RESUMO
The colloidal borescope, using colloidal particle motion, is used to monitor the flow velocities and directions of groundwater. It integrates advanced techniques such as microscopy, high-speed photography, and big data computing and enjoys high sensitivity at the micron level. However, In the same well, the groundwater flow velocity monitored by colloidal hole mirror is varies greatly from that obtained by conventional hydrogeological monitoring, such as pumping test. In order to solve this problem, the stability catcher and stratified packer are designed to control the interference of the vertical flow in drilling, and to monitor the flow velocity and direction of groundwater velocity at the target aquifer and target fracture. Five wells with different aquifers and different groundwater types were selected for monitoring in south-central China. The instantaneous velocity and direction are converted into east-west component and north-south component, the average velocity and direction is calculated according to the time of 10 min, and the particle trajectory diagram is established. Based on these results, it proposed a concept of cumulative flow velocity. Using curve-fitting equations, the limits of cumulative flow velocities as the monitoring time tends to infinity were then calculated as the actual flow velocities of the groundwater. The permeability coefficient of aquifer is calculated by using the fissure ratio of aquifer, hydraulic slope and flow velocity, and compared with the permeability coefficient obtained by pumping test. The results are as follows: (1) The variation coefficient of the instantaneous flow velocity measured at the same depth in the same well at different times is greater than that of the time average flow velocity and greater than that of the cumulative flow velocity. The variation coefficient of the actual velocity is the smallest, indicating that the risk of using the actual flow velocity is lower. (2) The variation coefficient of the flow rate monitored at different depths in the same well is mainly controlled by the properties of the aquifer. The more uniform water storage space in the aquifer, the smaller the variation coefficient. (3) The comparison between the permeability coefficient obtained by monitoring and the permeability coefficient obtained by pumping test shows that the flow of structural fissure water controlled by planar fissure is more surface flow, and the results are consistent. When the groundwater flow is controlled by pores and solution gaps, the flow channel is complicated, which is easy to produce turbulent flow, and the result consistency is poor. (4) According to different research accuracy requirements, different monitoring and calculation methods can be selected for different aquifers and groundwater types. Researches show that, the permeability coefficient calculated for the actual flow velocity in well DR01 is the same as that calculated for the pumping test. The aquifer characteristics reflected by the coefficient of variation of the actual flow velocity in the same aquifer are more realistic. The pumping test method obtains the comprehensive parameters of a certain aquifer, and this method can be used to monitor a certain fissure. In this paper, the new technology developed for monitoring, and the new algorithm established for data processing, can accurately obtain the flow velocity and direction of groundwater, using capsule hole mirror monitoring method. The key parameters of hydrogeology can be obtained by using one well, which can reduce the time and cost input and improve the work efficiency.
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p300 and its homolog cyclic AMP response element binding protein (CBP) are coactivators that were identified to participate in many biological processes including neural development and cognition. Their roles within the rodent spinal cord have not been reported systematically; in this study, their spatiotemporal distribution in the spinal cord of adult rat following chronic constriction injury (CCI) was studied. p300 and CBP expressed predominantly in nuclei in the gray matter of rat spinal cord. Rats undergoing CCI surgery showed increased p300/CBP immunoreactivity (IR) compared with normal control and sham-operated rats. The number of IR cells reached the peak at day 14 following CCI compared with those on day 3, 7, and 21, accompanied with significant behavioral changes of neuropathic pain. Cell-type determination by immunofluorescence at day 14 following CCI revealed that p300 and CBP expressed in neurons, but not in astrocytes or microglial cells. These results suggest that p300 and CBP are probably involved in the maintenance of neuropathic pain on spinal cord level. Furthermore, p300 and CBP may serve as a sensor only in neurons but not in astrocytes or microglia cells in the adult rat spinal cord.
Assuntos
Envelhecimento/metabolismo , Proteína p300 Associada a E1A/metabolismo , Proteínas de Membrana/metabolismo , Fosfoproteínas/metabolismo , Células do Corno Posterior/metabolismo , Células do Corno Posterior/patologia , Animais , Comportamento Animal , Constrição , Imuno-Histoquímica , Masculino , Neuralgia/metabolismo , Neuralgia/patologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação , Fatores de TempoRESUMO
OBJECTIVE: In laryngeal microsurgery, the insertion of the suspension laryngoscope is a strong stimulus that may cause hemodynamic fluctuations and adverse cardiovascular events. The purpose of this study was to compare the effect of preemptive treatment with esketamine and sufentanil on maintaining hemodynamics and reducing the occurrence of adverse cardiovascular events during the insertion of suspension laryngoscope. METHODS: In this double-blind randomized controlled trial, patients undergoing general anesthesia for laryngeal microsurgery were randomly assigned (1:1) to esketamine 0.5 mg kg-1 (esketamine group) and sufentanyl 0.125 µg kg-1 (sufentanil group) before inserting the laryngoscope, respectively. RESULTS: During the insertion of suspension laryngoscope, the incidence of bradycardia (HR < 60 beats/min) was 39.3% (22/56) in esketamine group, lower than 60.0% (33/55) in sufentanil group (odds ratio [OR], 2.32 [95% CI, 1.11-5.08]; p = 0.029). The incidence of hypotension (MAP <65 mmHg) was 33.9% (19/56) in esketamine group, lower than 56.4% (31/55) in sufentanil group (odds ratio [OR], 2.52 [95% CI, 1.91-5.27]; p = 0.018). The frequency of hypotension in esketamine group was lower than that in sufentanil group (0.36 ± 0.52 vs. 0.56 ± 0.50, p = 0.035). The time-weighted average of HR dropping above 30% of baseline was smaller in esketamine group than in sufentanil group (0.52 ± 2.06 vs. 1.08 ± 2.77, p = 0.006). CONCLUSIONS: These findings showed that compared with preemptive treatment of sufentanil (0.125 µg kg-1 ), esketamine (0.5 mg kg-1 ) was effective in reducing the incidence of cardiovascular adverse events, including bradycardia and hypotension induced by the insertion of suspension laryngoscope during the laryngeal microsurgery. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3021-3027, 2023.
Assuntos
Hipotensão , Laringoscópios , Humanos , Sufentanil/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Método Duplo-CegoRESUMO
BACKGROUND: Neuropathic pain is detrimental to human health; however, its pathogenesis still remains largely unknown. Overexpression of pain-associated genes and increased nociceptive somato-sensitivity are well observed in neuropathic pain. The importance of epigenetic mechanisms in regulating the expression of pro- or anti-nociceptive genes has been revealed by studies recently, and we hypothesize that the transcriptional coactivator and the histone acetyltransferase E1A binding protein p300 (p300), as a part of the epigenetic mechanisms of gene regulation, may be involved in the pathogenesis of neuropathic pain induced by chronic constriction injury (CCI). To test this hypothesis, two different approaches were used in this study: (I) down-regulating p300 with specific small hairpin RNA (shRNA) and (II) chemical inhibition of p300 acetyltransferase activity by a small molecule inhibitor, C646. RESULTS: Using the CCI rat model, we found that the p300 expression was increased in the lumbar spinal cord on day 14 after CCI. The treatment with intrathecal p300 shRNA reversed CCI-induced mechanical allodynia and thermal hyperalgesia, and suppressed the expression of cyclooxygenase-2 (COX-2), a neuropathic pain-associated factor. Furthermore, C646, an inhibitor of p300 acetyltransferase, also attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord. CONCLUSIONS: The results suggest that, through its acetyltransferase activity in the spinal cord after CCI, p300 epigenetically plays an important role in neuropathic pain. Inhibiting p300, using interfering RNA or C646, may be a promising approach to the development of new neuropathic pain therapies.
Assuntos
Acetiltransferases/metabolismo , Dor Crônica/metabolismo , Epigenômica , Neuralgia/enzimologia , Neuralgia/genética , Acetiltransferases/genética , Animais , Dor Crônica/genética , Constrição Patológica , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição de p300-CBPRESUMO
OBJECTIVE: To assess the association between membrane type 1 matrix metalloproteinase gene (MT1-MMP, MMP14) polymorphisms and osteoporosis in Zhuang men from Baise region of Guangxi. METHODS: Genotypes of 5 loci (rs1003349, rs3751488, rs2269213, rs2236303 and rs743257) of MMP14 gene in 301 Zhuang men were determined with single base extension methods, and bone mineral density (BMD) at left calcaneus was evaluated with quantitative ultrasound with measured values of broadband ultrasonic attenuation (BUA). The subjects were divided according to BMD into osteoporosis group, osteopenia group and normal bone density group. RESULTS: All selected loci were in Hardy-Weinberg equilibrium (P> 0.05). By multiple linear stepwise regression analysis, polymorphisms of the five loci were not associated with BUA. But a significant higher risk of osteoporosis was found in individuals with MMP14 rs1003349 GT genotype (vs. GG genotype; P<0.05) and rs2236303 CC and CT genotypes (vs. TT genotype; P<0.05). Genetic linkage between rs1003349 and rs2236303 was also discovered (D'= 0.839, r(2) = 0.458, P<0.01). Compared with the normal bone density group, the frequency of a G-T haplotype of rs1003349 and rs2236303 was significantly lower in the osteoporosis group (P<0.05). And the risk of osteoporosis for individuals with G-C and T-C haplotypes was 2.556 (95% CI: 1.029-6.349, P = 0.038) and 5.111 (95% CI: 1.341-19.485, P = 0.011) compared with G-T haplotype. CONCLUSION: Polymorphisms of rs1003349 and rs2236303 loci of MMP14 gene are associated with the susceptibility of osteoporosis in Zhuang men in Guangxi. G-C and T-C haplotypes for loci rs1003349 and rs2236303 may increase the disease risk.
Assuntos
Metaloproteinase 14 da Matriz/genética , Osteoporose/genética , Adulto , Idoso , Densidade Óssea/genética , China , Ligação Genética , Predisposição Genética para Doença , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/enzimologia , Polimorfismo GenéticoRESUMO
Comprehending the distribution pattern and enrichment rule of the heavy metal cadmium (Cd) in soil and grasping its activity and influencing factors is crucial for guaranteeing the soil environment safety of agricultural and construction land and improving the overall quality of the soil environment. The concentration of heavy metal Cd in the quaternary profile of Nansha was measured, and the pollution level was evaluated using the geographical accumulation index (Igeo) and potential ecological risk index (Er). Then, we determined the correlation between the total amount of Cd and the physicochemical properties of the soil using factor analysis (FA-MLR). The results showed that the average content of Cd in shallow soil (0-20 cm) in the Nansha area was 0.54 mg·kg-1, and the soil was mainly weakly acidic and neutral. The average content of Cd in deep soil (150-200 cm) was 0.42 mg·kg-1, and the soil was mainly neutral. At the same time, the variation coefficient of Cd content in shallow soil was significantly greater than that in deep soil, and Cd content tended to be consistent with the increase in depth. The Cd content of quaternary sediments showed a bimodal distribution with depth, reaching a peak at 20-25 m and 5-10 m, respectively, whereas the core sediments in this section were mostly marine sediments of silt and silty clay, with high cation exchange capacity and organic matter. The Igeo and Er of Cd in the fine-grained sediments dominated by clayey soil were significantly higher than those in the coarse-grained sediments dominated by sandy soil. The difference in soil pH value led to the different trend of Cd content with depth; the migration amount and vertical migration depth of Cd in deep soil were greater in the acidic environment. The influence of pH change on the migration and transformation of Cd was not completely reflected in the influence on the total amount of Cd, but more importantly, it changed the effective state of Cd, thus affecting the bioavailability of Cd. The unstable Cd composed of water-soluble, ion-exchangeable, and carbonate states accounted for 37.92%-49.10% of the total Cd, resulting in a strong instability of soil Cd. Further investigation on the migration and toxicity of heavy metals associated with human health risks is needed in future studies.
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Metais Pesados , Poluentes do Solo , Disponibilidade Biológica , Cádmio/análise , China , Monitoramento Ambiental/métodos , Humanos , Metais Pesados/análise , Solo/química , Poluentes do Solo/análiseRESUMO
Groundwater resources in the Leizhou Peninsula provide a strong support for the economic and social development. Therefore, understanding the chemical characteristics and formation mechanism of groundwater in this area is necessary for the rational exploitation and sustainable utilization of water resources. In this study, 43 groundwater samples were collected, and the hydrochemical characteristics and controlling factors were analyzed by descriptive statistical analysis, Piper triangular diagrams, ArcGIS spatial interpolation, Gibbs diagram, and ion ratios. The results showed that:â The anions and cations of the groundwater in the study area were mainly HCO3-, Ca2+, and Na+, and the hydrochemical types were mainly HCO3-Cl-Na-Ca, HCO3-Cl-Na-Ca-Mg, HCO3-Cl-Na-Mg, and HCO3-Na. The contents of Cl-, SO42-, and Na+were higher in the west of Leizhou City compared to other areas. The sites with higher contents of HCO3-, NO3-, Ca2+, Mg2+, and K+ were mainly concentrated in the southwest and eastern coastal areas. â¡ The chemical evolution of groundwater was mainly affected by water-rock interaction, cation alternating adsorption, and anthropogenic activities. The sources of Na+ and K+ were mainly from evaporative and silicate rocks, Ca2+ and Mg2+ were mainly from carbonate karstification, while NO3- originated from anthropogenic activities.
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Água Subterrânea , Poluentes Químicos da Água , Cidades , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Qualidade da ÁguaRESUMO
Cadmium (Cd) pollution poses a threat to human health, and research on Cd bioavailability as well as its ecological risk assessment can help prevent and mitigate Cd hazards. The enrichment characteristics and variability of Cd were investigated in sea-land interaction soil fractions and the associated environmental and ecological risks were evaluated using the accumulation index (Igeo), potential ecological hazard index (Er), and risk assessment coding (RAC). The results showed that:â The Cd content of miscellaneous fill material was typically lower than 0.3 mg·kg-1 and that of plain full was higher than 0.3 mg·kg-1. The Cd content of marine sediment was significantly higher than that of continental sediments, averaging 0.36 and 0.10 mg·kg-1, respectively. The concentration of Cd in marine sediments buried at shallow depths (<5 m) was generally higher than at greater depths (>5 m). â¡ There was a moderate correlation between Cd and CEC in artificial fill (Q4ml; correlation coefficient=0.52, P<0.05). There was a weak correlation between Cd and organic matter in the marine sediments (correlation coefficient=0.49, P<0.05). Total cadmium and the physical and chemical properties of soil had a significant influence on the fraction of soil cadmium. ⢠The Igeo of artificially fill and marine sediment was dominated by the relationship 1 < Igeo < 2, which indicated a moderate level of pollution. The Er of artificial fill and marine sediment was mainly 80 < Er < 160, indicating a high potential ecological hazard. Soil acid-extractable Cd accounted for more than 50% of the total Cd in each drill hole, which generally indicated a very high potential ecological risk. These results provide a basis for environmental and agricultural decision-making and provide theoretical guidance for soil pollution investigations and remediation.
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Metais Pesados , Poluentes Químicos da Água , Disponibilidade Biológica , Cádmio/análise , China , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Metais Pesados/análise , Medição de Risco , Rios , Solo , Poluentes Químicos da Água/análiseRESUMO
Source identification and health risk assessment of heavy metals in groundwater is one of the key issues in China's new era of environmental management. In order to reveal the status, sources, and health risk of pollutants in groundwater of the Leizhou Peninsula, 44 groundwater samples were collected, and the concentrations and spatial distribution of Cr, Mn, Cu, Zn, As, Cd, Hg, and Pb were measured and analyzed. The sources of heavy metals in groundwater were then determined through correlation coefficient and principal component analysis. Finally, the health risk model was used to evaluate the different health risks associated with these heavy metals. The results showed that the average value of heavy metal elements in groundwater of the Leizhou Peninsula does not inferior to the class â ¡ water quality standard(GB/T 14848-2017). However, As, Mn, and Cd do not meet the standard. The overall spatial distribution indicated obvious spatial differences, with higher values in the south than in the north. Heavy metal sources can be identified as three principal components (PCs). PC1 (Cu, Zn, Cd, and Pb) metals mainly originate from industrial, agricultural, and traffic sources. PC2 (Cr, Mn, and As) sources can be both natural and man-made, and PC3 (Hg) sources are primarily man-made. For the groundwater of the Leizhou Peninsula, the health risks of 8 metals are with the acceptable range, the carcinogenic risk of adults is higher than that of children, and the risk of drinking exposure is higher than that of skin exposure. The study shows that the environmental protection department should encourage the rational exploitation of groundwater resources and control the sources of pollution to reduce health risks.
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Poluentes Ambientais , Água Subterrânea , Metais Pesados , Adulto , Criança , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de RiscoRESUMO
Cadmium pollution poses a threat to human health. The examination of spatial distribution of Cd in soils can be used to assess the risks posed to humans and the environment. The enrichment characteristics and variation rules of heavy metal cadmium in the soil were revealed by analyzing the concentration and fractions of Cd in the soil at different depths in the sea-land interaction zone. The results showed that: â the concentration of Cd in the surface water of Nansha was lower than 0.0001 mg ·L-1, and the physical and chemical properties of river sediments showed spatial differences with the boundary of "Shang Heng-li River". Cd was mainly deposited in the north of the "Shang Heng-li River", with the mean total Cd of 2.71 mg ·kg-1. The total Cd in the sediment of the "Shang Heng-li River" and the rivers south of it were 0.062-0.39 mg ·kg-1, which caused minimal harm to the marine environment. â¡ The content of Cd in the soil profile gradually decreased with an increase in soil burial depth. The median content of Cd in the five layers, including 0-20 cm, 20-50 cm, 50-90 cm, 90-140 cm, and 140-200 cm, were 0.51, 0.50, 0.45, 0.42, and 0.33 mg ·kg-1, respectively, and the dispersion degree gradually decreased with an increase in buried depth; the vertical migration amount and migration depth of Cd increased significantly in soils with pH less than 5. ⢠The residual Cd in the soil accounted for approximately 40%, and the trend was typically flat with a change in buried depth. The median proportion of acid soluble Cd was consistent with the change in pH and increased with an increase in the buried depth of the profile, while the median proportion of reducible Cd was consistent with the change in iron and manganese content, and decreased with an increase in buried depth of section. These results have important guiding significance for the regional prevention and control of Cd pollution in farmland surrounding cities and the treatment and remediation of polluted soil.
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Metais Pesados , Poluentes do Solo , Cádmio/análise , China , Cidades , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Metais Pesados/análise , Rios , Solo , Poluentes do Solo/análiseRESUMO
OBJECTIVE: To observe the effect of intrathecal injection of ketamine and clonidine for chronic constriction injury (CCI) in rats. METHODS: Thirty-two SD male rats weighing 220-280 g were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. A catheter was implanted in the subarachnoid space at the lumbal region and CCI rat models were made successfully. On the 4th day after the surgery, the rats were randomly divided into 4 group: a control group,injecting 0.9%NS 20 microL intrathecally; a ketamine group, injecting ketamine 1 mg/kg(20 microL) intrathecally; a clonidine group (CL), injecting clonidine 20 microg/kg (20 microL) intrathecally; a combined ketamine and clonidine group, injecting ketamine 0.5mg/kg and clonidine 10 g/kg (20 microL) intrathecally, once a day for 1 week. BME-410A Plantar Analgesia Tester was used to measured pain threshold before the administration and 30 min after the administration. The rats were killed after the test was finished. And then we detected the nitric oxide synthase (NOS) activity and the NO production in the spinal cord. RESULTS: The combined injection of ketamine (0.5mg/kg)and clonidine(10 g/kg) produced significantly more potent analgesia than the injection of ketamine (1 mg/ kg) or clonidine (20 microg/ kg)alone. The NOS activity and the production of NO in the combined injection group were significantly lower than those of the single injection group (P<0.05). The weight of rats post-administration increased obviously in the 4 groups (P<0.05). CONCLUSION: The combined injection of ketamine and clonidine can produce synergistic ab-irritation without obvious side effects.
Assuntos
Analgésicos , Clonidina , Ketamina , Neuralgia/tratamento farmacológico , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Animais , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Clonidina/uso terapêutico , Combinação de Medicamentos , Injeções Espinhais , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/uso terapêutico , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
BACKGROUND: Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood. METHODS: We used the rat chronic constriction injury (CCI) model for research, and degraded SNAP-25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP-25, GLT, and GAT-1 were assayed using RT-PCR and Western blotting. RESULTS: SNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP- 25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P < 0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P < 0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment. CONCLUSIONS: SNAP-25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT-1.
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Sistema X-AG de Transporte de Aminoácidos/metabolismo , Neuralgia/metabolismo , Neuroglia/metabolismo , Proteína 25 Associada a Sinaptossoma/metabolismo , Sistema X-AG de Transporte de Aminoácidos/genética , Animais , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de GABA , Masculino , Neuralgia/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia , Proteína 25 Associada a Sinaptossoma/genéticaAssuntos
Analgésicos Opioides/administração & dosagem , Pupila/efeitos dos fármacos , Sufentanil/administração & dosagem , Adulto , Idoso , Analgésicos Opioides/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Sufentanil/farmacologiaRESUMO
The pathogenesis of neuropathic pain remains largely unknown. Epigenetic mechanisms may play a major role in regulating expression of pro- or antinociceptive genes. DNA methylation is a major epigenetic mechanism in vertebrates, and methyl- CpG-binding protein 2 (MeCP2) is directly involved in methylation-mediated gene silencing. To determine how changes in global DNA methylation and MeCP2 expression occur following chronic constriction injury (CCI) and how repression of DNA methylation affects these changes and attenuates neuropathic pain, we used intrathecal 5-azacytidine, a DNA methyltransferase inhibitor, in CCI rats. Rats received 0.9% saline or 5-azacytidine (10µmol·d(-1)) via spinal injection once daily from day 3 to day 14 after CCI surgery. Global DNA methylation and MeCP2 expression increased in the spinal cord in CCI rats on day 14 after CCI surgery. Mechanical allodynia and thermal hyperalgesia induced by CCI were attenuated by intrathecal 5-azacytidine from day 5 to day 14 after CCI surgery. The increases in global DNA methylation and MeCP2 expression in the spinal cord in CCI rats were also significantly inhibited by intrathecal 5-azacytidine. These results demonstrate that increased global DNA methylation and MeCP2 expression in the spinal cord after nerve damage may play an important role in neuropathic pain. 5-azacytidine shows potential for treating neuropathic pain.
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Azacitidina/administração & dosagem , Metilação de DNA/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína 2 de Ligação a Metil-CpG/metabolismo , Neuralgia/tratamento farmacológico , Análise de Variância , Animais , Doença Crônica , Constrição Patológica/complicações , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lateralidade Funcional , Injeções Espinhais/métodos , Masculino , Proteína 2 de Ligação a Metil-CpG/genética , Neuralgia/etiologia , Medição da Dor , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Recent evidence suggests that P2X(3) receptors express abundantly in nociceptive sensory neurons and play an important role in neuropathic pain. Upregulation of prostaglandin E2 (PGE2) after nerve injure is involved in the pathogenesis of neuropathic pain. An increase of P2X(3) receptors after chronic constriction injury (CCI) to the sciatic nerve has also been reported, the mechanisms are not known clearly. In this study, we examined the effects of systemic administration of cyclooxygenase (COX) inhibitors on analgesia and the expression of P2X(3) receptors in the dorsal root ganglia (DRG) in CCI rats. Rats received 0.9% saline, the nonselective COX inhibitor ibuprofen (40mgkg(-1)day(-1)) or the selective COX-2 inhibitor celecoxib (30mgkg(-1)day(-1)) by gavage twice daily from 3 to 14 days after surgery. Mechanical allodynia and thermal hyperalgesia induced by CCI were markedly attenuated by celecoxib from 5 to 14 days after surgery, and relieved by ibuprofen treatment from 7 to 10 days after surgery. The increase of P2X(3) receptors in the DRG in CCI rats on day 14 after surgery was also significantly inhibited; the effect of ibuprofen was stronger than that of celecoxib. These results demonstrate that up-regulated COX/PGE2 after nerve damage may play an important role in neuropathic pain. They are highly involved in the expression of P2X(3) receptors in the DRG in CCI rats.