as bilateral ventrolateral PAG (vlPAG), lateral PAG (lPAG), dorsolateral PAG (dlPAG) and dorsomedial PAG (dmPAG). The functional connectivity maps of each PAG subregion were calculated, and Two sample t-test was applied with age and sex as covariables. RESULTS: Bilateral vlPAG and left dlPAG presented decreased functional connectivity, and the other subregions (bilateral lPAGs, right dlPAG and dmPAG) showed no significant altered functional connectivity in EM compared with NC. The brain regions with decreased functional connectivity mainly located in bilateral prefrontal cortex(PFC), middle temporal gyrus, primary motor area (PMA) and supplementary motor area (SMA) and right ventrolateral PFC (vlPFC) in EM patients in this study. Disease duration was positively related to the functional connectivity of bilateral vlPAG on the bilateral thalamus and putamen, left pallidum and right medial orbitofrontal gyrus in EM patients. CONCLUSION: The present study suggested that the dysfunction of bilateral vlPAG and left dlPAG presented in EM, and functional evaluation of PAG subregions may be help for the diagnosis and understanding of EM pathogenesis.
[Mh] Termos MeSH primário: Imagem por Ressonância Magnética
Transtornos de Enxaqueca/fisiopatologia
Substância Cinzenta Periaquedutal/fisiopatologia
Transmissão Sináptica/fisiologia
[Mh] Termos MeSH secundário: Adulto
Encéfalo
Mapeamento Encefálico
Dominância Cerebral/fisiologia
Feminino
Seres Humanos
Imagem por Ressonância Magnética/métodos
Masculino
Meia-Idade
Córtex Pré-Frontal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1186/s10194-017-0747-9


  7 / 2883 MEDLINE  
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Tufik, Sérgio
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[PMID]:28223243
[Au] Autor:Müller CJ; Quintino-Dos-Santos JW; Schimitel FG; Tufik S; Beijamini V; Canteras NS; Schenberg LC
[Ad] Endereço:Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
[Ti] Título:On the verge of a respiratory-type panic attack: Selective activations of rostrolateral and caudoventrolateral periaqueductal gray matter following short-lasting escape to a low dose of potassium cyanide.
[So] Source:Neuroscience;348:228-240, 2017 Apr 21.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Intravenous injections of potassium cyanide (KCN) both elicit escape by its own and facilitate escape to electrical stimulation of the periaqueductal gray matter (PAG). Moreover, whereas the KCN-evoked escape is potentiated by CO , it is suppressed by both lesions of PAG and clinically effective treatments with panicolytics. These and other data suggest that the PAG harbors a hypoxia-sensitive alarm system the activation of which could both precipitate panic and render the subject hypersensitive to CO . Although prior c-Fos immunohistochemistry studies reported widespread activations of PAG following KCN injections, the employment of repeated injections of high doses of KCN (>60µg) in anesthetized rats compromised both the localization of KCN-responsive areas and their correlation with escape behavior. Accordingly, here we compared the brainstem activations of saline-injected controls (air/saline) with those produced by a single intravenous injection of 40-µg KCN (air/KCN), a 2-min exposure to 13% CO (CO /saline), or a combined stimulus (CO /KCN). Behavioral effects of KCN microinjections into the PAG were assessed as well. Data showed that whereas the KCN microinjections were ineffective, KCN intravenous injections elicited escape in all tested rats. Moreover, whereas the CO alone was ineffective, it potentiated the KCN-evoked escape. Compared to controls, the nucleus tractus solitarius was significantly activated in both CO /saline and CO /KCN groups. Additionally, whereas the laterodorsal tegmental nucleus was activated by all treatments, the rostrolateral and caudoventrolateral PAG were activated by air/KCN only. Data suggest that the latter structures are key components of a hypoxia-sensitive suffocation alarm which activation may trigger a panic attack.
[Mh] Termos MeSH primário: Comportamento Animal/efeitos dos fármacos
Reação de Fuga/efeitos dos fármacos
Neurônios/efeitos dos fármacos
Pânico/efeitos dos fármacos
Substância Cinzenta Periaquedutal/efeitos dos fármacos
Cianeto de Potássio/farmacologia
[Mh] Termos MeSH secundário: Animais
Masculino
Neurônios/metabolismo
Substância Cinzenta Periaquedutal/metabolismo
Proteínas Proto-Oncogênicas c-fos/metabolismo
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins c-fos); MQD255M2ZO (Potassium Cyanide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170223
[St] Status:MEDLINE


  8 / 2883 MEDLINE  
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[PMID]:28219988
[Au] Autor:Doyle HH; Eidson LN; Sinkiewicz DM; Murphy AZ
[Ad] Endereço:Neuroscience Institute, Georgia State University, Atlanta, Georgia 30303.
[Ti] Título:Sex Differences in Microglia Activity within the Periaqueductal Gray of the Rat: A Potential Mechanism Driving the Dimorphic Effects of Morphine.
[So] Source:J Neurosci;37(12):3202-3214, 2017 Mar 22.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although morphine remains the primary drug prescribed for alleviation of severe or persistent pain, both preclinical and clinical studies have shown that females require two to three times more morphine than males to produce comparable levels of analgesia. In addition to binding to the neuronal µ-opioid receptor, morphine binds to the innate immune receptor toll-like receptor 4 (TLR4) localized primarily on microglia. Morphine action at TLR4 initiates a neuroinflammatory response that directly opposes the analgesic effects of morphine. Here, we test the hypothesis that the attenuated response to morphine observed in females is the result of increased microglia activation in the periaqueductal gray (PAG), a central locus mediating the antinociceptive effects of morphine. We report that, whereas no overall sex differences in the density of microglia were noted within the PAG of male or female rats, microglia exhibited a more "activated" phenotype in females at baseline, with the degree of activation a significant predictor of morphine half-maximal antinociceptive dose (ED ) values. Priming microglia with LPS induced greater microglia activation in the PAG of females compared with males and was accompanied by increased transcription levels of IL-1ß and a significant rightward shift in the morphine dose-response curve. Blockade of morphine binding to PAG TLR4 with (+)-naloxone potentiated morphine antinociception significantly in females such that no sex differences in ED were observed. These results demonstrate that PAG microglia are sexually dimorphic in both basal and LPS-induced activation and contribute to the sexually dimorphic effects of morphine in the rat. We demonstrate that periaqueductal gray (PAG) microglia contribute to the sexually dimorphic effects of morphine. Specifically, we report that increased activation of microglia in the PAG contributes to the attenuated response to morphine observed in females. Our data further implicate the innate immune receptor toll-like receptor 4 (TLR4) as an underlying mechanism mediating these effects and establish that TLR4 inhibition in the PAG of females reverses the sex differences in morphine responsiveness. These data suggest novel methods to improve current opioid-based pain management via inhibition of glial TLR4 and illustrate the necessity for sex-specific research and individualized treatment strategies for the management of pain in men and women.
[Mh] Termos MeSH primário: Microglia/efeitos dos fármacos
Microglia/fisiologia
Morfina/administração & dosagem
Substância Cinzenta Periaquedutal/efeitos dos fármacos
Substância Cinzenta Periaquedutal/fisiologia
Receptor 4 Toll-Like/metabolismo
[Mh] Termos MeSH secundário: Animais
Contagem de Células
Relação Dose-Resposta a Droga
Resistência a Medicamentos/fisiologia
Feminino
Masculino
Microglia/citologia
Substância Cinzenta Periaquedutal/citologia
Ratos
Ratos Sprague-Dawley
Caracteres Sexuais
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tlr4 protein, rat); 0 (Toll-Like Receptor 4); 76I7G6D29C (Morphine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170923
[Lr] Data última revisão:
170923
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.2906-16.2017


  9 / 2883 MEDLINE  
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[PMID]:28206989
[Au] Autor:Yi H; Iida T; Liu S; Ikegami D; Liu Q; Iida A; Lubarsky DA; Hao S
[Ad] Endereço:Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
[Ti] Título:IL-4 mediated by HSV vector suppresses morphine withdrawal response and decreases TNFα, NR2B, and pC/EBPß in the periaqueductal gray in rats.
[So] Source:Gene Ther;24(4):224-233, 2017 Apr.
[Is] ISSN:1476-5462
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chronic opiates induce the development of physical dependence. Opioid physical dependence characterized by withdrawal symptoms, may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. Elucidation of the mechanisms involved in physical dependence is crucial to developing more effective treatment strategies for opioid dependence. Chronic morphine induces production of proinflammatory cytokines in regional-specific sites of the brain. Interleukin-4 (IL-4) is a prototypical anti-inflammatory cytokine that globally suppresses proinflammatory cytokines. Here, we used recombinant herpes simplex virus vector S4IL4 that encode mouse il4 gene to evaluate the therapeutic potential of IL-4 in naloxone-precipitation morphine withdrawal (MW). One week after microinjection of the vector S4IL4 into the PAG LacZ or mouse IL-4 immunoreactivity in the vlPAG was visualized. ELISA assay showed that vector S4IL4 into the PAG induced the expression of IL-4. S4IL4 blunted the morphine withdrawal syndrome. S4IL4 suppressed the upregulated TNFα, NR2B and pC/EBPß in the PAG induced by MW. These results show that inhibition of proinflammatory factor in the PAG suppressed MW. This study may provide a novel therapeutic approach to morphine physical withdrawal symptoms.
[Mh] Termos MeSH primário: Interleucina-4/uso terapêutico
Morfina/efeitos adversos
Síndrome de Abstinência a Substâncias/terapia
Transtornos Relacionados ao Uso de Substâncias/terapia
[Mh] Termos MeSH secundário: Animais
Citocinas/metabolismo
Vetores Genéticos/uso terapêutico
Seres Humanos
Interleucina-4/genética
Camundongos
Naloxona/administração & dosagem
Substância Cinzenta Periaquedutal/efeitos dos fármacos
Substância Cinzenta Periaquedutal/metabolismo
Ratos
Simplexvirus/genética
Síndrome de Abstinência a Substâncias/genética
Síndrome de Abstinência a Substâncias/patologia
Transtornos Relacionados ao Uso de Substâncias/genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Tumor Necrosis Factor-alpha); 207137-56-2 (Interleukin-4); 36B82AMQ7N (Naloxone); 76I7G6D29C (Morphine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170217
[St] Status:MEDLINE
[do] DOI:10.1038/gt.2017.11


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[PMID]:28155029
[Au] Autor:Chen Z; Chen X; Liu M; Liu S; Ma L; Yu S
[Ad] Endereço:Department of Radiology, Chinese PLA General Hospital, Beijing, 100853, China.
[Ti] Título:Texture features of periaqueductal gray in the patients with medication-overuse headache.
[So] Source:J Headache Pain;18(1):14, 2017 Dec.
[Is] ISSN:1129-2377
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Periaqueductal gray (PAG) is the descending pain modulatory center, and PAG dysfunction had been recognized in migraine. Here we propose to investigate altered PAG texture features (quantitative approach for extracting texture descriptors for images) in the patients with medication-overuse headache (MOH) based on high resolution brain structural image to understand the MOH pathogenesis. METHODS: The brain structural images were obtained from 32 normal controls (NC) and 44 MOH patients on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template, and the individual PAG segment was performed by applying the deformation field to the PAG template after structural image segment. Grey-level co-occurrence matrix (GLCM) was performed to measure the texture parameters including angular second moment (ASM), Contrast, Correlation, inverse difference moment (IDM) and Entropy. RESULTS: Contrast was increased in MOH patients (9.28 ± 3.11) compared with that in NC (7.94 ± 0.65) (P < 0.05), and other texture features showed no significant difference between MOH and NC (P > 0.05). The area under the ROC curve was 0.697 for Contrast in the distinction of MOH from NC, and the cut-off value of Contrast was 8.11 with sensitivity 70.5% and specificity 62.5%. The contrast was negatively with the sleep scores (r = -0.434, P = 0.003). CONCLUSION: Texture Contrast could be used to identify the altered MR imaging characteristics in MOH in understanding the MOH pathogenesis, and it could also be considered as imaging biomarker in for MOH diagnosis.
[Mh] Termos MeSH primário: Transtornos da Cefaleia Secundários/diagnóstico por imagem
Imagem por Ressonância Magnética/métodos
Substância Cinzenta Periaquedutal/diagnóstico por imagem
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170204
[St] Status:MEDLINE
[do] DOI:10.1186/s10194-017-0727-0



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