Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons.

BACKGROUND: Hydrogen sulfide (H2S), an endogenous gaseotransmitter/modulator, is becoming appreciated that it may be involved in a wide variety of processes including inflammation and nociception. However, the role and mechanism for H2S in nociceptive processing in trigeminal ganglion (TG) neuron remains unknown. The aim of this study is to investigate distribution of endogenous H2S synthesizing enzyme cystathionine-ß-synthetase (CBS) expression and role of H2S on excitability and voltage-gated potassium channels of TG neurons. METHODS: Immunofluorescence studies were carried out to determine whether CBS was co-expressed in Kv1.1 or Kv1.4-positive TG neurons. Whole cell patch clamp recordings were employed on acutely isolated TG neurons from adult male Sprague Dawley rats (6-8 week old). von Frey filaments were used to examine the pain behavioral responses in rats following injection of sodium hydrosulfide. RESULTS: In rat TG, 77.3±6.6% neurons were immunoreactive for CBS, 85.1±3.8% for Kv1.1 and 97.8±1.1% for Kv1.4. Double staining showed that all CBS labeled cells were Kv1.1 and Kv1.4 positive, but only 92.2±6.1% of Kv1.1 and 78.2±9.9% of Kv1.4 positive cells contained CBS. Application of H2S donor NaHS (250 µM) led to a significant depolarization of resting membrane potential recorded from TG neurons. NaHS application also resulted in a dramatic reduction in rheobase, hyperpolarization of action potential threshold, and a significant increase in the number of action potentials evoked at 2X and 3X rheobase stimulation. Under voltage-clamp conditions, TG neurons exhibited transient A-type (IA) and sustained outward rectifier K+ currents (IK). Application of NaHS did suppress IK density while did not change IA density of TG neurons (n=6). Furthermore, NaHS, a donor of hydrogen sulfide, produced a significant reduction in escape threshold in a dose dependent manner. CONCLUSION: These data suggest that endogenous H2S generating enzyme CBS was co-localized well with Kv1.1 and Kv1.4 in TG neurons and that H2S produces the mechanic pain and increases neuronal excitability, which might be largely mediated by suppressing IK density, thus identifying for the first time a specific molecular mechanism underlying pain and sensitization in TG.

[Non-linear registration of MR brain images integrated with machine learning].

This paper presents a machine learning method to select best geometric features for deformable brain registration for each brain location. By incorporating those learned best attribute vector into the framework of HAMMER registration algorithm, The accuracy has increased by about 10% in estimating the simulated deformation fields. At the same time, on real MR brain images, we have found a great deal of improvement of registration in cortical regions.

[An approach to adaptive stereo brain image's segmentation].

This paper presents a new method for automatically segmenting brain parenchyma and cerebrospinal fluid in routine single-echo MR images. This method is based on the coupled Markov models. They can model intensity measurement at each voxel site to implement piecewise smoothness constraint, and at the same time, model discontinuities to control the interaction between each pair of the neighboring voxel. The method is to derive the maximum a posteriori estimate of the regions and the boundaries by using Bayesian inference and neighborhood constraints based on Markov random fields (MRFs) models. This method has the following desirable properties: (1) the brain image can be well classified into white matter, grey matter and cerebrospinal fluid (CSF), and (2) it has a better robustness to noise and intensity inhomogeneity.

[Multi-target extraction algorithm based on edge restriction and attraction field regularization].

The topologically-adaptable model is an effective method for the contour detection of multiple objects on an image. However, it meets many problems when we apply it to MR brain images, such as poor convergence to boundary concavities, resulting from the broken boundary, and miserable anti-noise ability. In this paper, we proposes a new algorithm, named multi-target extraction algorithm based on edge restriction and attraction field regularization, to overcome these shortcomings. This new algorithm uses prior knowledge about target to perform edge restriction to get the only edge of the object of interest and to regularize attraction field to enlarge attraction field. Results show that the new algorithm can extract the target contour quickly and accurately when we apply it in MR brain images.

[Segmenting lung fields in serial chest radiographs using both population and patient-specific shape statistics].

This paper presents a new deformable model using both population-based and patient-specific shape statistics to segment lung fields from serial chest radiographs. First, a modified scale-invariant feature transform (SIFT) local descriptor is used to characterize the image features in the vicinity of each pixel, so that the deformable model deforms in a way that seeks for the region with similar SIFT local descriptors; second, the deformable model is constrained by both population-based and patient-specific shape statistics. At first, population-based shape statistics plays an leading role when the number of serial images is small, and gradually, patient-specific shape statistics plays a more and more important role after a sufficient number of segmentation results on the same patient have been obtained. The proposed deformable model can adapt to the shape variability of different patients, and obtain more robust and accurate segmentation results.

Targeting voltage-gated sodium channels for treatment for chronic visceral pain.

Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability, and their abnormal activity is related to several pathological processes, including cardiac arrhythmias, epilepsy, neurodegenerative diseases, spasticity and chronic pain. In particular, chronic visceral pain, the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome, is a serious clinical problem that affects a high percentage of the world population. In spite of intense research efforts and after the dedicated decade of pain control and research, there are not many options to treat chronic pain conditions. However, there is a wealth of evidence emerging to give hope that a more refined approach may be achievable. By using electronic databases, available data on structural and functional properties of VGSCs in chronic pain, particularly functional gastrointestinal hypersensitivity, were reviewed. We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functional gastrointestinal disorders. We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases, and outline future developments that may extend the therapeutic use of compounds that target VGSCs. Overall, clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.