Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

Nerve injury leads to a neuropathic pain state that results from central sensitization. This phenomenom is mediated by NMDA receptors and may involve the production of nitric oxide (NO). In this study, we investigated the expression of the neuronal isoform of NO synthase (nNOS) in the spinal cord of 3-month-old male, Wistar rats after sciatic nerve transection (SNT). Our attention was focused on the dorsal part of L3-L5 segments receiving sensory inputs from the sciatic nerve. SNT resulted in the development of neuropathic pain symptoms confirmed by evaluating mechanical hyperalgesia (Randall and Selitto test) and allodynia (von Frey hair test). Control animals did not present any alteration (sham-animals). The selective inhibitor of nNOS, 7-nitroindazole (0.2 and 2 µg in 50 µL), blocked hyperalgesia and allodynia induced by SNT. Immunohistochemical analysis showed that nNOS was increased (48% by day 30) in the lumbar spinal cord after SNT. This increase was observed near the central canal (Rexed’s lamina X) and also in lamina I-IV of the dorsal horn. Real-time PCR results indicated an increase of nNOS mRNA detected from 1 to 30 days after SNT, with the highest increase observed 1 day after injury (1469%). Immunoblotting confirmed the increase of nNOS in the spinal cord between 1 and 15 days post-lesion (20%), reaching the greatest increase (60%) 30 days after surgery. The present findings demonstrate an increase of nNOS after peripheral nerve injury that may contribute to the increase of NO production observed after peripheral neuropathy.

Purinergic signalling: past, present and future

The discovery of non-adrenergic, non-cholinergic neurotransmission in the gut and bladder in the early 1960's is described as well as the identification of adenosine 5'-triphosphate (ATP) as a transmitter in these nerves in the early 1970's. The concept of purinergic cotransmission was formulated in 1976 and it is now recognized that ATP is a cotransmitter in all nerves in the peripheral and central nervous systems. Two families of receptors to purines were recognized in 1978, P1 (adenosine) receptors and P2 receptors sensitive to ATP and adenosine diphosphate (ADP). Cloning of these receptors in the early 1990's was a turning point in the acceptance of the purinergic signalling hypothesis and there are currently 4 subtypes of P1 receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of G protein-coupled receptors. Both short-term purinergic signalling in neurotransmission, neuromodulation and neurosecretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation, motility, death in development and regeneration are recognized. There is now much known about the mechanisms underlying ATP release and extracellular breakdown by ecto-nucleotidases. The recent emphasis on purinergic neuropathology is discussed, including changes in purinergic cotransmission in development and ageing and in bladder diseases and hypertension. The involvement of neuron-glial cell interactions in various diseases of the central nervous system, including neuropathic pain, trauma and ischemia, neurodegenerative diseases, neuropsychiatric disorders and epilepsy are also considered.

Expression of Fos protein in the rat central nervous system in response to noxious stimulation: effects of chronic inflammation of the superior cervical ganglion

The aim of this study was to investigate the possible interactions between the nociceptive system, the sympathetic system and the inflammatory process. Thus, the superior cervical ganglion of rats was submitted to chronic inflammation and Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. The painful stimulus consisted of subcutaneously injected formalin applied to the supra-ocular region. Fos-positive neurons were identified by conventional immunohistochemical techniques, and analyzed from the obex through the cervical levels of the spinal cord. In the caudal sub-nucleus of the spinal trigeminal nuclear complex, the number of Fos-positive neurons was much higher in rats with inflammation of the superior cervical ganglion than in control rats, either sham-operated or with saline applied to the ganglion. There was a highly significant difference in the density of Fos-positive neurons between the inflamed and control groups. No significant difference was found between control groups. These results suggest that the inflammation of the superior cervical ganglion generated an increased responsiveness to painful stimuli, which may have been due to a diminished sympathetic influence upon the sensory peripheral innervation.

Antinociceptive potency of aminoglycoside antibiotics and magnesium chloride: a comparative study on models of phasic and incisional pain in rats

A close relationship exists between calcium concentration in the central nervous system and nociceptive processing. Aminoglycoside antibiotics and magnesium interact with N- and P/Q-type voltage-operated calcium channels. In the present study we compare the antinociceptive potency of intrathecal administration of aminoglycoside antibiotics and magnesium chloride in the tail-flick test and on incisional pain in rats, taken as models of phasic and persistent post-surgical pain, respectively. The order of potency in the tail-flick test was gentamicin (ED50 = 3.34 µg; confidence limits 2.65 and 4.2) > streptomycin (5.68 µg; 3.76 and 8.57) = neomycin (9.22 µg; 6.98 and 12.17) > magnesium (19.49 µg; 11.46 and 33.13). The order of potency to reduce incisional pain was gentamicin (ED50 = 2.06 µg; confidence limits 1.46 and 2.9) > streptomycin (47.86 µg; 26.3 and 87.1) = neomycin (83.17 µg; 51.6 and 133.9). The dose-response curves for each test did not deviate significantly from parallelism. We conclude that neomycin and streptomycin are more potent against phasic pain than against persistent pain, whereas gentamicin is equipotent against both types of pain. Magnesium was less potent than the antibiotics and effective in the tail-flick test only.

Central release of nitric oxide mediates antinociception induced by aerobic exercise

Nitric oxide (NO) is a soluble gas that participates in important functions of the central nervous system, such as cognitive function, maintenance of synaptic plasticity for the control of sleep, appetite, body temperature, neurosecretion, and antinociception. Furthermore, during exercise large amounts of NO are released that contribute to maintaining body homeostasis. Besides NO production, physical exercise has been shown to induce antinociception. Thus, the present study aimed to investigate the central involvement of NO in exercise-induced antinociception. In both mechanical and thermal nociceptive tests, central [intrathecal (it) and intracerebroventricular (icv)] pretreatment with inhibitors of the NO/cGMP/KATP pathway (L-NOArg, ODQ, and glybenclamide) prevented the antinociceptive effect induced by aerobic exercise (AE). Furthermore, pretreatment (it, icv) with specific NO synthase inhibitors (L-NIO, aminoguanidine, and L-NPA) also prevented this effect. Supporting the hypothesis of the central involvement of NO in exercise-induced antinociception, nitrite levels in the cerebrospinal fluid increased immediately after AE. Therefore, the present study suggests that, during exercise, the NO released centrally induced antinociception.

Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

A efetividade do treinamento auditivo na desordem do processamento auditivo central: estudo de caso

O objetivo deste trabalho é a apresentação de um caso de um indivíduo de 9 anos de idade, do sexo masculino, com queixa de distúrbio de aprendizagem, para o qual a efetividade da fonoterapia pôde ser avaliada através de testes objetivos e comportamentais, compreendendo audiometria tonal, imitanciometria, potenciais auditivos evocados de tronco encefálico, P300 e Avaliação do Processamento Auditivo Central. Foram encontrados resultados normais nos exames otorrinolaringológico e audiológico. O P300 foi realizado mostrando tempo de latência aumentada. A avaliação do Processamento Auditivo Central revelou uma desordem em grau severo, caracterizada por alterações nos processos de codificação, organização e memória, assim como dificuldade significativa para atenção seletiva e fechamento auditivo. Foi diagnosticado Desordem do Processamento Auditivo Central, sendo que o indivíduo foi encaminhado para acompanhamento fonoaudiológico com o objetivo de desenvolvimento das habilidades auditivas alteradas. Após um período de 4 meses de fonoterapia, repetidos os exames acima descritos, observou-se melhora nas latências do P300, a desordem permaneceu em grau moderado, com prejuízo mais significativo no processo de organização e não apresentou dificuldade para o fechamento auditivo. Podemos concluir com este estudo a efetividade da terapia fonoaudiológica para o desenvolvimento das habilidades auditivas, podendo ser verificada através da avaliação objetiva e comportamental.

Vertigem como manifestação isolada de desmielinização no sistema nervoso central: relato de caso e revisão de literatura

A vertigem é um sintoma responsável por um grande número de visitas aos consultórios de médicos de diversas especialidades. Dessa forma, um conhecimento apropriado sobre sua etiologia e fisiopatologia possíveis é extremamente importante. Apresentamos um caso clínico que ilustra o conjunto de possibilidades etiológicas para este sintoma e a importância da completa avaliação do paciente, sempre valorizando suas queixas.

O Mismatch Negativity em pacientes com distúrbios do processamento auditivo (central)

O Mismatch Negativity (MMN) é um potencial evocado auditivo de longa latência que fornece uma medida objetiva das habilidades de discriminação e memória sensorial auditiva. Assim, pode ser utilizado como uma avaliação eletrofisiológica do processamento auditivo (central). OBJETIVO: Estudar o MMN em pacientes com Distúrbios do Processamento Auditivo (Central) - DPA(C). FORMA DO ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: Foram avaliados oito sujeitos com DPA(C), na faixa etária de nove a 14 anos, bem como um grupo controle. O MMN foi eliciado para estímulos tonais (tone bursts) diferindo quanto à freqüência (MMNf - estímulo padrão: 750Hz e estímulo diferente: 1000Hz ), bem como quanto à duração (MMNd - estímulo padrão: 100 ms e estímulo diferente: 50 ms; na freqüência de 1000Hz). RESULTADOS: A presença do MMNf e do MMNd foi comprovada estatisticamente em ambos os grupos estudados. Não foram constatadas diferenças significantes estatisticamente entre os valores de latência e de amplitude do MMNf e do MMNd obtidos nos dois grupos. Também não foram verificadas diferenças significantes estatisticamente entre o MMNf e o MMNd em nenhum dos grupos estudados. CONCLUSÃO: Os sujeitos com DPA(C) avaliados não apresentaram alterações no MMNf, nem no MMNd.

O Brasil frente ao conflito regional na América Central: oposição ao intervencionismo e apoio à solução negociada, justa, equilibrada e duradoura (1979-1996)

O artigo analisa alguns aspectos da percepção brasileira sobre o conflito regional imperante na América Central, entre 1979 e 1996. Na conclusão sugere-se que essa política fundamentou-se no que aqui se chama de a "tese brasileira" sobre a origem, a evolução e os possíveis mecanismos de resolução para o conflito regional.

Soil profile internal drainage for a central pivot fertigated coffee crop

Coffee cultivation via central-pivot fertigation can lead to fertilizer losses by soil profile internal drainage when water application is excessive and soils have low water retention and cation adsorption capacities. This study analyses the deep water losses from the top 1 m sandy soil layer of east Bahia, Brazil, cultivated with coffee at a high technology level (central-pivot fertigation), using above normal N fertilizer rates. The deep drainage (Q) estimation is made through the application of a climatologic water balance (CWB) program having as input direct measures of irrigation and rainfall, climatological data from weather stations, and measured soil water retention characteristics. The aim of the study is to contribute to the understanding of the hydric regime of coffee crops managed by central-pivot irrigation, analyzing three scenarios (Sc): i) rainfall only, ii) rainfall and irrigation full year, and iii) rainfall and irrigation dry season only. Annual Q values for the 2008/2009 agricultural year were: Sc i = 811.5 mm; Sc ii = 1010.5 mm; and Sc iii = 873.1 mm, so that the irrigation interruption in the wet season reduced Q by 15.7%, without the appearance of water deficit periods. Results show that the use of the CWB program is a convenient tool for the evaluation of Q under the cited conditions.

Nitrogen fertilizer (15N) leaching in a central pivot fertigated coffee crop

Nitrogen has a complex dynamics in the soil-plant-atmosphere system. N fertilizers are subject to chemical and microbial transformations in soils that can result in significant losses. Considering the cost of fertilizers, the adoption of good management practices like fertigation could improve the N use efficiency by crops. Water balances (WB) were applied to evaluate fertilizer N leaching using 15N labeled urea in west Bahia, Brazil. Three scenarios (2008/2009) were established: i) rainfall + irrigation the full year, ii) rainfall only; and iii) rainfall + irrigation only in the dry season. The water excess was considered equal to the deep drainage for the very flat area (runoff = 0) with a water table located several meters below soil surface (capillary rise = 0). The control volume for water balance calculations was the 0 - 1 m soil layer, considering that it involves the active root system. The water drained below 1 m was used to estimate fertilizer N leaching losses. WB calculations used the mathematic model of Penman-Monteith for evapotranspiration, considering the crop coefficient equal to unity. The high N application rate associated to the high rainfall plus irrigation was found to be the main cause for leaching, which values were 14.7 and 104.5 kg ha-1 for the rates 400 and 800 kg ha-1 of N, corresponding to 3.7 and 13.1 % of the applied fertilizer, respectively.

Juvenile tree growth correlates with photosynthesis and leaf phosphorus content in central Amazonia

Light and soil water availability may limit carbon uptake of trees in tropical rainforests. The objective of this work was to determine how photosynthetic traits of juvenile trees respond to variations in rainfall seasonality, leaf nutrient content, and opening of the forest canopy. The correlation between leaf nutrient content and annual growth rate of saplings was also assessed. In a terra firme rainforest of the central Amazon, leaf nutrient content and gas exchange parameters were measured in five sapling tree species in the dry and rainy season of 2008. Sapling growth was measured in 2008 and 2009. Rainfall seasonality led to variations in soil water content, but it did not affect leaf gas exchange parameters. Subtle changes in the canopy opening affected CO2 saturated photosynthesis (A pot, p = 0.04). Although A pot was affected by leaf nutrient content (as follows: P > Mg > Ca > N > K), the relative growth rate of saplings correlated solely with leaf P content (r = 0.52, p = 0.003). At present, reduction in soil water content during the dry season does not seem to be strong enough to cause any effect on photosynthesis of saplings in central Amazonia. This study shows that leaf P content is positively correlated with sapling growth in the central Amazon. Therefore, the positive effect of atmospheric CO2 fertilization on long-term tree growth will depend on the ability of trees to absorb additional amount of P