Profil épidémiologique des urgences chirurgicales viscérales pédiatriques au Centre Hospitalier Universitaire de Libreville / Epidemiological profile of pediatric visceral surgical emergencies at the Libreville University Hospital Center

Objectif : Etudier les urgences chirurgicales viscérales pédiatriques au Centre Hospitalier Universitaire de Libreville (CHUL).Patients et méthodes : Il s'agissait d'une étude prospective transversale monocentrique descriptive réalisée au CHUL du 1er janvier 2018 au 30 juin 2019. Les patients âgés de 0 à 15 ans ayant présenté une urgence chirurgicale viscérale dans les services des urgences, chirurgie viscérale et thoracique et de réanimation néonatale et néonatalogie ont été inclus.Résultats : Cette étude portait sur 156 patients. L'âge moyen était de 6,67 ans avec une prédominance du sexe masculin (107/49). Quarante-deux patients étaient référés d'autres structures sanitaires. La symptomatologie évoluait depuis plus de 3 jours chez 42,3% patients. Des explorations à visée diagnostique étaient réalisées dans 145 cas, dont 90 échographies, 51 radiographies de l'abdomen sans préparation et 4 TDM. Le délai de prise en charge était de plus de 6 heures dans 82,1% cas. La pathologie la plus rencontrée était l'appendicite aigue (53 cas). Nous avions répertorié 9 décès dont 7 en post-opératoire. La durée moyenne d'hospitalisation était de 7 jours avec des extrêmes de 3 et 54 jours.Conclusion : Les urgences chirurgicales viscérales occupent une place de choix dans la pathologie chirurgicale en général et chez l'enfant en particulier. La mortalité concerne majoritairement les nouveau-nés porteurs de malformations congénitales.

Objective: To study pediatric visceral surgical emergencies at the Center Hospitalier Universitaire de Libreville (CHUL).Patients and methods: This was a descriptive single-center cross-sectional prospective study carried out at the CHUL from January 1, 2018 to June 30, 2019. Patients aged 0 to 15 years having presented a visceral surgical emergency in the emergency departments, surgery visceral and thoracic and neonatal resuscitation and neonatology were included. Results: This study involved 156 patients. The average age is 6.67 years with a predominance of the male sex (107/49).Forty-two patients were referred from other health facilities. Symptoms have evolved for more than 3 days in 42.3% of patients. Diagnostic scans were performed in 145 cases, including 90 ultrasounds and 51 unprepared abdominal xrays and 4 CT scans. The time to treatment was more than 6 hours in 82.1% of cases. The most common pathology was acute appendicitis (53 cases). We have identified 9 deaths, including 7 postoperative. The average length of hospital stay was 7 days with extremes of 3 and 54 days. Conclusion: Visceral surgical emergencies occupy a prominent place in surgical pathology in general and in children in particular. Mortality mainly concerns newborns with congenital malformations.

Transient receptor potential channels in sensory mechanisms of the lower urinary tract.

Disruptions to sensory pathways in the lower urinary tract commonly occur and can give rise to lower urinary tract symptoms (LUTS). The unmet clinical need for treatment of LUTS has stimulated research into the molecular mechanisms that underlie neuronal control of the bladder and transient receptor potential (TRP) channels have emerged as key regulators of the sensory processes that regulate bladder function. TRP channels function as molecular sensors in urothelial cells and afferent nerve fibres and can be considered the origin of bladder sensations. TRP channels in the lower urinary tract contribute to the generation of normal and abnormal bladder sensations through a variety of mechanisms, and have demonstrated potential as targets for the treatment of LUTS in functional disorders of the lower urinary tract.

Abnormal Neuronal Response to Rectal and Anal Stimuli in Patients Treated for Distal Rectal Cancer With High-Dose Chemoradiotherapy Followed By Watchful Waiting.

BACKGROUND: Watchful waiting in patients with rectal cancer with complete clinical response after chemoradiation therapy has gained increased popularity to avoid morbidity and mortality associated with surgery. Irradiation of the pelvis causes bowel dysfunction, but the effect on anorectal sensory function remains obscure in this patient category. OBJECTIVE: The aim of this study was to characterize the sensory pathways of the gut-brain axis in patients with rectal cancer treated solely with chemoradiation therapy (nonconventional regime/dose) compared with healthy volunteers. DESIGN: This is an explorative study. SETTINGS: Sensory evaluation by rectal distension was performed and cortical evoked potentials were recorded during rapid balloon distensions of the rectum and anal canal. Latencies and amplitudes of cortical evoked potentials were compared, and the relative amplitude of 5 spectral bands from recorded cortical evoked potentials was used as an additional proxy of neuronal processing. PATIENTS: Patients with rectal cancer solely with chemoradiation therapy (n = 13) a median of 3.2 years ago (range, 2.3-5.6 y) and healthy volunteers (n = 13) were included. MAIN OUTCOME MEASURES: Cortical evoked potentials were measured. RESULTS: Patients had 35% lower rectal capacity at a maximum tolerable volume (p = 0.007). We found no differences in rectal cortical evoked potential latencies (p = 0.09) and amplitudes (p = 0.38) between groups. However, spectral analysis of rectal cortical evoked potentials showed a decrease in θ (4-8 Hz) and an increase in ß (12-32 Hz) band activity in patients (all p < 0.001). Anal cortical potentials showed an increase in α (8-12 Hz) and ß and a decrease in γ (32-70 Hz) band activity (all p < 0.001) in patients compared with healthy volunteers. LIMITATIONS: This is an explorative study of limited size. CONCLUSIONS: Chemoradiation therapy for distal rectal cancer causes abnormal cortical processing of both anal and rectal sensory input. Such central changes may play a role in symptomatic patients, especially when refractory to local treatments. See Video Abstract at http://links.lww.com/DCR/B270. RESPUESTA NEURONAL ANORMAL A ESTÍMULOS RECTALES Y ANALES, EN PACIENTES TRATADOS POR CÁNCER RECTAL DISTAL, CON QUIMIORRADIOTERAPIA DE DOSIS ALTA, SEGUIDA DE ESPERA VIGILANTE: La espera vigilante en pacientes de cáncer rectal, con respuesta clínica completa después de la quimiorradiación, ha ganado una mayor popularidad en evitar la morbilidad y mortalidad asociadas con la cirugía. La irradiación de la pelvis causa disfunción intestinal, pero el efecto sobre la función sensorial ano-rectal sigue siendo no claro, en esta categoría de pacientes.El objetivo de este estudio, fue caracterizar las vías sensoriales del eje intestino-cerebro en pacientes con cáncer rectal, tratados únicamente con quimiorradiación (régimen / dosis no convencional), en comparación con voluntarios sanos.Es un estudio exploratorio.Se realizó una evaluación sensorial por distensión rectal y se registraron los potenciales evocados corticales, durante las distensiones rápidas con balón en recto y canal anal. Se compararon las latencias y amplitudes de los potenciales evocados corticales, y la amplitud relativa de cinco bandas espectrales registradas, de potenciales evocados corticales, se usaron como proxy adicional del procesamiento neuronal.Pacientes de cáncer rectal, únicamente con terapia de quimiorradiación (n = 13) mediana de 3.2 años (rango 2.3-5.6) y voluntarios sanos (n = 13).Potenciales evocados corticales.Pacientes tuvieron una capacidad rectal menor del 35%, al volumen máximo tolerable (p = 0.007). No encontramos diferencias en las latencias potenciales evocadas corticales rectales (p = 0.09) y amplitudes (p = 0.38) entre los grupos. Sin embargo, el análisis espectral de los potenciales evocados corticales rectales, mostró una disminución en theta (4-8 Hz) aumento en beta (12-32 Hz), y actividad en banda en pacientes (todos p <0.001). Los potenciales evocados corticales anales mostraron un aumento en alfa (8-12 Hz) y beta, disminución en gamma (32-70 Hz), y actividad en banda (todos p <0.001), en pacientes comparados a voluntarios sanos.Este es un estudio exploratorio de tamaño limitado.La quimiorradiación para el cáncer rectal distal, ocasiona procesos corticales sensoriales anormales anales y rectales. Tales cambios centrales pueden desempeñar un papel en pacientes sintomáticos, especialmente cuando son refractarios a tratamientos locales. Consulte Video Resumen en http://links.lww.com/DCR/B270.

Exaggerated potassium current reduction by oxytocin in visceral sensory neurons following chronic intermittent hypoxia.

Oxytocin (OT) from the hypothalamus is increased in several cardiorespiratory nuclei and systemically in response to a variety of stimuli and stressors, including hypoxia. Within the nucleus tractus solitarii (nTS), the first integration site for cardiorespiratory reflexes, OT enhances synaptic transmission, action potential (AP) discharge, and cardiac baroreflex gain. The hypoxic stressor obstructive sleep apnea, and its CIH animal model, elevates blood pressure and alters heart rate variability. The nTS receives sensory input from baroafferent neurons that originate in the nodose ganglia. Nodose neurons express the OT receptor (OTR) whose activation elevates intracellular calcium. However, the influence of OT on other ion channels, especially potassium channels important for neuronal activity during CIH, is less known. This study sought to determine the mechanism (s) by which OT modulates sensory afferent-nTS mediated reflexes normally and after CIH. Nodose ganglia neurons from male Sprague-Dawley rats were examined after 10d CIH (6% O2 every 3 min) or their normoxic (21% O2) control. OTR mRNA and protein were identified in Norm and CIH ganglia and was similar between groups. To examine OTR function, APs and potassium currents (IK) were recorded in dissociated neurons. Compared to Norm, after CIH OT depolarized neurons and reduced current-induced AP discharge. After CIH OT also produced a greater reduction in IK that where tetraethylammonium-sensitive. These data demonstrate after CIH OT alters ionic currents in nodose ganglia cells to likely influence cardiorespiratory reflexes and overall function.

Extensive Inhibitory Gating of Viscerosensory Signals by a Sparse Network of Somatostatin Neurons.

Integration and modulation of primary afferent sensory information begins at the first terminating sites within the CNS, where central inhibitory circuits play an integral role. Viscerosensory information is conveyed to the nucleus of the solitary tract (NTS) where it initiates neuroendocrine, behavioral, and autonomic reflex responses that ensure optimal internal organ function. This excitatory input is modulated by diverse, local inhibitory interneurons, whose functions are not clearly understood. Here we show that, in male rats, 65% of somatostatin-expressing (SST) NTS neurons also express GAD67, supporting their likely role as inhibitory interneurons. Using whole-cell recordings of NTS neurons, from horizontal brainstem slices of male and female SST-yellow fluorescent protein (YFP) and SST-channelrhodopsin 2 (ChR2)-YFP mice, we quantified the impact of SST-NTS neurons on viscerosensory processing. Light-evoked excitatory photocurrents were reliably obtained from SST-ChR2-YFP neurons (n = 16) and the stimulation-response characteristics determined. Most SST neurons (57%) received direct input from solitary tract (ST) afferents, indicating that they form part of a feedforward circuit. All recorded SST-negative NTS neurons (n = 72) received SST-ChR2 input. ChR2-evoked PSCs were largely inhibitory and, in contrast to previous reports, were mediated by both GABA and glycine. When timed to coincide, the ChR2-activated SST input suppressed ST-evoked action potentials at second-order NTS neurons, demonstrating strong modulation of primary viscerosensory input. These data indicate that the SST inhibitory network innervates broadly within the NTS, with the potential to gate viscerosensory input to powerfully alter autonomic reflex function and other behaviors.SIGNIFICANCE STATEMENT Sensory afferent input is modulated according to state. For example the baroreflex is altered during a stress response or exercise, but the basic mechanisms underpinning this sensory modulation are not fully understood in any sensory system. Here we demonstrate that the neuronal processing of viscerosensory information begins with synaptic gating at the first central synapse with second-order neurons in the NTS. These data reveal that the somatostatin subclass of inhibitory interneurons are driven by visceral sensory input to play a major role in gating viscerosensory signals, placing them within a feedforward circuit within the NTS.

Multiple Pulmonary and Hepatic Arteriovenous Malformations in a Patient With Rendu-Osler-Weber Disease / Malformaciones arteriovenosas pulmonares y hepáticas múltiples en un paciente con enfermedad de Rendu-Osler-Webe

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Visceral-afferent signals from the cardiovascular system, but not urinary urge, affect startle eye blink.

The aim of the current study was to investigate if startle methodology is suitable to reflect urinary urgency. Eighteen healthy men were tested on two separate days, each including an ingestion of fluid until 80% of the subjective urge to micturate was reached. EMG responses to acoustic startle stimuli were assessed before and after micturition, as well as in the early and late cardiac cycle phases (230 vs. 530 ms after a cardiac R-wave). Sonographic assessment confirmed bladder-filling status. Emotional arousal, stress, urge and unpleasantness ratings, as well as mean blood pressure were higher before than after micturition. Startle eye blink responses were lower during the early than during the late cardiac cycle phase, but were not affected by bladder filling status. We conclude that startle methodology is suitable for the investigation of afferent signals from the cardiovascular system, but not to reflect urinary urgency. This result may be due to different neurophysiological mechanisms underlying afferent signals from the bladder compared to other visceral organs or interference with affective states or sympathetic activation associated with bladder filling. Notwithstanding, the present research protocol of fluid intake, sonographic assessment of the bladder, and subjective reports, can be applied to examine effects of urinary urge on physiological and psychological processes.

Six-Month Results of Selective Bladder Denervation in Women with Refractory Overactive Bladder.

PURPOSE: We report 6-month efficacy and safety outcomes of selective bladder denervation in women with refractory overactive bladder. MATERIALS AND METHODS: Women with refractory overactive bladder and urgency urinary incontinence were enrolled in 2 prospective feasibility studies with the same entry criteria. They underwent selective bladder denervation of the subtrigonal region containing afferent sensory nerves. Patients were followed for 6 months and assessed for adverse events, overactive bladder symptoms and health related quality of life measures. RESULTS: In the 35 women with a mean age of 66 years who were enrolled in the study all selective bladder denervation procedures were completed successfully. During 6 months of followup the symptom improvement based on 3-day bladder diaries was 59% for urgency urinary incontinence (p <0.001), 59% for urinary incontinence (p <0.001), 39% for urgency (p <0.001), 9% for urinary frequency (p = 0.01) and 27% for the total urgency and frequency score (p <0.001). Most of this treatment benefit was realized in the first month. The rate of clinical success, defined as a 50% or greater reduction in urgency urinary incontinence, was 70%, treatment benefit was reported in 75% of patients and the dry/cure rate was 27%. Statistically significant improvements during 6 months were identified on the symptom bother and health related quality of life scales on the OAB-q (Overactive Bladder Questionnaire) and on all KHQ (King's Health Questionnaire) domains except general health perception. Device or procedure related adverse events were reported in 6 patients (17%). CONCLUSIONS: Pooled results of 2 prospective feasibility studies suggest that selective bladder denervation is a promising minimally invasive treatment option in women with refractory overactive bladder.

Sensory Function and Chronic Pain in Multiple Sclerosis.

Objective: To examine whether hypoesthesia and chronic pain are related in patients with MS. Methods: Sixty-seven MS patients with pain and 80 persons without MS were included. Sensory functioning was tested by bedside neurological examination. Touch, joint position (dorsal column-medial lemniscus pathway), temperature sense, and pain (spinothalamic tract) were tested. Pain intensity was measured by the Colored Analogue Scale (CAS Intensity) and the Faces Pain Scale (FPS); pain affect was also measured by CAS Affect and Number of Words Chosen-Affective (NWC-A). Mood was assessed with the SCL-90 anxiety and depression subscales and the Beck Depression Inventory (BDI). Results: A significant negative relationship was found between pain intensity and the function of the dorsal column-medial lemniscal pathway, but not with the spinothalamic tract. Conclusion: In addition to the already known relation between hyperesthesia and pain, hypoesthesia for touch and joint position also seems to be related to chronic pain in MS patients.

Anti-TNFα therapy in IBD alters brain activity reflecting visceral sensory function and cognitive-affective biases.

BACKGROUND: In inflammatory bowel disease (IBD), immune activation with increased circulating TNF-α is linked to the intensity of gastrointestinal symptoms and depression or anxiety. A central feature of depression is cognitive biases linked to negative attributions about self, the world and the future. We aimed to assess the effects of anti-TNFα therapy on the central processing of self-attribution biases and visceral afferent information in patients with Crohn's disease. METHODS: We examined 9 patients with Crohn's disease (age 26.1±10.6. yrs, 5 female, 5 ileocolonic, 2 colonic and 2 ileal disease) during chronic anti-TNFα therapy (5 adalimumab, 4 infliximab). Patients were studied twice in randomized order before and after anti-TNFα administration. On each occasion patients underwent functional magnetic resonance imaging (fMRI) of the brain during a test of implicit attribution biases regarding sickness/health and undertook a standardized nutrient challenge. RESULTS: Following anti-TNFα treatment, ratings of 'fullness' following nutrient challenge reduced compared to pre-treatment ratings (p<0.05). Reaction times revealed improved processing of self-related and positive health words, consistent with improved implicit sense of wellbeing that correlated with improvements in sensory function after treatment (r = 0.67, p<0.05). Treatment-associated improvements in implicit processing were mirrored by alterations of prefrontal, amygdala, posterior cingulate and visual regions. Between patients, the degree of functional amygdala change was additionally explained by individual differences in attention regulation and body awareness rankings. CONCLUSION: In patients with Crohn's disease, anti-TNFα administration reduces visceral sensitivity and improves implicit cognitive-affective biases linked to alterations in limbic (amygdala) function.

Structure and development of the subesophageal zone of the Drosophila brain. II. Sensory compartments.

The subesophageal zone (SEZ) of the Drosophila brain processes mechanosensory and gustatory sensory input from sensilla located on the head, mouth cavity and trunk. Motor output from the SEZ directly controls the movements involved in feeding behavior. In an accompanying paper (Hartenstein et al., ), we analyzed the systems of fiber tracts and secondary lineages to establish reliable criteria for defining boundaries between the four neuromeres of the SEZ, as well as discrete longitudinal neuropil domains within each SEZ neuromere. Here we use this anatomical framework to systematically map the sensory projections entering the SEZ throughout development. Our findings show continuity between larval and adult sensory neuropils. Gustatory axons from internal and external taste sensilla of the larva and adult form two closely related sensory projections, (a) the anterior central sensory center located deep in the ventromedial neuropil of the tritocerebrum and mandibular neuromere, and (b) the anterior ventral sensory center (AVSC), occupying a superficial layer within the ventromedial tritocerebrum. Additional, presumed mechanosensory terminal axons entering via the labial nerve define the ventromedial sensory center (VMSC) in the maxilla and labium. Mechanosensory afferents of the massive array of chordotonal organs (Johnston's organ) of the adult antenna project into the centrolateral neuropil column of the anterior SEZ, creating the antenno-mechanosensory and motor center (AMMC). Dendritic projections of dye back-filled motor neurons extend throughout a ventral layer of the SEZ, overlapping widely with the AVSC and VMSC. Our findings elucidate fundamental structural aspects of the developing sensory systems in Drosophila.

Pharyngolaryngeal Sensory Deficits in Patients with Middle Cerebral Artery Infarction: Lateralization and Relation to Overall Dysphagia Severity.

BACKGROUND: Dysphagia is a frequent and dangerous complication of acute stroke. Apart from a well-timed oropharyngeal muscular contraction pattern, sensory feedback is of utmost importance for safe and efficient swallowing. In the present study, we therefore analyzed the relation between pharyngolaryngeal sensory deficits and post-stroke dysphagia (PSD) severity in a cohort of acute stroke patients with middle cerebral artery (MCA) infarction. METHODS: Eighty-four first-ever MCA stroke patients (41 left, 43 right) were included in this trial. In all patients, fiberoptic endoscopic evaluation of swallowing (FEES) was performed according to a standardized protocol within 96 h after stroke onset. PSD was classified according to the 6-point fiberoptic endoscopic dysphagia severity scale. Pharyngolaryngeal sensation was semi-quantitatively evaluated by a FEES-based touch technique. RESULTS: PSD severity was closely related to the pharyngolaryngeal sensory deficit. With regards to lateralization of the sensory deficit, there was a slight but significant preponderance of sensory loss contralateral to the side of stroke. Apart from that, right hemispheric stroke patients were found to present with a more severe PSD. CONCLUSIONS: This study provides evidence that an intact sensory feedback is of utmost importance to perform nonimpaired swallowing and highlights the key role of disturbed pharyngeal and laryngeal afferents in the pathophysiology of PSD.

Getting to the heart of the matter: Does aberrant interoceptive processing contribute towards emotional eating?

According to estimates from Public Health England, by 2034 70% of adults are expected to be overweight or obese, therefore understanding the underpinning aetiology is a priority. Eating in response to negative affect contributes towards obesity, however, little is known about the underlying mechanisms. Evidence that visceral afferent signals contribute towards the experience of emotion is accumulating rapidly, with the emergence of new influential models of 'active inference'. No longer viewed as a 'bottom up' process, new interoceptive facets based on 'top down' predictions have been proposed, although at present it is unclear which aspects of interoception contribute to aberrant eating behaviour and obesity. Study one examined the link between eating behaviour, body mass index and the novel interoceptive indices; interoceptive metacognitive awareness (IAw) and interoceptive prediction error (IPE), as well as the traditional measures; interoceptive accuracy (IAc) and interoceptive sensibility (IS). The dissociation between these interoceptive indices was confirmed. Emotional eaters were characterised by a heightened interoceptive signal but reduced meta-cognitive awareness of their interoceptive abilities. In addition, emotional eating correlated with IPE; effects that could not be accounted for by differences in anxiety and depression. Study two confirmed the positive association between interoceptive accuracy and emotional eating using a novel unbiased heartbeat discrimination task based on the method of constant stimuli. Results reveal new and important mechanistic insights into the processes that may underlie problematic affect regulation in overweight populations.

From psychological moments to mortality: A multidisciplinary synthesis on heart rate variability spanning the continuum of time.

Heart rate variability (HRV) indexes functioning of the vagus nerve, arguably the most important nerve in the human body. The Neurovisceral Integration Model has provided a structural framework for understanding brain-body integration, highlighting the role of the vagus in adaptation to the environment. In the present paper, we emphasise a temporal framework in which HRV may be considered a missing, structural link between psychological moments and mortality, a proposal we label as Neurovisceral Integration Across a Continuum of Time (or NIACT). This new framework places neurovisceral integration on a dimension of time, highlighting implications for lifespan development and healthy aging, and helping to bridge the gap between clearly demarcated disciplines such as psychology and epidemiology. The NIACT provides a novel framework, which conceptualizes how everyday psychological moments both affect and are affected by the vagus in ways that have long-term effects on mortality risk. We further emphasize that a longitudinal approach to understanding change in vagal function over time may yield novel scientific insights and important public health outcomes.

Dynasore blocks evoked release while augmenting spontaneous synaptic transmission from primary visceral afferents.

The recycling of vesicle membrane fused during exocytosis is essential to maintaining neurotransmission. The GTPase dynamin is involved in pinching off membrane to complete endocytosis and can be inhibited by dynasore resulting in activity-dependent depletion of release-competent synaptic vesicles. In rat brainstem slices, we examined the effects of dynasore on three different modes of glutamate release-spontaneous, evoked, and asynchronous release-at solitary tract (ST) inputs to neurons in the nucleus of the solitary tract (NTS). Intermittent bursts of stimuli to the ST interspersed with pauses in stimulation allowed examination of these three modes in each neuron continuously. Application of 100 µM dynasore rapidly increased the spontaneous EPSC (sEPSC) frequency which was followed by inhibition of both ST-evoked EPSCs (ST-EPSC) as well as asynchronous EPSCs. The onset of ST-EPSC failures was not accompanied by amplitude reduction-a pattern more consistent with conduction block than reduced probability of vesicle release. Neither result suggested that dynasore interrupted endocytosis. The dynasore response profile resembled intense presynaptic TRPV1 activation. The TRPV1 antagonist capsazepine failed to prevent dynasore increases in sEPSC frequency but did prevent the block of the ST-EPSC. In contrast, the TRPV1 antagonist JNJ 17203212 prevented both actions of dynasore in neurons with TRPV1-expressing ST inputs. In a neuron lacking TRPV1-expressing ST inputs, however, dynasore promptly increased sEPSC rate followed by block of ST-evoked EPSCs. Together our results suggest that dynasore actions on ST-NTS transmission are TRPV1-independent and changes in glutamatergic transmission are not consistent with changes in vesicle recycling and endocytosis.

Gastric distension causes changes in heart rate and arterial blood pressure by affecting the crosstalk between vagal and splanchnic systems in anesthetised rats.

Various hindbrain nuclei have been demonstrated to be involved in the control of the cardiovascular reflexes elicited by both non-noxious and noxious gastric distension, through parasympathetic and sympathetic activation. The different role played by the branches of autonomic nervous system in exerting these effects and their crosstalk in relation to low-/high-pressure distension rate has not been examined yet. Therefore, in the present work, monolateral and bilateral vagotomy and splanchnicotomy were performed in anesthetised rats to analyse the involvement of hindbrain nuclei in haemodynamic changes caused by gastric distension at high (80 mmHg) and low (15 mmHg) pressure. The analysis of c-Fos expression in neuronal areas involved in cardiovascular control allowed us to examine their recruitment in response to various patterns of gastric distension and the crosstalk between vagal and splanchnic systems. The results obtained show that the low-pressure (non-noxious) gastric distension increases both heart rate and arterial blood pressure. In addition, the vagus nerve and hindbrain nuclei, such as nucleus ambiguous, ventrolateral medulla and lateral reticular nucleus, appear to be primarily involved in observed responses. In particular, we have found that although vagus nerve plays a central role in exerting those cardiovascular reflex changes at low gastric distension, for its functional expression an intact splanchnic system is mandatory. Hence, the absence of splanchnic input attenuates pressor responses or turns them into depressor responses. Instead at high-pressure (noxious) gastric distension, the splanchnic nerve represents the primary component in regulating the reflex cardiovascular effects.

Effects of methylmercury on spinal cord afferents and efferents-A review.

Methylmercury (MeHg) is an environmental neurotoxicant of public health concern. It readily accumulates in exposed humans, primarily in neuronal tissue. Exposure to MeHg, either acutely or chronically, causes severe neuronal dysfunction in the central nervous system and spinal neurons; dysfunction of susceptible neuronal populations results in neurodegeneration, at least in part through Ca2+-mediated pathways. Biochemical and morphologic changes in peripheral neurons precede those in central brain regions, despite the fact that MeHg readily crosses the blood-brain barrier. Consequently, it is suggested that unique characteristics of spinal cord afferents and efferents could heighten their susceptibility to MeHg toxicity. Transient receptor potential (TRP) ion channels are a class of Ca2+-permeable cation channels that are highly expressed in spinal afferents, among other sensory and visceral organs. These channels can be activated in numerous ways, including directly via chemical irritants or indirectly via Ca2+ release from intracellular storage organelles. Early studies demonstrated that MeHg interacts with heterologous TRP channels, though definitive mechanisms of MeHg toxicity on sensory neurons may involve more complex interaction with, and among, differentially-expressed TRP populations. In spinal efferents, glutamate receptors of the N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and possibly kainic acid (KA) classes are thought to play a major role in MeHg-induced neurotoxicity. Specifically, the Ca2+-permeable AMPA receptors, which are abundant in motor neurons, have been identified as being involved in MeHg-induced neurotoxicity. In this review, we will describe the mechanisms that could contribute to MeHg-induced spinal cord afferent and efferent neuronal degeneration, including the possible mediators, such as uniquely expressed Ca2+-permeable ion channels.

Extracellular adenosine 5'-triphosphate concentrations changes in rat spinal cord associated with the activation of urinary bladder afferents. A microdialysis study. / Variação da concentração extracelular de 5'-trifosfato de adenosina na medula espinal de rata associadas a fibras aferentes vesicais. Um estudo com microdiálise

ABSTRACT Objective To determine adenosine 5’-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. Methods A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5’-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Results Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5’-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5’-triphosphate levels and no further increase in adenosine 5’-triphosphate was observed during bladder distension. Conclusion Adenosine 5’-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5’-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5’-triphosphate itself.

RESUMO Objetivo Determinar as concentrações extracelulares do 5’-trifosfato de adenosina no interstício dos segmentos medulares L6-S1, em condições basais ou durante a ativação mecânica e química das fibras aferentes vesicais. Métodos Um cateter de microdiálise foi implantado no sentido transversal na parte dorsal da medula espinal, entre os segmentos L6-S1 de ratas. O microdialisado foi coletado em intervalos de 15 minutos, durante 135 minutos, com os animais anestesiados. A concentração de 5’-trifosfato de adenosina nas amostras foi determinada mediante ensaio de bioluminescência. Em um grupo de animais (n=7), as amostras de microdialisado foram obtidas com a bexiga vazia, com distensão da bexiga para volume de 20 ou 40cmH2O, com solução salina, solução salina com ácido acético, ou solução salina com capsaicina. Em outro grupo (n=6), foi realizada com a bexiga distendida, e a solução para microdiálise continha o inibidor de ectonucleotidase ARL 67156. Resultados Os níveis extracelulares de trifosfato de adenosina no início do estudo foram 110,9±35,36fmol/15 minutos (média±EPM, n=13), e a distensão da bexiga causou um aumento nos níveis de 5’-trifosfato de adenosina, o que não foi observado após a distensão da bexiga com solução salina contendo capsaicina (10µM). A microdiálise com solução contendo ARL 67156 (1mM) foi associada com significante aumento dos níveis de trifosfato de adenosina extracelular, e nenhum aumento do trifosfato de adenosina foi observado durante a distensão da bexiga. Conclusão O 5’-trifosfato de adenosina está presente no interstício do segmento L6-S1 da medula espinal, é degradado por ectonucleotidases, e sua concentração aumentou com a ativação das fibras aferentes mecanossensíveis da bexiga, mas não das quimiossensíveis. O 5’-trifosfato de adenosina pode ter sido liberado das terminações centrais dos neurônios aferentes primários mecanossensíveis ou, mais provavelmente, de neurônios espinais intrínsecos, ou ainda de células gliais. Sua liberação parece ser modulada por fibras aferentes primárias da bexiga ativadas pela capsaicina ou pelo próprio 5’-trifosfato de adenosina.

Spinal afferent nerve endings in visceral organs: recent advances.

Spinal afferent neurons play a major role in detection and transduction of painful stimuli from internal (visceral) organs. Recent technical advances have made it possible to visualize the endings of spinal afferent axons in visceral organs. Although it is well known that the sensory nerve cell bodies of spinal afferents reside within dorsal root ganglia (DRG), identifying their endings in internal organs has been especially challenging because of a lack of techniques to distinguish them from endings of other extrinsic and intrinsic neurons (sympathetic, parasympathetic, and enteric). We recently developed a surgical approach in live mice that allows selective labeling of spinal afferent axons and their endings, revealing a diverse array of different types of varicose and nonvaricose terminals in visceral organs, particularly the large intestine. In total, 13 different morphological types of endings were distinguished in the mouse distal large intestine, originating from lumbosacral DRG. Interestingly, the stomach, esophagus, bladder, and uterus had less diversity in their types of spinal afferent endings. Taken together, spinal afferent endings (at least in the large intestine) appear to display greater morphological diversity than vagal afferent endings that have previously been extensively studied. We discuss some of the new insights that these findings provide.