scholarly journals A130 RETROGRADE TRACING ANALYSIS OF THE SENSORY INNERVATION OF THE MOUSE COLON

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 150-151
Author(s):  
S Osman ◽  
A E Lomax
Keyword(s):  
Visceral Pain ◽  
Receptive Fields ◽  
Fluorescence Emission ◽  
Distal Colon ◽  
Proximal Colon ◽  
Sensory Innervation ◽  
Afferent Neurons ◽  
Drg Neurons ◽  
Fluorescence Emission Spectra ◽  
Fast Blue

Abstract Background Visceral pain is a primary symptom of many gastrointestinal diseases. One feature of visceral pain is its vague localization. We hypothesized that overlap in the receptive fields of spinal primary afferent neurons that innervate the gut may contribute to this vague localization. Many studies have confirmed that the proximal and distal colon are mainly innervated by spinal afferent neurons with cell bodies in thoraco-lumbar and lumbo-sacral dorsal root ganglia (DRG), respectively. However, no murine studies have examined whether individual DRG neurons simultaneously innervate both proximal and distal colon. Aims To determine the extent of overlap in receptive fields of colon-projecting DRG neurons. Methods C57BL/6 mice (n=8) were anesthetized, and two retrograde neuronal tracers with distinct fluorescence emission spectra (Fast blue and DiI) were injected separately into the smooth muscle layers of proximal and distal colon. Mice were left for 10–13 days for dye transport, before being euthanized. Thoraco, lumbar and lumbo-sacral DRGs (T8-13, L1-4, L5-S2) were dissected and fixed in 4% paraformaldehyde overnight. 12μm cryostat sections were obtained and analyzed using a fluorescent microscope equipped with filter cubes that detect Fast blue and DiI. Results When DiI was injected into the proximal colon, we observed labelling to be highest in T8-13 DRG with 12.6 +/- 4.5% of cell bodies labelled, followed by L1-4 was (8.2 +/- 1.4%) and in L5-S2 (6.5 +/- 0.8%). DiI injections into the distal colon resulted in labelling of similar numbers of neurons labelled in T8-13 and L1-4 ganglia, whereas half as many neurons were labelled in L5-S2 ganglia. This data shows that the majority of spinal afferent innervation of the colon originates in thoracolumbar DRG. Most importantly, 26.4% and 17.6% of thoracolumbar and lumbo-sacral DRG neurons labelled by Fast blue injection into the proximal colon were also double-labelled by DiI injected into the distal colon. Similarly, 16.6% and 13.8% of neurons in thoracolumbar and lumbosacral DRG labelled by Fast blue injection into the distal colon were double-labelled by DiI injected into the proximal colon. Conclusions These data reveal a surprisingly large number of DRG neurons that innervate the colon have receptive fields that cover both the proximal and distal colon, which may contribute to the poor spatial localization of pain emanating from the colon. Funding Agencies CCC, CIHR

scholarly journals A126 RETROGRADE LABELLING OF NODOSE GANGLIA IN VIVO BY FLUORESCENT TRACERS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 146-147
Author(s):  
A A Tashtush ◽  
A E Lomax
Keyword(s):  
Vagus Nerve ◽  
Principal Component ◽  
Distal Colon ◽  
Proximal Colon ◽  
Vagal Afferents ◽  
Sensory Innervation ◽  
Lower Percentage ◽  
Retrograde Labelling ◽  
Nodose Ganglia

Abstract Background The gut-brain axis is a bidirectional connection between the gastrointestinal tract (GI)and the central nervous system. The vagus nerve has been recognized as a principal component of this axis. Vagus nerve plays important role in maintaining homeostasis and normal GI functions, its afferent fibers can detect microbiota metabolites also. Many studies have demonstrated that the upper GI tract receives dense vagal innervation, which decreases distally throughout the tract. However, the distal colon sensory innervation of the vagus nerve remains controversial. Aims To illuminate the extent to which the vagus nerve innervates the colon, to determine whether anatomical evidence exists for double-labeled vagal afferents supplying the proximal and distal colon in the nodose ganglia. Methods C57Bl/6 mice (n=8) were injected in the proximal and distal colon with alternating solutions of retrograde tracers 1.7% Fast blue (FB) and 5% of lipophilic tracer DiI. Animals were left to recover for 10–13 days then underwent cardiac perfusion. Nodose ganglia were collected and fixed in 4% paraformaldehyde. 12 um tissue sections were then analyzed under a fluorescent microscope at 350nm and 555nm wavelength. Results In total, 27% of nodose cell bodies were labeled from the entire colon. Following proximal DiI injections, the percentage of labeled cell bodies in the nodose ganglia were 24.3± 3.9%. However, we observed a lower percentage of labeled neurons from the distal colon, with 9.3± 1.4% after DiI injections. FB labelling from the distal colon was three times less than that observed for DiI. Within the nodose ganglia, 40% of all distally labelled neurons were labelled with both tracers. Conclusions These findings indicate that in mice, both distal and proximal colon receives visceral sensory innervation from the vagus nerve. Thus, providing evidence for a sensory anatomical connection of the vagus nerve between these two parts of the colon. Funding Agencies CCC, CIHR

scholarly journals Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity

2016 ◽  
Vol 310 (10) ◽  
pp. G790-G798 ◽  
Author(s):  
Bin Feng ◽  
Sonali C. Joyce ◽  
G. F. Gebhart
Keyword(s):  
De Novo ◽  
Visceral Pain ◽  
Ex Vivo ◽  
Significant Proportion ◽  
Receptive Fields ◽  
Critical Factor ◽  
Sensory Innervation ◽  
Hypertonic Solution ◽  
Mechanical Stimuli ◽  
Generator Potential

The sensory innervation of the distal colorectum includes mechanically insensitive afferents (MIAs; ∼25%), which acquire mechanosensitivity in persistent visceral hypersensitivity and thus generate de novo input to the central nervous system. We utilized an optogenetic approach to bypass the process of transduction (generator potential) and focus on transformation (spike initiation) at colorectal MIA sensory terminals, which is otherwise not possible in typical functional studies. From channelrhodopsin2-expressing mice (driven by Advillin-Cre), the distal colorectum with attached pelvic nerve was harvested for ex vivo single-fiber recordings. Afferent receptive fields (RFs) were identified by electrical stimulation and tested for response to mechanical stimuli (probing, stroking, and stretch), and afferents were classified as either MIAs or mechanosensitive afferents (MSAs). All MIA and MSA RFs were subsequently stimulated optically and MIAs were also tested for activation/sensitization with inflammatory soup (IS), acidic hypertonic solution (AHS), and/or bile salts (BS). Responses to pulsed optical stimuli (1–10 Hz) were comparable between MSAs and MIAs whereas 43% of MIAs compared with 86% of MSAs responded tonically to stepped optical stimuli. Tonic-spiking MIAs responded preferentially to AHS (an osmotic stimulus) whereas non-tonic-spiking MIAs responded to IS (an inflammatory stimulus). A significant proportion of MIAs were also sensitized by BS. These results reveal transformation as a critical factor underlying the differences between MIAs (osmosensors vs. inflammatory sensors), revealing a previously unappreciated heterogeneity of MIA endings. The current study draws attention to the sensory encoding of MIA nerve endings that likely contribute to afferent sensitization and thus have important roles in visceral pain.

Mechanical Response Properties of A and C Primary Afferent Neurons Innervating the Rat Intracranial Dura

2002 ◽  
Vol 88 (6) ◽  
pp. 3021-3031 ◽  
Author(s):  
Dan Levy ◽  
Andrew M. Strassman
Keyword(s):  
Trigeminal Ganglion ◽  
Mechanical Response ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Sensory Innervation ◽  
Afferent Neurons ◽  
Rapid Adaptation ◽  
Response Curves ◽  
Response Properties ◽  
Stimulus Response

The intracranial dura receives a small-fiber sensory innervation from the trigeminal ganglion that is thought to be involved in some types of headaches, including migraine. Mechanical response properties of dural afferent neurons were examined to investigate variation across the population in the properties of threshold, slope, adaptation, and incidence of mechanosensitivity. Dural afferent neurons were recorded in the trigeminal ganglion of urethan-anesthetized rats and were identified by their constant-latency response to dural shock. Neurons were classified as fast A (>5 m/s), slow A (5 ≥ conduction velocity (CV) ≥ 1.5 m/s), or C (<1.5 m/s), based on response latency to dural shock. Mechanical receptive fields were identified by stroking or indenting the outer surface of the dura. Stimulus-response curves were obtained from responses to 2-s constant-force indenting stimuli of graded intensities delivered to the dural receptive field with a servo force-controlled mechanical stimulator. The slow A population had the highest percentage of mechanosensitive units (97%) as well as the highest slopes and the lowest thresholds. Thus by all three criteria, the slow As had the highest mechanosensitivity. Conversely, the fast A population had the lowest mechanosensitivity in that it had the lowest percentage of mechanosensitive units (66%), the lowest slopes, and the highest thresholds. The C population was intermediate with respect to all three properties but was much more similar to the slow As than to the fast As. All three fiber classes showed a negative correlation between slope and threshold. The majority of neurons showed a slowly adapting response to a maintained 2-s stimulus. Adapting neurons could be subdivided based on whether the fitted exponential curve decayed to zero or to a nonzero plateau; the latter group contained the most sensitive neurons in that they had the lowest thresholds and highest slopes. Nonadapting neurons generally had lower initial firing rates than adapting neurons. Fast A neurons exhibited greater and more rapid adaptation than slow A and C neurons. Neurons with the lowest slopes, regardless of CV, had relatively rapid adaptation. The more slowly conducting portion of the C population was distinguished from the other C neurons by a number of properties: more mechanically insensitive neurons, higher thresholds, and more nonadapting neurons. These differences in mechanical response properties may be related in part to differences in membrane currents involved in impulse generation that have been described in subpopulations of dorsal root ganglion cells.

scholarly journals Tetrodotoxin: A New Strategy to Treat Visceral Pain?

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 496
Author(s):  
Ana Campos-Ríos ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Paula Rivas-Ramírez ◽  
José Antonio Lamas
Keyword(s):  
Action Potentials ◽  
Channel Blocker ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Afferent Neurons ◽  
Sodium Channel Blocker ◽  
Voltage Gated Sodium Channels ◽  
New Strategy ◽  
Specific Receptors

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.

scholarly journals The Relationship between Inflammation Markers (CRP, IL-6, sCD40L) and Colorectal Cancer Stage, Grade, Size and Location

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1382
Author(s):  
Olga Martyna Koper-Lenkiewicz ◽  
Violetta Dymicka-Piekarska ◽  
Anna Justyna Milewska ◽  
Justyna Zińczuk ◽  
Joanna Kamińska
Keyword(s):  
Colorectal Cancer ◽  
Linear Regression ◽  
Tumor Size ◽  
Distal Colon ◽  
Proximal Colon ◽  
Model Parameters ◽  
Grade Group ◽  
Who Grade ◽  
The Mean ◽  
Mean Concentration

The aim of the study was the evaluation whether in primary colorectal cancer (CRC) patients (n = 55): age, sex, TNM classification results, WHO grade, tumor location (proximal colon, distal colon, rectum), tumor size, platelet count (PLT), mean platelet volume (MPV), mean platelet component (MCP), levels of carcinoembryonic antigen (CEA), cancer antigen (CA 19-9), as well as soluble lectin adhesion molecules (L-, E-, and P-selectins) may influence circulating inflammatory biomarkers: IL-6, CRP, and sCD40L. We found that CRP concentration evaluation in routine clinical practice may have an advantage as a prognostic biomarker in CRC patients, as this protein the most comprehensively reflects clinicopathological features of the tumor. Univariate linear regression analysis revealed that in CRC patients: (1) with an increase in PLT by 10 × 103/μL, the mean concentration of CRP increases by 3.4%; (2) with an increase in CA 19-9 of 1 U/mL, the mean concentration of CRP increases by 0.7%; (3) with the WHO 2 grade, the mean CRP concentration increases 3.631 times relative to the WHO 1 grade group; (4) with the WHO 3 grade, the mean CRP concentration increases by 4.916 times relative to the WHO 1 grade group; (5) with metastases (T1-4N+M+) the mean CRP concentration increases 4.183 times compared to non-metastatic patients (T1-4N0M0); (6) with a tumor located in the proximal colon, the mean concentration of CRP increases 2.175 times compared to a tumor located in the distal colon; (7) in patients with tumor size > 3 cm, the CRP concentration is about 2 times higher than in patients with tumor size ≤ 3 cm. In the multivariate linear regression model, the variables that influence the mean CRP value in CRC patients included: WHO grade and tumor localization. R2 for the created model equals 0.50, which indicates that this model explains 50% of the variance in the dependent variable. In CRC subjects: (1) with the WHO 2 grade, the mean CRP concentration rises 3.924 times relative to the WHO 1 grade; (2) with the WHO 3 grade, the mean CRP concentration increases 4.721 times in relation to the WHO 1 grade; (3) with a tumor located in the rectum, the mean CRP concentration rises 2.139 times compared to a tumor located in the distal colon; (4) with a tumor located in the proximal colon, the mean concentration of CRP increases 1.998 times compared to the tumor located in the distal colon; if other model parameters are fixed.

scholarly journals Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322545
Author(s):  
Han-Mo Chiu ◽  
Grace Hsiao-Hsuan Jen ◽  
Ying-Wei Wang ◽  
Jean Ching-Yuan Fann ◽  
Chen-Yang Hsu ◽  
...  
Keyword(s):  
Large Scale ◽  
Distal Colon ◽  
Population Based ◽  
Proximal Colon ◽  
Advanced Stage ◽  
Site Specific ◽  
Faecal Immunochemical Test ◽  
Immunochemical Test ◽  
Selection Factors

ObjectiveTo measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening.DesignA prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features.ResultsFIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80).ConclusionA large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.

Optical Properties and Zinc Nitride Thin Films Prepared Using Magnetron Reactive Sputtering

2014 ◽  
Vol 940 ◽  
pp. 11-15
Author(s):  
Jun Qin Feng ◽  
Jun Fang Chen
Keyword(s):  
Thin Films ◽  
Band Gap ◽  
Near Infrared ◽  
Fluorescence Emission ◽  
Emission Spectra ◽  
Sem Images ◽  
Fluorescence Emission Spectra ◽  
Glass Substrates ◽  
Zinc Nitride ◽  
Direct Band

Zinc nitride films were deposited by ion sources-assisted magnetron sputtering with the use of Zn target (99.99% purity) on 7059 glass substrates. The films were characterized by XRD, SEM and EDS, the results of which show that the polycrystalline zinc nitride thin film can be grown on the glass substrates, the EDS spectrum confirmed the chemical composition of the films and the SEM images revealed that the zinc nitride thin films have a dense structure. Ultraviolet-visible-near infrared spectrophotometer was used to study the transmittance behaviors of zinc nitride thin films, which calculated the optical band gap by Davis Mott model. The results of the fluorescence emission spectra show the zinc nitride would be a direct band gap semiconductor material.

scholarly journals Long range synchronization within the enteric nervous system underlies propulsion along the large intestine in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nick J. Spencer ◽  
Lee Travis ◽  
Lukasz Wiklendt ◽  
Marcello Costa ◽  
Timothy J. Hibberd ◽  
...  
Keyword(s):  
Nervous System ◽  
Smooth Muscle ◽  
Enteric Nervous System ◽  
Lymphatic Vessels ◽  
Distal Colon ◽  
Distal Region ◽  
Proximal Colon ◽  
Synchronous Firing ◽  
Electrophysiological Recordings ◽  
Intrinsic Neurons

AbstractHow the Enteric Nervous System (ENS) coordinates propulsion of content along the gastrointestinal (GI)-tract has been a major unresolved issue. We reveal a mechanism that explains how ENS activity underlies propulsion of content along the colon. We used a recently developed high-resolution video imaging approach with concurrent electrophysiological recordings from smooth muscle, during fluid propulsion. Recordings showed pulsatile firing of excitatory and inhibitory neuromuscular inputs not only in proximal colon, but also distal colon, long before the propagating contraction invades the distal region. During propulsion, wavelet analysis revealed increased coherence at ~2 Hz over large distances between the proximal and distal regions. Therefore, during propulsion, synchronous firing of descending inhibitory nerve pathways over long ranges aborally acts to suppress smooth muscle from contracting, counteracting the excitatory nerve pathways over this same region of colon. This delays muscle contraction downstream, ahead of the advancing contraction. The mechanism identified is more complex than expected and vastly different from fluid propulsion along other hollow smooth muscle organs; like lymphatic vessels, portal vein, or ureters, that evolved without intrinsic neurons.

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