Defining the Functional Expression of TRPV4 in Sensory Ganglia and the Gastrointestinal Tract

Transient Receptor Potential Vanilloid 4 (TRPV4) is a widely expressed sensory protein activated by diverse stimuli ranging from mechanical stress to inflammatory lipids and heat. Current research focuses predominantly on how TRPV4 expressed by nerve cells contributes to pain and inflammation. Using fine dissection techniques and imaging based methods, we identified TRPV4 expression by numerous non-neuronal cells, both surrounding pain sensing nerve cells, and in the gut. Thus, many processes considered as originating from nerve cells possibly initiate from non-neuronal cells. The findings of this thesis have major implications for drug discovery, and for our understanding of TRPV4-mediated cellular processes

haesleinhuepf/napari-workflows: 0.2.10

<h2>What's Changed</h2> <ul> <li>Bugfix filenames turned into image names by @haesleinhuepf in https://github.com/haesleinhuepf/napari-workflows/pull/37</li> </ul> <p><strong>Full Changelog</strong>: https://github.com/haesleinhuepf/napari-workflows/compare/0.2.9...0.2.10</p&gt

Data on comparative studies of lineaments extraction from ASTER DEM, SRTM, and Cartosat for Jilledubanderu River basin, Anantapur district, A.P, India by using remote sensing and GIS

The data deals with the functions that automatically extracted lineaments from the Cartosat, ASTER and SRTM of Digital Elevation Model (DEM) of different spatial resolutions, in the software ArcGIS 10.4. The extracted lineaments result shows the ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) DEM gives the lowest number of lineaments reflects Cartosat and SRTM (Shuttle Radar Topography Mission) DEM shows a medium number of lineaments. Cartosat DEM is most appropriate for extraction of contours precisely rather than ASTER and SRTM. This study reveals the Cartosat DEM data is best to use extraction of lineaments in the Indian provinces, offers at most comprehensive geological structural info amongst all the data sets. The extracted lineaments lengths and densities are determined by the statistical method. Based on the data generated lineament density and rose diagram. Cartosat DEM data are the best suited for studying very small areas as through geological and structural information can be mined by using this data. Abbreviations: DEM Digital Elevation Model, SRTM Shuttle Radar Topography Mission, ASTER Advanced Spaceborne Thermal Emission and Reflection Radiometer, Keywords: ASTER-DEM, SRTM, Cartosat DEM, Lineaments, Rose diagram, Extractio

Granulocyte-macrophage colony stimulating factor as an indirect mediator of nociceptor activation and pain

The interaction between the immune system and the nervous system has been at the centre of multiple research studies in recent years. While the role played by cytokines as neuronal mediators is no longer contested, the mechanisms by which cytokines modulate pain processing remain to be elucidated. In this study, we have analysed the involvement of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in nociceptor activation in male and female mice. Previous studies have suggested GM-CSF might directly activate neurons. However, here we established the absence of a functional GM-CSF receptor in murine nociceptors, and suggest an indirect mechanism of action, via immune cells. We report that GM-CSF applied directly to magnetically purified nociceptors does not induce any transcriptional changes in nociceptive genes. In contrast, conditioned medium from GM-CSF-treated murine macrophages was able to drive nociceptor transcription. We also found that conditioned medium from nociceptors treated with the well-established pain mediator, Nerve Growth Factor (NGF), could also modify macrophage gene transcription, providing further evidence for a bidirectional crosstalk.SIGNIFICANCE STATEMENTThe interaction of the immune system and the nervous system is known to play an important role in the development and maintenance of chronic pain disorders. Elucidating the mechanisms of these interactions is an important step towards understanding, and therefore treating, chronic pain disorders. This study provides evidence for a two-way cross talk between macrophages and nociceptors in the peripheral nervous system which may contribute to the sensitization of nociceptors by cytokines in pain development

Mu and Delta Opioid Receptors Are Coexpressed and Functionally Interact in the Enteric Nervous System of the Mouse Colon

BACKGROUND & AIMS: Functional interactions between the mu opioid receptor (MOR) and delta opioid receptor (DOR) represent a potential target for novel analgesics and may drive the effects of the clinically approved drug eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome. Although the enteric nervous system (ENS) is a likely site of action, the coexpression and potential interaction between MOR and DOR in the ENS are largely undefined. In the present study, we have characterized the distribution of MOR in the mouse ENS and examined MOR-DOR interactions by using pharmacologic and cell biology techniques. METHODS: MOR and DOR expression was defined by using MORmCherry and MORmCherry-DOR-eGFP knockin mice. MOR-DOR interactions were assessed by using DOR-eGFP internalization assays and by pharmacologic analysis of neurogenic contractions of the colon. RESULTS: Although MOR was expressed by approximately half of all myenteric neurons, MOR-positive submucosal neurons were rarely observed. There was extensive overlap between MOR and DOR in both excitatory and inhibitory pathways involved in the coordination of intestinal motility. MOR and DOR can functionally interact, as shown through heterologous desensitization of MOR-dependent responses by DOR agonists. Functional evidence suggests that MOR and DOR may not exist as heteromers in the ENS. Pharmacologic studies show no evidence of cooperativity between MOR and DOR. DOR internalizes independently of MOR in myenteric neurons, and MOR-evoked contractions are unaffected by the sequestration of DOR. CONCLUSIONS: Collectively, these findings demonstrate that although MOR and DOR are coexpressed in the ENS and functionally interact, they are unlikely to exist as heteromers under physiological conditions