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1.
Adv Sci (Weinh) ; : e2405432, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39206821

RESUMEN

Genetic studies have identified the voltage-gated sodium channel 1.7 (Nav1.7) as pain target. Due to the ineffectiveness of small molecules and monoclonal antibodies as therapeutics for pain, single-domain antibodies (VHHs) are developed against the human Nav1.7 (hNav1.7) using a novel antigen presentation strategy. A 70 amino-acid peptide from the hNav1.7 protein is identified as a target antigen. A recombinant version of this peptide is grafted into the complementarity determining region 3 (CDR3) loop of an inert VHH in order to maintain the native 3D conformation of the peptide. This antigen is used to isolate one VHH able to i) bind hNav1.7, ii) slow the deactivation of hNav1.7, iii) reduce the ability of eliciting action potentials in nociceptors, and iv) reverse hyperalgesia in in vivo rat and mouse models. This VHH exhibits the potential to be developed as a therapeutic capable of suppressing pain. This novel antigen presentation strategy can be applied to develop biologics against other difficult targets such as ion channels, transporters and GPCRs.

2.
Biochem Biophys Res Commun ; 729: 150362, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38972142

RESUMEN

The therapeutic benefits of photobiomodulation (PBM) in pain management, although well documented, are accompanied by concerns about potential risks, including pain, particularly at higher laser intensities. This study investigated the effects of laser intensity on pain perception using behavioral and electrophysiological evaluations in rats. Our results show that direct laser irradiation of 1000 mW/cm2 to the sciatic nerve transiently increases the frequency of spontaneous firing in the superficial layer without affecting the deep layer of the spinal dorsal horn, and this effect reverses to pre-irradiation levels after irradiation. Interestingly, laser irradiation at 1000 mW/cm2, which led to an increase in spontaneous firing, did not prompt escape behavior. Furthermore, a significant reduction in the time to initiate escape behavior was observed only at 9500 mW/cm2 compared to 15, 510, 1000, and 4300 mW/cm2. This suggests that 1000 mW/cm2, the laser intensity at which an increase in spontaneous firing was observed, corresponds to a stimulus that did not cause pain. It is expected that a detailed understanding of the risks and mechanisms of PBM from a neurophysiological perspective will lead to safer and more effective use of PBM.


Asunto(s)
Terapia por Luz de Baja Intensidad , Ratas Sprague-Dawley , Asta Dorsal de la Médula Espinal , Animales , Terapia por Luz de Baja Intensidad/métodos , Masculino , Ratas , Asta Dorsal de la Médula Espinal/efectos de la radiación , Nervio Ciático/efectos de la radiación , Nervio Ciático/fisiología , Potenciales de Acción/efectos de la radiación
3.
Neurosci Res ; 198: 30-38, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37392833

RESUMEN

Repeated cold stress (RCS) can trigger the development of fibromyalgia (FM)-like symptoms, including persistent deep-tissue pain, although nociceptive changes to the skin have not been fully characterized. Using a rat RCS model, we investigated nociceptive behaviors induced by noxious mechanical, thermal, and chemical stimuli applied to plantar skin. Neuronal activation in the spinal dorsal horn was examined using the formalin pain test. In rats exposed to RCS, nociceptive behavioral hypersensitivity was observed in all modalities of cutaneous noxious stimuli: the mechanical withdrawal threshold was decreased, and the heat withdrawal latency was shortened one day after the cessation of stress. The duration of nocifensive behaviors in the formalin test was prolonged in phase II but not in phase I. The number of c-Fos-positive neurons increased in the entire dorsal horn laminae I-VI, ipsilateral, but not contralateral, to formalin injection at the L3-L5 segments. The duration of nocifensive behavior in phase II was significantly and positively correlated with the number of c-Fos-positive neurons in laminae I-II. These results demonstrate that cutaneous nociception is facilitated in rats exposed to RCS for a short time and that the spinal dorsal horn neurons are hyperactivated by cutaneous formalin in the RCS model.


Asunto(s)
Respuesta al Choque por Frío , Nocicepción , Ratas , Animales , Ratas Sprague-Dawley , Dimensión del Dolor/métodos , Dolor/metabolismo , Médula Espinal/metabolismo , Asta Dorsal de la Médula Espinal/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Formaldehído
4.
Math Biosci Eng ; 20(10): 17747-17782, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-38052535

RESUMEN

Modeling soil moisture as a function of meteorological data is necessary for agricultural applications, including irrigation scheduling. In this study, empirical water balance models and empirical compartment models are assessed for estimating soil moisture, for three locations in Colombia. The daily precipitation and average, maximum and minimum air temperatures are the input variables. In the water balance type models, the evapotranspiration term is based on the Hargreaves model, whereas the runoff and percolation terms are functions of precipitation and soil moisture. The models are calibrated using field data from each location. The main contributions compared to closely related studies are: i) the proposal of three models, formulated by combining an empirical water balance model with modifications in the precipitation, runoff, percolation and evapotranspiration terms, using functions recently proposed in the current literature and incorporating new modifications to these terms; ii) the assessment of the effect of model parameters on the fitting quality and determination of the parameters with higher effects; iii) the comparison of the proposed empirical models with recent empirical models from the literature in terms of the combination of fitting accuracy and number of parameters through the Akaike Information Criterion (AIC), and also the Nash-Sutcliffe (NS) coefficient and the root mean square error. The best models described soil moisture with an NS efficiency higher than 0.8. No single model achieved the highest performance for the three locations.

5.
Environ Sci Pollut Res Int ; 30(27): 70604-70620, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37155102

RESUMEN

Hotter and drier weather conditions due to climate change negatively affect water resources and agricultural production. For this reason, it is vital to analyze the change in potential evapotranspiration (PET) values, which is one of the most important parameters related to plant growth and agricultural irrigation planning. This study analyses the trends and changes in monthly and annual PET values between 1965 and 2018 at Erzincan, Bayburt and Gümüshane meteorological stations in Turkey. For this purpose, monotonic trends in PET values were determined by Spearman's rho (SR), Mann-Kendall (MK), Sen slope (SS), and innovative trend analysis (ITA) tests and change points were analyzed with the sequential MK (SQMK) test. The Hargreaves equation was used to calculate the PET values. As a result of the study, according to MK and SR tests, while increasing trends at 95% and 99% significance levels were dominant at Erzincan and Bayburt stations, no statistically significant trends were found at Gümüshane station except in February. ITA generally detected more than 5% increasing trends in PET data's low, medium, and high values. According to ITA slope analysis, there are significant increase trends in PET values at all periods, trend 1% significance level. According to the SQMK test, it was revealed that the trend started in PET values, especially in 1995, 2005, and 2010. The findings emphasized the importance of taking measures against decreased agricultural production and managing water resources effectively.


Asunto(s)
Cambio Climático , Tiempo (Meteorología) , Recursos Hídricos , Agricultura , Calor
6.
Neuroendocrinology ; 113(6): 667-677, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36796342

RESUMEN

INTRODUCTION: Differences in pain thresholds may have implications in pain management, as they may account in part for the variability in analgesic requirements between individuals. We planned to investigate the influence of endogenous sex hormones on the analgesic modulation of tramadol in lean and high-fat diet-induced obese Wistar rats. METHODS: The whole study was carried out on 48 adult Wistar rats (24 male: 12 obese and 12 lean and 24 female: 12 obese and 12 lean). Each male and female rat group was further subdivided into two groups (n = 6/group) and treated with normal saline/tramadol for 5 days. On the fifth day, 15 min after tramadol/normal saline treatment, animals were tested for pain perception toward noxious stimuli. Later, endogenous 17 beta-estradiol and free testosterone levels in serum were estimated through ELISA methods. RESULTS: The present study revealed that female rats experienced more pain sensitivity to noxious stimuli compared to male rats. High-fat diet-induced obese rats experienced more pain sensations to noxious stimuli than lean rats. Obese male rats were found to have significantly low free testosterone and high 17 beta-estradiol levels compared to lean male rats. An increase in serum 17 beta-estradiol level led to increased pain sensation to noxious stimuli. While an increase in free testosterone level resulted in the lowering of pain sensation to noxious stimuli. CONCLUSION: The analgesic effect of tramadol was more pronounced in male rats compared to female rats. The analgesic effect of tramadol was more marked in lean rats compared to obese rats. Additional research to elucidate obesity-induced endocrine changes and the mechanisms driving sex hormones in pain perception is needed to foster future interventions to reduce disparities in pain.


Asunto(s)
Tramadol , Ratas , Masculino , Femenino , Animales , Tramadol/farmacología , Tramadol/uso terapéutico , Ratas Wistar , Analgésicos Opioides/farmacología , Analgésicos Opioides/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Solución Salina/uso terapéutico , Dolor/tratamiento farmacológico , Dolor/etiología , Analgésicos/uso terapéutico , Hormonas Esteroides Gonadales , Estradiol/farmacología , Testosterona , Obesidad/tratamiento farmacológico
7.
Int J Mol Sci ; 23(19)2022 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-36233233

RESUMEN

Sigma-1 receptor (σ1R) ligands have been shown to be effective at relieving neuropathic and inflammatory pain, but have not yet been tested in experimental models of fibromyalgia. The objective of this study was to evaluate the effect of a σ1R antagonist (BD1063) compared to pregabalin. ICR-CD1 female mice were subjected to either six repeated injections of reserpine, to cause reserpine-induced myalgia (RIM6), or acidified saline intramuscular injections (ASI). In these two models, we evaluated the effect of BD1063 and pregabalin on thermal hypersensitivity, anxiety-like and depression-like behaviors, and on spinal cord gliosis. BD1063 exerted an antinociceptive effect on both reflexive (thermal hyperalgesia) and nonreflexive (anxiety- and depression-like) pain behaviors, and reduced spinal astroglial and microglial reactivity, following repeated treatment for 2 weeks. Interestingly, the effects of BD1063 were long-term, lasting several weeks after treatment discontinuation in both fibromyalgia-like models. Similar results were obtained with pregabalin, but the effects on pain behaviors lasted for a shorter length of time, and pregabalin did not significantly modulate spinal glial reactivity. The inhibitory and long-lasting effect of pharmacological blockade of σ1Rs on both sensory and affective dimensions of nociplastic-like pain and spinal cord gliosis in two experimental models of fibromyalgia support the application of this therapeutic strategy to treat fibromyalgia.


Asunto(s)
Analgésicos , Dolor Crónico , Fibromialgia , Receptores sigma , Analgésicos/uso terapéutico , Animales , Dolor Crónico/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Fibromialgia/tratamiento farmacológico , Gliosis , Hiperalgesia/tratamiento farmacológico , Ratones , Ratones Endogámicos ICR , Pregabalina/uso terapéutico , Receptores sigma/antagonistas & inhibidores , Reserpina/efectos adversos , Receptor Sigma-1
8.
PeerJ ; 9: e11571, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34178458

RESUMEN

Evapotranspiration carries vital importance in areas with arid and semi-arid climate properties for many issues, including the planning of irrigation water as a scarce resource, the establishment of irrigation programs and conducting project design for drainage. The empirical equations used for determining plant water consumption are classified subject to the diversity of the utilized data. The Penman-Monteith method used frequently in many parts of the world as a standard method needs more climate data. Models that yield results that are similar to those of the standard method with less climate parameters are preferred due to their ease of use and wide impact. Temperature, relative humidity and radiation data for the years 2008-2017 were utilized to analyze the usability of the Hargreaves-Samani and Turc-1961 equations with regard to the estimation of reference evapotranspiration in four provinces located in Southeastern Anatolia Region. Results obtained via models were compared in pairs by way of the standard method in order to define the performance of the models. While the best performances were obtained from the comparison with the standard method and Hargreaves-Samani value pair, the comparison of the standard model with Turc displayed the lowest performance. Based on the study data, ETo-Turc values were higher in the provinces analyzed, thus displaying a lower performance. While maximum long term annual monthly average ETo-HS value was identified as 7.6 mm at Diyarbakir in July, whereas the lowest value was determined at Kilis with 5.8 mm; the highest and lowest ETo-Turc values were obtained in the same month at Diyarbakir and Kilis with 13.3 and 10.3 mm respectively. It was calculated based on the long term average annual total ETo values that while highest ETo-HS was calculated at Diyarbakir with 1,500 mm, whereas the lowest value was calculated at Batman with 1,183 mm. The highest value for ETo-Turc was obtained at Diyarbakir with 2,365 mm while Mardin had the lowest ETo value with 1,920 mm. Accordingly, based on the ETo values calculated at both cities studies based on both models, Diyarbakir had the highest values, whereas Kilis had the lowest ETo values. According to the standard method known as PM, lowest daily ETo values were calculated in all provinces, which displayed the highest performance among the models. As a result of this study, it is possible to use the Hargreaves-Samani model instead of the standard model in the absence of reliable climatic data.

9.
Sensors (Basel) ; 20(6)2020 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-32245028

RESUMEN

Water use efficiency in agriculture can be improved by implementing advisory systems that support on-farm irrigation scheduling, with reliable forecasts of the actual crop water requirements, where crop evapotranspiration (ETc) is the main component. The development of such advisory systems is highly dependent upon the availability of timely updated crop canopy parameters and weather forecasts several days in advance, at low operational costs. This study presents a methodology for forecasting ETc, based on crop parameters retrieved from multispectral images, data from ground weather sensors, and air temperature forecasts. Crop multispectral images are freely provided by recent satellite missions, with high spatial and temporal resolutions. Meteorological services broadcast air temperature forecasts with lead times of several days, at no subscription costs, and with high accuracy. The performance of the proposed methodology was applied at 18 sites of the Campania region in Italy, by exploiting the data of intensive field campaigns in the years 2014-2015. ETc measurements were forecast with a median bias of 0.2 mm, and a median root mean square error (RMSE) of 0.75 mm at the first day of forecast. At the 5th day of accumulated forecast, the median bias and RMSE become 1 mm and 2.75 mm, respectively. The forecast performances were proved to be as accurate and as precise as those provided with a complete set of forecasted weather variables.

10.
Sci Total Environ ; 720: 137562, 2020 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-32325579

RESUMEN

This study reports the application of Soil and Water Assessment Tool (SWAT) within the Hydrologic and Water Quality System (HAWQS) on-line platform, for the Upper Mississippi River Basin (UMRB). The UMRB is an important ecosystem located in the north central U.S. that is experiencing a range of ecological stresses. Specifically, testing of SWAT was performed for: (1) Hargreaves (HG) and Penman-Monteith (PM) PET methods, and (2) Livneh, National Climatic Data Center (NCDC) and Parameter-elevation Regressions on Independent Slopes Model (PRISM) climate datasets. The Livneh-PM combination resulted in the highest average annual water yield of 380.6 mm versus the lowest estimated water yield of 193.9 mm for the Livneh-HG combination, in response to 23-year uncalibrated simulations. Higher annual ET and PET values were predicted with HG method versus the PM method for all three weather datasets in response to the uncalibrated simulations, due primarily to higher HG-based estimates during the growing season. Based on these results, it was found that the HG method is the preferred PET option for the UMRB. Initial calibration of SWAT was performed using the Livneh data and HG method for three Mississippi River main stem gauge sites, which was followed by spatial validation at 10 other gauge sites located within the UMRB stream network. Overall satisfactory results were found for the calibration and validation gauge sites, with the majority of R2 values ranging between 0.61 and 0.82, Nash-Sutcliffe modeling efficiency (NSE) values ranging between 0.50 and 0.79, and Kling-Gupta efficiency (KGE) values ranging between 0.61 and 0.84. The results of an additional experimental suite of six scenarios, which represented different combinations of climate data sets and calibrated parameters, revealed that suggested statistical criteria were again satisfied by the different scenario combinations. Overall, the PRISM data exhibited the strongest reliability for the UMRB.

11.
Biosci. j. (Online) ; 36(1): 17-22, jan./feb. 2020. ilus, tab
Artículo en Inglés | LILACS | ID: biblio-1049187

RESUMEN

The objective of this study was to verify the quality of the short-term forecasts made by some web sites, as well as the potential of its use in estimating reference evapotranspiration (ETo). For the period 2012-2013, every 4-days, the maximum (Tmax) and minimum (Tmin) air temperature forecasts for horizons of 24, 48, 72 and 96 hours provided by public sites for Uberlandia-MG were collected and used for calculating the reference evapotranspiration (ETo) by the Hargreaves-Samani (HS) calibrated equation. The sites www.accuweather.com (WEATHER); www.cemig.com.br (CEMIG); jornaldotempo.uol.com.br; (JORNAL) and www.climatempo.com.br (CLIMA) were evaluated. For the same period, the meteorological data were taken at the National Institute of Meteorology (www.inmet.gov.br). The performance of the Tmax and Tmin forecasts as well as the ETo estimates were made by regression analysis, the mean bias error (MBE), root mean square error (RMSE) and t-test. For all sites, there was a better performance in the prediction of Tmin when compared to Tmax, especially by a reduction in errors (MBE and RMSE) and an increase in coefficients b and R2. For ETo, the site CLIMA had lowest MBE and RMSE (0.9 mm d-1) following by the WEATHER and JORNAL. On the other hand, the site CEMIG presented higher values for MBE (-1.3 mm d-1) and RMSE (1.6 mm d-1). There was no worsening with an increase of the forecast horizon in these indices, except for R² values. The site CLIMA was the only one that did not differ significantly from the ETo values observed. The results of diagnostic verification procedures indicate the potential use of air temperature forecasts in irrigation management.


O objetivo deste trabalho foi verificar a qualidade das previsões de curto prazo feitas por alguns endereços eletrônicos da internet, bem como a potencialidade de seu uso na estimativa da evapotranspiração de referência (ETo). No período de 2012 a 2013, a cada quatro dias, foram coletadas as previsões de 24,48,72 e 96 de horizonte, da temperatura máxima (Tmax) e mínima (Tmin) do ar de quatro endereços eletrônicos para a cidade de Uberlândia, MG. Os dados previstos de temperatura, foram utilizados na equação calibrada do modelo de Hargreaves-Samani (HS) para a obtenção da estimativa da ETo. Os endereços avaliados foram: www.accuweather.com (WEATHER); www.cemig.com.br (CEMIG); jornaldotempo.uol.com.br; (JORNAL) e www.climatempo.com.br (CLIMA). No mesmo período, dados meteorológicos da cidade foram obtidos junto ao Instituto Nacional de Meteorologia (www.inmet.gov.br). A performance das previsões da temperatura e estimativas de ETo foram feitas por meio da análise de regressão, erro médio (EM), raiz quadrada do quadrado médio do erro (RQME) e pelo teste-t. Para todos os endereços, houve uma melhor performance na previsão da Tmin em relação a Tmax, especialmente pela redução dos erros (ME e RQME) e aumento nos coeficientes b e R2. Para ETo, o endereço CLIMA obteve os menores valores de EM e RQME (0,9 mm d-1) seguido do endereço WEATHER e JORNAL. Por outro lado, o endereço CEMIG apresentou os maiores valores para EM (-1,3 mm d-1) e RQME (1,6 mm d-1). Não houve piora na estimativa com aumento do horizonte de previsão nesses índices, exceto para R2. O endereço CLIMA foi o único que não diferiu significativamente dos valores de ETo observados. Os resultados de verificação indicam potencial uso das previsões para o manejo da irrigação.


Asunto(s)
Evapotranspiración , Predicción del Tiempo , Riego Agrícola
12.
Molecules ; 23(8)2018 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-30126223

RESUMEN

Atomoxetine is a selective noradrenaline reuptake inhibitor drug. Based on the knowledge that agents increasing monoamine levels in the central nervous system have therapeutic potential for neuropathic pain, it is planned to investigate the possible efficacy of atomoxetine on diabetes-induced hyperalgesia, in this study. Randall-Selitto (mechanical noxious stimuli) and Hargreaves (thermal noxious stimuli) tests were used to evaluate nociceptive perception of rats. Obtained data indicated that streptozotocin-induced diabetes causes significant decreases in the paw withdrawal threshold and paw withdrawal latency values of the animals, respectively. However, atomoxetine administered at 3 mg/kg/day for 7 and 14 days improved these diabetes-induced hyperalgesia responses. Furthermore, antihyperalgesic activity was antagonized with α-methyl-para-tyrosine methyl ester, phentolamine, propranolol, and sulpiride pre-treatments. The same effect was not reversed, however, by SCH 23390. These findings demonstrated, for the first time, that atomoxetine possesses significant antihyperalgesic activity on diabetes-induced neuropathic pain and this effect seems to be mediated by α- and ß-adrenergic and D2/D3 dopaminergic receptors. Results of this present study seem to offer a new indication for an old drug; atomoxetine, but these preclinical data should first be confirmed with further well-designed clinical trials.


Asunto(s)
Clorhidrato de Atomoxetina/farmacología , Catecolaminas/metabolismo , Neuropatías Diabéticas/complicaciones , Neuralgia/etiología , Neuralgia/metabolismo , Receptores de Catecolaminas/metabolismo , Animales , Modelos Animales de Enfermedad , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Masculino , Actividad Motora , Neuralgia/tratamiento farmacológico , Neuralgia/fisiopatología , Manejo del Dolor , Ratas
13.
Behav Brain Res ; 343: 21-27, 2018 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-29378294

RESUMEN

The experience of pain is characterized by the presence of a noxious sensory stimulus combined with negative affect, which is often treated clinically through administration of drugs such as morphine or other opioids. This study investigated the effects of morphine one and seven days after intraplantar administration of complete freund's adjuvant (CFA) in male and female rats. Hargreaves test for thermal nociception and conditioned place preference (CPP) were performed following subcutaneous administration of saline or morphine (1.0, 4.0, 8.0, 12.0 mg/kg). Hargreaves test results revealed that male rats were more sensitive to morphine antinociceptive actions as compared to female rats one day after CFA treatment; however, this sex difference was not detected seven days after CFA treatment. One day after CFA treatment, morphine doses of 8.0 and 12.0 mg/kg produced a CPP in male rats, while female rats exhibited CPP with only the 12.0 mg/kg dose. Seven days after CFA treatment, both male and female rats exhibited a CPP with morphine doses of 4.0 mg/kg and higher. These results reveal sexually dimorphic properties of morphine in the paw withdrawal latencies and conditioned place preference models, representing reflexive and non-reflexive behavioral assays employed to examine inflammatory nociception. Our findings also suggest that antinociceptive effects of morphine are dynamic across early and later periods of CFA-induced inflammatory pain.


Asunto(s)
Analgésicos/farmacología , Hiperalgesia/tratamiento farmacológico , Morfina/farmacología , Dolor Nociceptivo/tratamiento farmacológico , Conducta Espacial/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Femenino , Adyuvante de Freund , Calor , Hiperalgesia/fisiopatología , Inflamación/tratamiento farmacológico , Inflamación/fisiopatología , Masculino , Dolor Nociceptivo/fisiopatología , Ratas Sprague-Dawley , Reflejo/efectos de los fármacos , Reflejo/fisiología , Caracteres Sexuales , Conducta Espacial/fisiología
14.
Sleep ; 40(9)2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28934532

RESUMEN

Sleep and pain are reciprocally related, but the precise mechanisms underlying this relationship are poorly understood. This study used a rat model of surgical pain to examine the effect of previous sleep loss on postoperative pain and tested the hypothesis that preoptic adenosinergic mechanisms regulate sleep-pain interactions. Relative to ad libitum sleep, 6 hours of total sleep deprivation prior to a surgical incision significantly enhanced postoperative mechanical hypersensitivity in the affected paw and prolonged the time to recovery from surgery. There were no sex-specific differences in these measures. There were also no changes in adrenocorticotropic hormone and corticosterone levels after sleep deprivation, suggesting that this effect was not mediated by the stress associated with the sleep perturbation. Systemic administration of the nonselective adenosine receptor antagonist caffeine at the onset of sleep deprivation prevented the sleep deprivation-induced increase in postoperative hypersensitivity. Microinjection of the adenosine A2A receptor antagonist ZM 241385 into the median preoptic nucleus (MnPO) blocked the increase in surgical pain levels and duration caused by prior sleep deprivation and eliminated the thermal hyperalgesia induced by sleep deprivation in a group of nonoperated (i.e., without surgical incision) rats. These data show that even a brief sleep disturbance prior to surgery worsens postoperative pain and are consistent with our hypothesis that adenosine A2A receptors in the MnPO contribute to regulate these sleep-pain interactions.


Asunto(s)
Cafeína/administración & dosificación , Cafeína/farmacología , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Área Preóptica/efectos de los fármacos , Área Preóptica/metabolismo , Receptor de Adenosina A2A/metabolismo , Privación de Sueño/complicaciones , Antagonistas del Receptor de Adenosina A2/administración & dosificación , Antagonistas del Receptor de Adenosina A2/farmacología , Animales , Femenino , Hiperalgesia/etiología , Hiperalgesia/fisiopatología , Hiperalgesia/prevención & control , Masculino , Dolor Postoperatorio/fisiopatología , Ratas , Ratas Sprague-Dawley , Caracteres Sexuales , Sueño/fisiología , Privación de Sueño/fisiopatología , Triazinas/administración & dosificación , Triazinas/farmacología , Triazoles/administración & dosificación , Triazoles/farmacología
15.
Bio Protoc ; 7(16)2017 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-28920069

RESUMEN

The Hargreaves test is specifically designed to assess thermal pain sensation in rodents such as rats and mice. This test has been used in experiments involving pain sensitization or recovery of thermal pain response following neural injury and regeneration. We present here a step-by-step protocol highlighted with important notes to guide first-time users through the learning process. Additionally, we have also included representative data from a rat model of sensory denervation showing how the data can be analysed to obtain meaningful results. We hope that this protocol can also assist potential users in deciding whether the Hargreaves test is a suitable test for their experiment.

16.
Addict Biol ; 22(3): 692-701, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-26804193

RESUMEN

Humans diagnosed with alcohol use disorder are more sensitive to painful stimuli during withdrawal, which suggests that excessive alcohol drinking worsens pain outcomes. Alcohol-dependent rats exhibit increases in nociceptive sensitivity during withdrawal. Data from animal models suggest that brain melanocortin-4 receptors (MC4Rs) mediate alcohol drinking and nociception. Here we tested: (1) the effect of alcohol dependence on thermal nociception in rats, and (2) the ability of acute alcohol and (3) MC4R antagonists to reverse hyperalgesia during withdrawal in alcohol-dependent rats. Rats were trained to self-administer operant alcohol and were tested for baseline thermal nociception. Half of the rats were made dependent on alcohol, then all rats were cannulated in the lateral ventricle. We tested the effects of acute alcohol drinking, acute fixed-dose alcohol, intra-ventricular agouti-related protein (endogenous MC4R antagonist), intra-ventricular HS014 (synthetic MC4R antagonist) and intra-nasal HS014 on hyperalgesia during withdrawal in alcohol-dependent rats, relative to non-dependent drinkers and alcohol-naïve controls. Alcohol-dependent rats exhibit thermal hyperalgesia that is abolished by alcohol drinking, bolus alcohol and intra-ventricular and intra-nasal MC4R antagonists. These manipulations did not affect thermal nociception in non-dependent drinkers and alcohol-naïve controls, suggesting that alcohol dependence produces neuroadaptations in brain MC4R systems. These results suggest that brain MC4R systems may be an effective therapeutic target for reducing nociception in the alcohol-dependent organism.


Asunto(s)
Alcoholismo/complicaciones , Encéfalo/efectos de los fármacos , Hiperalgesia/tratamiento farmacológico , Péptidos Cíclicos/farmacología , Receptor de Melanocortina Tipo 4/antagonistas & inhibidores , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Administración Intranasal , Animales , Modelos Animales de Enfermedad , Hiperalgesia/complicaciones , Masculino , Nocicepción/efectos de los fármacos , Ratas Wistar
17.
BMC Anesthesiol ; 16(1): 73, 2016 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-27596139

RESUMEN

BACKGROUND: Nerve growth factor (NGF) is known to induce inflammation and pain; however its role in opioid-induced tolerance has not been studied. This study investigated the effects of an anti-NGF neutralizing antibody on the development of tolerance following chronic morphine treatment in naïve rats. METHODS: Four groups of rats were used in this study; one treated with saline alone, one with 10 mg/kg of morphine, one with 10 µg of anti-NGF and the other with 10 mg/kg of morphine + 10 µg of anti-NGF, twice per day for 5 days. The route of treatment was subcutaneous (S.C.) for morphine and saline, and intraperitoneal (i.p.) for anti-NGF. Response to a noxious thermal stimulus during the course of drug treatment was assessed (Hargreaves' test). Further, the change in the NGF levels in the lumbar spinal cord was measured by ELISA. RESULTS: Our results showed that repeated administration of morphine produced an apparent tolerance which was significantly attenuated by co-administration of anti-NGF (P < 0.001). Additionally, the area under the curve (AUC) of the analgesic effect produced by the combination of morphine and anti-NGF was significantly (P < 0.001) greater than for saline controls and chronic morphine treated rats. Moreover, the level of NGF in the spinal cord of chronic morphine treated rats was significantly higher (P < 0.05) than in both the saline control group and the group receiving simultaneous administration of anti-NGF with morphine. These results indicate that anti-NGF has the potential to attenuate morphine-induced tolerance behavior by attenuating the effects of NGF at the spinal level. CONCLUSION: Taken together, our study strongly suggests that the NGF signaling system is a potential novel target for treating opioid-induced tolerance.


Asunto(s)
Anticuerpos Neutralizantes/farmacología , Tolerancia a Medicamentos/inmunología , Morfina/inmunología , Factor de Crecimiento Nervioso/inmunología , Administración Cutánea , Animales , Anticuerpos Neutralizantes/administración & dosificación , Inyecciones Intraperitoneales , Masculino , Morfina/administración & dosificación , Morfina/farmacología , Factor de Crecimiento Nervioso/metabolismo , Dimensión del Dolor/efectos de los fármacos , Ratas , Médula Espinal/metabolismo
18.
Sleep ; 39(1): 133-42, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-26237772

RESUMEN

STUDY OBJECTIVES: Insufficient sleep and chronic pain are public health epidemics. Sleep loss worsens pain and predicts the development of chronic pain. Whether previous, acute sleep loss and recovery sleep determine pain levels and duration remains poorly understood. This study tested whether acute sleep deprivation and recovery sleep prior to formalin injection alter post-injection pain levels and duration. METHODS: Male Sprague-Dawley rats (n = 48) underwent sleep deprivation or ad libitum sleep for 9 hours. Thereafter, rats received a subcutaneous injection of formalin or saline into a hind paw. In the recovery sleep group, rats were allowed 24 h between sleep deprivation and the injection of formalin. Mechanical and thermal nociception were assessed using the von Frey test and Hargreaves' method. Nociceptive measures were performed at 1, 3, 7, 10, 14, 17 and 21 days post-injection. RESULTS: Formalin caused bilateral mechanical hypersensitivity (allodynia) that persisted for up to 21 days post-injection. Sleep deprivation significantly enhanced bilateral allodynia. There was a synergistic interaction when sleep deprivation preceded a formalin injection. Rats allowed a recovery sleep period prior to formalin injection developed allodynia only in the injected limb, with higher mechanical thresholds (less allodynia) and a shorter recovery period. There were no persistent changes in thermal nociception. CONCLUSION: The data suggest that acute sleep loss preceding an inflammatory insult enhances pain and can contribute to chronic pain. The results encourage studies in a model of surgical pain to test whether enhancing sleep reduces pain levels and duration.


Asunto(s)
Dolor Crónico/complicaciones , Dolor Crónico/fisiopatología , Inflamación/complicaciones , Privación de Sueño/complicaciones , Privación de Sueño/fisiopatología , Sueño/fisiología , Animales , Dolor Crónico/diagnóstico , Formaldehído , Hiperalgesia/inducido químicamente , Hiperalgesia/complicaciones , Inflamación/inducido químicamente , Masculino , Dimensión del Dolor , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
19.
Environ Monit Assess ; 187(11): 699, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26497559

RESUMEN

In arid northwestern China, water shortages have triggered recent regulations affecting irrigation water use in desert-oasis agricultural systems. In order to determine the actual water demand of various crops and to develop standards for the rational use of water resources, we analyzed meteorological data from the Fukang desert ecosystem observation and experiment station (FKD), the Cele desert-grassland ecosystem observation and research station (CLD), and the Linze Inland River Basin Comprehensive Research Station (LZD), which all belong to the Chinese Ecosystem Research Network. We researched crop evapotranspiration (ETc) using the water balance method, the FAO-56 Penman-Monteith method, the Priestley-Taylor method, and the Hargreaves method, during the growing seasons of 2005 through 2009. Results indicate substantial differences in ETc, depending on the method used. At the CLD, the ETc from the soil water balance, FAO-56 Penman-Monteith, Priestley-Taylor, and Hargreaves methods were 1150.3±380.8, 783.7±33.6, 1018.3±22.1, and 611.2±23.3 mm, respectively; at the FKD, the corresponding results were 861.0±67.0, 834.2±83.9, 1453.5±47.1, and 1061.0±38.2 mm, respectively; and at the LZD, 823.4±110.4, 726.0±0.4, 722.3±29.4, and 1208.6±79.1 mm, respectively. The FAO-56 Penman-Monteith method provided a fairly good estimation of E Tc compared with the Priestley-Taylor and Hargreaves methods.


Asunto(s)
Riego Agrícola/métodos , Productos Agrícolas/crecimiento & desarrollo , Agricultura , China , Ecosistema , Monitoreo del Ambiente , Transpiración de Plantas , Ríos , Estaciones del Año , Suelo , Agua
20.
Behav Brain Res ; 278: 193-201, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25300472

RESUMEN

Chronic pain and depression share a complex, reciprocal relationship. Furthermore, in addition to treating depression, antidepressants such as amitriptyline are a first-line treatment for chronic pain conditions, indicating possible common neural substrates underlying both depression and pain. However, there is a paucity of studies examining the effect of antidepressant treatment on nociceptive and neuropathic pain responding in the presence of a depressive phenotype. The current study aimed to examine the effect of chronic amitriptyline administration on neuropathic pain-related behaviour and associated neuroinflammatory processes in the olfactory bulbectomised (OB) rat model of depression. Nociceptive responding to mechanical, innocuous cold or noxious heat stimuli in sham or OB rats was not altered by chronic amitriptyline administration. The induction of neuropathic pain following L5-L6 spinal nerve ligation (SNL) resulted in robust mechanical and cold allodynia and heat hyperalgesia in both sham and OB vehicle-treated animals. Chronic amitriptyline administration attenuated SNL-induced mechanical allodynia in both sham and OB rats at day 7 post-SNL, an effect which was enhanced and prolonged in OB rats. In comparison, chronic amitriptyline administration attenuated SNL-induced cold allodynia and heat hyperalgesia in sham, but not OB, rats. Evaluating the affective/motivational aspect of pain using the place escape avoidance paradigm revealed that OB-SNL rats exhibit reduced noxious avoidance behaviour when compared with sham counterparts, an effect not altered by chronic amitriptyline administration. Chronic amitriptyline administration prevented the increased expression of GFAP, IL-10 and CCL5, and enhanced the expression of TNFα, in the prefrontal cortex of OB-SNL rats. In conclusion, these data demonstrate that chronic amitriptyline differentially alters somatic nociceptive responding following peripheral nerve-injury, depending on stimulus modality and the presence or absence of a depressive-like phenotype, an effect which may involve modulation of neuroinflammatory processes.


Asunto(s)
Amitriptilina/farmacología , Antidepresivos Tricíclicos/farmacología , Depresión/psicología , Neuralgia/tratamiento farmacológico , Corteza Prefrontal/inmunología , Amitriptilina/administración & dosificación , Animales , Antidepresivos Tricíclicos/administración & dosificación , Depresión/fisiopatología , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/metabolismo , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/inmunología , Hiperalgesia/psicología , Interleucina-10/metabolismo , Masculino , Neuralgia/inmunología , Neuralgia/psicología , Dimensión del Dolor/métodos , Traumatismos de los Nervios Periféricos/complicaciones , Fenotipo , Ratas , Ratas Sprague-Dawley , Nervios Espinales/cirugía , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo
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