Visceral Responses Research Articles

Does Acute Heat Stress Differentially‐Modulate RVLM Gene Expression of Ionotropic Neurotransmitter Receptors in Young and Aged F344 Rats?

The rostral ventrolateral medulla (RVLM) is involved in the regulation of sympathetic nerve discharge (SND) and arterial blood pressure. Acute hyperthermia produces marked activation of visceral SND in young rats, and the functional integrity of this brainstem region is crucial for sustaining visceral sympathoexcitation to increased internal body temperature (Tc). Visceral SND responses to increased Tc are attenuated in aged compared with young F344 rats, and central mechanisms contributing to age‐associated alterations in SND responses to hyperthermia are not well‐established. The balance between excitatory and inhibitory inputs, mediated primarily by glutamate and GABA neural systems, is important for regulating RVLM neuronal activity. In the present study we hypothesized that, in response to acute hyperthermia, the RVLM gene expression of various excitatory and inhibitory ionotropic neurotransmitter receptors would demonstrate age‐related differences. Tc was increased from 38°C to 41.5°C in young (3–4 months) and aged (23–24 months) anesthetized F344 rats. Total RNA was extracted from RVLM‐containing micropunches and gene expression analysis for ionotropic neurotransmitter receptor subunits was performed using TaqMan real time RT‐PCR. Gene expression levels of glutamate, GABA and glycine neurotransmitter binding receptor subunits were compared between age groups. Gene expression analysis revealed an upregulation in some, but not all, major excitatory NMDA and AMPA neurotransmitter receptor subunits in young compared with aged rats. In addition, major subunits of the inhibitory GABA and glycine receptors demonstrated substantial upregulation in aged compared with young rats. These preliminary data suggest that, in response to acute hyperthermia, aging modulates the functional balance of RVLM excitatory and inhibitory neurotransmitter receptor subunits.Support or Funding InformationNIH AG‐041948.

Assessment of Executive Function in Patients With Substance Use Disorder: A Comparison of Inventory- and Performance-Based Assessment

IntroductionChronic polysubstance abuse (SUD) is associated with neurophysiological and neuroanatomical changes. Neurocognitive impairment tends to affect quality of life, occupational functioning, and the ability to benefit from therapy. Neurocognitive assessment is thus of importance, but costly and not widely available. Therefore, in a busy clinical setting, procedures that include readily available measures targeting core cognitive deficits would be beneficial. This paper investigates the utility of psychometric tests and a questionnaire-based inventory to assess “hot” and “cold” neurocognitive measures of executive functions (EF) in adults with a substance use disorder. Hot decision-making processes are associated with emotional, affective, and visceral responses, while cold executive functions are associated with rational decision-making. Material and MethodsSubjects with polysubstance abuse (n=126) and healthy controls (n=32) were compared on hot (Iowa Gambling Task) and cold (Stroop and the Trail Making Test) measures of EF, in addition to a questionnaire assessing everyday EF related problems (BRIEF-A; Behavior Rating Inventory of Executive Function – Adult, self-report version). Information about the substance abuse and social adjustment were assessed by self-report. Logistic regression analyses were applied to assess independent correlates of SUD status and social adjustment. A multiple linear regression was performed to predict the number of previous treatment attempts. ResultsThe psychometric test of hot EF (the Iowa Gambling Task) did not differentiate the patients with polysubstance abuse from controls, and was not associated with social adjustment. The psychometric tests of cold EF distinguished somewhat between the groups and were associated with one indicator of social adjustment. The BRIEF-A differentiated between groups on all the clinical scales and was associated with three out of five social adjustment indicators (“criminal lifestyle,” “conflict with caregiver,” and “stable housing.”). ConclusionsThe BRIEF-A inventory was the most sensitive measure of executive function in patients with substance use disorder, followed by measures of cold executive function. BRIEF-A should therefore be considered as an integral part of the clinical routine when assessing patients with SUD.

Stigma mitigation and the importance of redundant treatments

Disgust can evoke strong behavioral responses. Sometimes these extreme visceral responses can lead to stigmatization—an overreaction to a risk. In fact, disgust may be so inhibiting that it leads people to refuse to consume completely safe items, such as treated drinking water, leading to important economic and policy implications. Using economic experiments, we provide a measure of the behavioral response to disgust. Our findings suggest that when monetary incentives are provided, the behavioral response may have been exaggerated by previous studies that have relied on survey methods. Furthermore, mitigation steps successfully reduce the stigma behavior. In fact, the results suggest that stigma is primarily reduced not by a specific mitigation step taken but by how many steps are taken consecutively. These results have important implications for policies addressing issues such as the global shortage of drinking water. Some efforts to resolve the shortage have involved recycled water that is completely safe to drink but is often rejected because of reactions of disgust.

The anatomy of Singlish: globalisation, multiculturalism and the construction of the ‘local’ in Singapore

ABSTRACTSinglish – ‘the name given to the colloquial variety of English spoken in Singapore’ [Wee, Lionel. 2014. “Linguistic Chutzpah and the Speak Good Singlish Movement.” World Englishes 33 (1): 85–99], incorporating Chinese dialect (particularly Hokkien) and Malay lexical and grammatical elements – has for some time been the antagonist in a cultural war of linguistic prescription (which has also targeted Chinese dialects) waged by the government. Some scholars have pointed out that apart from contestations about grammaticality and ‘brokenness', Singlish is also the site of contestation about identity politics in a post-colonial national setting. In more recent years, with the rise of discourses in social media critical of some government policies, as well as the increasing contestation of Singaporean identity in a transnational era, Singlish has increasingly been mobilised to mount a more grim note of sociopolitical discontent. This role is reinforced by Singlish's status as a creole of ‘the body', an affective discourse of visceral responses that thus defines an entrenched and conservative local community and identity.

The long-term functional consequences of acute infectious diarrhea.

The study reviews recent publications that build on previous studies showing that acute enteric infection can produce persistent dysfunction in the lower gut (postinfectious irritable bowel syndrome) and proximal gut (postinfectious functional dyspepsia). The review addresses risk factors, the pathophysiological basis of persistent gut dysfunction, and the factors that initiate and maintain it. Recent work has identified several loci of host genetic predisposition to these syndromes that focus attention on host immune responses that may lead to gut dysfunction, including changes in intestinal barrier function and cytokine responses to the initial infection. Human and animal studies identify changes in the serotonergic and cannabinoid pathways regulating visceral pain responses and gut motility. Recent work has also focused attention on the putative role of the intestinal microbiota or dysbiosis in maintaining gut dysfunction and this is reviewed in depth. The development of long-term consequences following an acute episode of gastroenteritis reflects a convergence of host factors that include genetic predisposition and psychological factors, as well as the development of intestinal dysbiosis. It is anticipated that future research will generate biomarkers of susceptibility as well as novel microbiota-directed preventive and therapeutic strategies.

Samedi Détente by Dorothée Munyaneza

Reviewed by: Samedi Détente by Dorothée Munyaneza Amy Swanson Samedi Détente. By Dorothée Munyaneza. Compagnie Kadidi. Under the Radar Festival, The Public Theater, New York City. January 14–17, 2016. Artists and scholars alike debate the ethics of scripting and performing trauma for spectators removed in time and space from the traumatic event. How does one encapsulate the horrors and embodied experiences of a traumatic past for the present stage? What purpose does this serve? Dorothée Munyaneza of Compagnie Kadidi, accompanied by Ivoirian dancer Nadia Beugré and French composer Alain Mahé, reconciles these debates in her multidimensional debut work, Samedi Détente. Munyaneza demonstrates how movement, sound, and language can work together to portray the multiple levels by which trauma is experienced while keeping spectators at a critical distance. Each evening from January 14th to the 17th, 2016, the trio transformed LuEsther Hall of the Public Theater in Manhattan’s East Village into a haunting reflection of the Rwandan genocide. Its title borrowed from a popular 1990s Rwandan radio program, Samedi Détente is at once chilling testimony of the genocide from Munyaneza’s perspective as a 12-year-old survivor in April 1994 and a powerful choreographic work blending an improvisational movement style with an original, live sound score. The trio repeatedly provoked the mostly white American audience to reflect on what they were doing in April 1994 while 800,000 people were killed over a hundred days in the East African country. As the house lights dimmed, Mahé set the tone of the piece when he faced the audience and unceremoniously scraped two knifes together. Following the disconcerting sound of metal against metal, Munyaneza made her way from the back of the house toward a table and microphone center stage while singing in Kinyarwanda, a Bantu language of Rwanda. Her sweet singing gradually transformed into an abrasive dance, standing on the amplified table and rhythmically pounding her feet as she assertively stared at her audience. Simultaneously, the minimal lighting revealed Beugré’s presence in the upper-left corner, a cloth covering her face. She appeared to be a specter in the background, portraying both the isolation felt by millions of Rwandans, as well as the impossibility of what the piece attempts: to aptly convey the horrors of the genocide across a significant time and space. Munyaneza’s opening song transformed into the first of several English-language monologues while Beugré’s subtle hand gestures accelerated until she pulled herself to the front of the stage in two large steps. She screamed, her shirt pulled up to cover her mouth, just as Munyaneza finished recounting the first time she bore witness to the slaughter of civilians. Munyaneza’s words dissolved into an open-mouthed silent scream, completed by Beugré’s muffled one. The piece continued in this manner: a montage of movement, song, sound, and testimony on a dimly lit stage. Although the assemblage of vignettes at times felt disjointed, Munyaneza demonstrated the potency of this combination of theatrical conventions. When words no longer sufficed, movement and sound took over, and when movement and sound did not do justice to the actual, lived horrors of her experience, the clarity of the spoken word ensured a common understanding. She recounted her disbelief of the atrocities committed by the Hutu majority, named several individuals who lost their lives, and denounced nuns, priests, and former French president François Mitterrand for their complicity and participation. Her words, spoken plainly to the audience, gave these details the clarity and bluntness they deserve. Yet, when the events she described entered the realm of the ineffable, Munyaneza seamlessly slipped into song or dance, her body tense, her muscles contracted as her torso jutted forward over bent, turned-in legs, accompanied by Mahé’s composition of rattling pots and knives striking wood. Click for larger view View full resolution Nadia Beugré in Samedi Détente. (Photo: Laura Fouqueré.) As a dance practitioner I felt an especially visceral response to the movement phrases, many of which I would have liked to continue longer. Beugré, an accomplished choreographer and dancer, performed some of the most compelling movement phrases. Her role shifted throughout the...

What shapes perceptions of climate change? New research since 2010

Five years ago, an article in the first issue of WIREs Climate Change reviewed the factors that shape perceptions of climate change. Climate change is an abstract statistical phenomenon, namely a slow and gradual modification of average climate conditions, and thus a difficult phenomenon to detect and assess accurately based on personal experience. The current update of the original article—‘new research since 2010’—revisits topics covered in the original contribution: the role of personal experience with climate change, in particular extreme weather events; the effects of psychological distance on climate change perception and action; the effects of political ideology, age, gender, and nationality, and situational influences; and the role of different processing modes in climate change perception and the low level of visceral response (dread) associated with climate change risks. In addition, the current article also addresses new topics since 2010: attribute substitution or the use of weather anomalies—‘local’ warming or cooling—when judging the likelihood of global warming; the effects of different labels for the phenomenon—global warming versus climate change—on perceptions of its likelihood and importance; and the effect and role of uncertainty about different aspects of climate change and its consequences and how it is communicated on perceptions and actions. WIREs Clim Change 2016, 7:125–134. doi: 10.1002/wcc.377This article is categorized under: Perceptions, Behavior, and Communication of Climate Change > Perceptions of Climate Change

The state of sleep and the current brain paradigm.

Up to the present time cerebral cortex was considered as substrate for realization of the highest psychical functions including consciousness. Cortical sensory areas were regarded as structures specialized for processing of information coming from one particular modality (visual, auditory, somatosensory, and so on). However, studies of cortical activity in sleep-wake cycle demonstrated that during sleep the same neurons in the same cortical areas switch to processing of signals coming from the various visceral systems. After awakening these visceral responses disappear and the neurons return to processing of the information coming from the exteroreceptors. These observations indicate that most likely cortical areas are universal processors, which perform particular operations with incoming information independent of its origin. During wakefulness, results of the information processing on the cortical level should be directed to structures connected with organization of behavior and consciousness, while during sleep cortical outputs should be redirected to structures performing integration of the visceral information. Thus, results of sleep studies indicate that current brain paradigm should be changed.

Visceral Hypersensitivity and Altered Colonic Motility in Type 2 Diabetic Rat.

Background/AimsAbnormal visceral sensitivity and disordered motility are common in patients with diabetes mellitus. The purpose of the present study was to investigate whether visceral sensation and bowel motility were altered in a rat model of type 2 diabetes mellitus accompanied by weight loss.MethodsA type 2 diabetic rat model in adulthood was developed by administrating streptozotocin (STZ; 90 mg/kg, i.p.) to neonatal rats. Eight weeks after STZ administration, rats with blood glucose level of 200 mg/dL or higher were selected and used as diabetic group (n = 35) in this study. Abdominal withdrawal reflex and arterial pulse rate were measured to examine visceral nociception induced by colorectal distension (0.1–1.0 mL). The amplitude, frequency, and area under the curve (AUC) of spontaneous phasic contractions of colonic circular muscles were recorded in vitro to examine colonic motility.ResultsSTZ-treated diabetic rats gained significantly less weight for 8 weeks than control (P < 0.01). Forty-eight percent of the diabetic rats showed enhanced visceral nociceptive response to colorectal distension. Diabetic rats did not differ from control rats in colorectal compliance. However, the frequency and AUC, not the amplitude, of colonic spontaneous contraction in vitro was significantly decreased in diabetic rats compared to control rats (P < 0.01 in frequency and P < 0.05 in AUC).ConclusionsThese results demonstrate visceral hypersensitivity and colonic dysmotility in a rat model of type 2 diabetes mellitus accompanied by weight loss.

Art expertise modulates the emotional response to modern art, especially abstract: an ERP investigation.

Art is one of life’s great joys, whether it is beautiful, ugly, sublime or shocking. Aesthetic responses to visual art involve sensory, cognitive and visceral processes. Neuroimaging studies have yielded a wealth of information regarding aesthetic appreciation and beauty using visual art as stimuli, but few have considered the effect of expertise on visual and visceral responses. To study the time course of visual, cognitive and emotional processes in response to visual art we investigated the event-related potentials (ERPs) elicited whilst viewing and rating the visceral affect of three categories of visual art. Two groups, artists and non-artists viewed representational, abstract and indeterminate 20th century art. Early components, particularly the N1, related to attention and effort, and the P2, linked to higher order visual processing, was enhanced for artists when compared to non-artists. This effect was present for all types of art, but further enhanced for abstract art (AA), which was rated as having lowest visceral affect by the non-artists. The later, slow wave processes (500–1000 ms), associated with arousal and sustained attention, also show clear differences between the two groups in response to both type of art and visceral affect. AA increased arousal and sustained attention in artists, whilst it decreased in non-artists. These results suggest that aesthetic response to visual art is affected by both expertise and semantic content.

Accuracy of Tokuhashi score system in predicting survival of lung cancer patients with vertebral metastasis.

Controversy exists in the accuracy of Tokuhashi score (TS) system in predicting survival of patients with vertebral metastasis, including vertebral metastases from primary lung cancer. To calculate the accuracy of the TS in predicting survival of lung cancer patients with vertebral metastasis and investigate which subgroup's survival is suitable for TS to predict, we conduct this retrospective study. From January 2008 to December 2013, 151 patients with vertebral metastases from primary lung cancer in our institute were included. The data were censored at December 2014. Patients were classified according to TS. The actual and predicted survivals were compared to calculate the accuracy rate. Spearman's correlation analysis was conducted to explore the relation between overall survival and TS. Cox regression was carried out to investigate potential factors affecting prognosis. Only 8.6 % (13 patients) actually followed the survivorship pattern as predicted by the TS. Spearman's correlation analysis demonstrated that actual overall survival correlated significantly with the TS. Cox model indicated that status of visceral metastases (i.e., none, involved with lung, involved with extrapulmonary organ) and response to first-time systemic therapy (effective or not) are associated significantly with overall survival. For patients with visceral metastases and progression to first-time systemic therapy simultaneously, predicted survival by TS and actual survival matched well. TS could only predict survival accurately in those with visceral metastases and disease progression to first-time systemic therapy simultaneously. Thus, it may not be a reliable tool to predict survival in lung cancer patients with vertebral metastasis. Status of visceral metastases and response to first-time systemic therapy should be added into TS system to increase validity and accuracy.

Medication safety strategies worth sharing with hospital pharmacists

Improving medication safety is at the forefront of most hospital pharmacists'minds. This complex issue has numerous facets and nuances,and nearly endless opportunities for pharmacists to jump in and makeinterventions that change hospital policy resulting in better, safer care.

Review: Mackintosh Architecture and Mackintosh Architecture

Mackintosh Architecture Hunterian Art Gallery, University of Glasgow 18 July 2014–4 January 2015 Architecture Gallery, Royal Institute of British Architects, London 18 February–23 May 2015 When fire ripped through the Glasgow School of Art (GSA) in May 2014, gutting the library and destroying original furniture and fittings, the visceral response revealed just how strong a place Charles Rennie Mackintosh holds in the affections of Glasgow, Scotland, and the wider world. His name is now almost synonymous with Glasgow, and his designs market the city, inspired by and promoting romantic notions of the lone genius. An exhibition that opened less than three months later at the Hunterian Art Gallery aimed for a more nuanced account of Mackintosh’s work as an architect than the now well-defined “Mackintosh myth” allows, revealing some of the results of an important four-year research project, funded by the Arts and Humanities Research Council and triumphantly concluded in 2014 with the launch of a website (http://www.mackintosh-architecture.gla.ac.uk). This extraordinarily rich, multilayered resource was the major product of the research, and the exhibition was designed to highlight its findings and draw attention to its value for future inquiry. Toward the end of the show a wall text modestly noted there were no major new discoveries, but the importance of the project was that, while acknowledging the individuality of Mackintosh’s vision, it provided a corrective to the popular image by laying out evidence of his work as part of a partnership and demonstrating the collaborative nature of most architectural practice. There had not been a dedicated …

Assessment of visceral pain associated with metritis in dairy cows

Metritis is a common disease in dairy cattle, but to our knowledge, no work has assessed pain associated with this disease. Tissue palpation is commonly used to assess pain in human and veterinary medicine. The objective of this study was to evaluate visceral pain responses during rectal palpation, with and without uterine palpation, in healthy cows and in cows diagnosed with metritis. A total of 49 Holstein dairy cows (mean ± standard deviation parity of 2.8±1.8) were subjected to systematic health checks every 3 d after parturition for 21 d, scoring for vaginal discharge (0 to 4); 13 cows showed a discharge score ≥2 during at least 1 health check and were classified as metritic, whereas 29 cows were classified as healthy and showed no sign of this or any other disease (including mastitis and lameness). Back arch and heart rate variability before examination and during palpation were recorded using video and heart rate monitors. Back arch (cm2) on the day of diagnosis was greater in metritic versus healthy cows (1,034±72 vs. 612±48cm2), and greater during rectal palpation with uterine palpation versus rectal palpation without uterine palpation (869±45 vs. 777±45cm2). Heart rate frequency domain analysis showed that the low-frequency portion was higher in cows with metritis versus healthy cows (16.5±1.2 vs. 12.9±1.0). Time domain analysis showed that the standard deviation between normal to normal interbeat intervals and the root mean square of successive differences both decreased during rectal palpation with uterine palpation versus rectal palpation without uterine palpation (1.9±0.1 vs. 2.5±0.1 and 1.3±0.1 vs. 1.7±0.1, respectively). Together, these results indicate that the inflammation associated with metritis is painful, and that the pain response can be detected during rectal palpation with and without uterine palpation. Rectal palpation with uterine palpation appears to be more aversive than rectal palpation without uterine palpation, suggesting that the former should be avoided when possible.

Abstract OT2-2-03: MERIBEL study: Efficacy of eribulin in first line of taxane-resistant patients with HER2 negative metastatic breast cancer

Abstract Brief background discussion: Eribulin is a nontaxane microtubule dynamics inhibitor. It has shown a significant benefit in overall survival in patients with metastatic breast cancer (MBC) that underwent treatments in multiple previous lines (Cortes et al. 2009). However, little is known about the activity of the drug in patients with taxane-resistant early advanced disease. This trial is designed to determine the safety and efficacy of Eribulin as single first line agent in the treatment of patients with HER2(-) MBC deemed resistant to taxanes. Trial design: This study is a Phase IIa, multicenter, open-label, single-arm in patients with HER2 (-) metastatic breast cancer clinical trial. The scheme consists in the administration of 1,23 mg/m2 of Eribulin (equivalent to 1.4mg/m2 eribulin mesylate) as single agent the days 1 and 8 of each 21 days of the cycle, until progression of illness, unacceptable toxicity level or investigator’s criteria. The study was approved by the competent authorities and Ethics committees from 14 participating centers in Spain and Portugal. Eligibility criteria: The principal inclusion and exclusion criteria were: (1) Patients with MBC that have not received prior chemotherapy for Advanced disease; (2) Previous chemotherapy for early stages (I-IIIB) including taxanes (paclitaxel and/or docetaxel) for at least 4 cycles; (3) Less than 36 months* between the last cycle with taxanes and metastatic relapse; (4) Evaluable disease under RECIST criteria; (5) Absence of HER2 over-expression (IHQ of 0/1 or negative FISH/CISH); (6) Absence of neurotoxicity &amp;gt; G1. (*) Amended to 48 months (Llombart et al. ASCO 2013). Specific aims: The main objective is to determine the efficacy of Eribulin as single first line agent in the treatment of patients with HER2-negative MBC and taxanes resistant criteria. Secondary objectives are: Estimate the tolerance to the treatment; assess the clinical response of the study treatment by RECIST criteria; correlate hormone receptor status (+/-) with clinical response and tolerability; identify the relationship between presence of visceral disease and response to therapy. Statistical Methods: The primary endpoint is time to progression (TTP). Secondary endpoints include the safety of treatment, clinical benefit rate, objective response, progression-free survival and overall survival. A total of 60 patients were predefined for the primary outcome. The sample size is based on a one-arm survival design. We test the null hypothesis that true TTP is 3.7 versus the alternative hypothesis (H1) that TTP is 5.5 months. An interim analysis with 30 patients completed has been planned. The study will be stopped for futility or efficacy if conditional power is less than 20% or more than 80%, respectively. Type I and II error assumed were 5% one-sided and 16%, respectively. Present accrual: Currently, 16 women have been recruited for the trial since study start in July 2013. The expected end of accrual will be on March 2015. Contact information for people with a specific interest in the trial: Maria Campos (maria.campos@medsir.org) Scientific director Medica Scientia Innovation Research (MedSIR ARO). Citation Format: Vanessa Ortega, María Martínez, Antonio Antón, Isabel Garau, Lourdes Calvo, Esperanza Blanco, Yolanda Fernández, José Juan Illarramendi, Mirta García, Antonio Llombart, Javier Cortés. MERIBEL study: Efficacy of eribulin in first line of taxane-resistant patients with HER2 negative metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT2-2-03.

Theta-frequency phase-locking of single anterior cingulate cortex neurons and synchronization with the medial thalamus are modulated by visceral noxious stimulation in rats

The rodent anterior cingulate cortex (ACC) is critical for visceral pain and pain-related aversive response in chronic visceral hypersensitive (VH) state. Long-term potentiation (LTP), induced by theta burst stimulation (TBS) in the medial thalamus (MT)-ACC pathway, is blocked in VH rats. However, the neuronal intrinsic firing characteristics and the MT-ACC connectivity have not been investigated in visceral pain.Using repetitive distension of the colon and rectum (rCRD) as a sensitization paradigm, we have identified that the spontaneous firing rates of ACC neurons and the CRD-stimulated neuronal firings were increased after repetitive visceral noxious stimulation. This correlates with increases in visceral pain responses (visceromotor responses, VMRs).Two multichannel arrays of electrodes were implanted in the MT and ACC. Recordings were performed in free-moving rats before and after repeated CRD treatment. Power spectral density analysis showed that the local field potential (LFP) recorded in the ACC displayed increases in theta band power (4–10Hz) that were modulated by rCRD. Neural spike activity in the ACC becomes synchronized with ongoing theta oscillations of LFP. Furthermore, cross correlation analysis showed augmented synchronization of thalamo-ACC theta band LFPs, which was consistent with an increase of neuronal communication between the two regions.In conclusion, these results reveal theta oscillations and theta-frequency phase-locking as prominent features of neural activity in the ACC and a candidate neural mechanism underlying acute visceral pain.

Épines irritatives et hyperactivité vésicale neurologique

Describe the relationships between neurogenic overactive bladder and noxious stimuli. Relevant data from the literature were identified primarily through a Medline search of articles published through July 2014. The search terms included overactive bladder, central nervous system, noxious visceral and cutaneous stimuli. Overactive bladder often due to overactive detrusor is the most common symptom observed in central neurogenic bladder (70 to 80% in case of spinal cord injury). Pathophysiological mechanisms are various and numerous. Noxious cutaneous stimuli may determine, or maintain, these symptoms by increased afferent inputs in segmental levels, particularly S2S3 levels, determining exaggerated visceral, muscle and bladder responses depending on this considered medullary level. These modifications are only observed in case of central neurogenic lesions secondary to spinal cord involvement. Animal researches have precised the role of lack of the supra-segmental inhibition. In presence of neurogenic overactive bladder, it is always necessary to track down noxious stimuli particularly in case of modifications of clinical or urodynamic status or when the usual treatments, generally anticholinergic drugs, have a reduced efficacy. Treatment is first focused on the suppression of these noxious cutaneous stimuli.

Chitinase 3-like-1 regulates both visceral fat accumulation and asthma-like Th2 inflammation.

Obesity, especially truncal obesity, is a risk factor for asthma incidence, prevalence, and severity. Chitinase 3-like-1 (Chi3l1) is an evolutionarily conserved moiety that plays a critical role in antipathogen and Th2 responses. However, the mechanisms that underlie the association between asthma and obesity and the role(s) of Chi3l1 in fat accumulation have not been defined. To determine whether Chi3l1 is regulated by a high-fat diet (HFD) and simultaneously plays an important role(s) in the pathogenesis of asthma and obesity. We evaluated the regulation of Chi3l1 by an HFD and Th2 inflammation. We also used genetically modified mice to define the roles of Chi3l1 in white adipose tissue (WAT) accumulation and Th2 inflammation and blockers of sirtuin 1 (Sirt1) to define its roles in these responses. Finally, the human relevance of these findings was assessed with a case-control study involving obese and lean control subjects and those with asthma. These studies demonstrate that an HFD and aeroallergen challenge augment the expression of WAT and pulmonary Chi3l1. Chi3l1 also played a critical role in WAT accumulation and lung Th2 inflammation. In addition, Chi3l1 inhibited Sirt1 expression, and the deficient visceral fat and Th2 responses in Chi3l1 null mice were reversed by Sirt1 inhibition. Finally, serum and sputum Chi3l1 were positively associated with truncal adiposity, and serum Chi3l1 was associated with persistent asthma and low lung function in obese subjects with asthma. Chi3l1 is induced by an HFD and Th2 inflammation, and simultaneously contributes to the genesis of obesity and asthma.

Tu1876 Chronic Stress-Induced Visceral Hyperalgesia: Evidence for Differential Effects of Lubiprostone on Tight Junction Protein Expression in the Colon

Introduction: In humans, chronic psychological stress is associated with increased intestinal permeability and visceral hyperalgesia, which is recapitulated in the chronic intermittent water avoidance stress (WAS) rat model. Previously, we reported that WAS rats demonstrated increased intestinal permeability for macromolecules specifically in the colon, which correlated with reduced epithelial tight junction protein expression in the colon epithelium. Lubiprostone (Lub), a prostaglandin receptor agonist used to treat chronic constipation and IBS-C, has been shown to restore barrier function and epithelial tight junction protein expression in the ischemic porcine intestine. Hypothesis: Lub treatment ameliorates increased colon permeability and visceral hyperalgesia in the WAS rat model. Methods: Male Sprague Dawley rats were subjected to one hour of WAS for 10 consecutive days with or without oral administration of Lub. A 20 μg/kg/day dose of Lub was chosen based on a dose response study. On day 11, visceral motor response (VMR) to colorectal distention (CRD) or colon permeability were measured. Permeability was assayed by measuring plasma levels of the non-ionic molecule FITC-Dextran (4KDa), which was given by gavage at 400 mg/Kg. Distal colon tissue was used for Western blot analysis. Results: WAS was associated with increased colon permeability compared to controls in 7 of 14 rats (p = 0.0036) and a decrease in the level of the epithelial tight junction protein occludin (p < 0.05). Lub prevented the stress-induced increase in colon permeability (p = 0.01), as well as the decrease in occludin. WAS rats had a significant increase in pellet output over controls (p < 0.0001), however there were no significant difference in pellet output between Lub treated and untreated WAS rats. All WAS rats showed visceral hyperalgesia in response to CRD (60 mmHg, p < 0.0001) in comparison to controls. Lub treatment of WAS rats prevented visceral hyperalgesia in response to CRD for 7 out of 14 rats (p < 0.0001), whereas the other 7 had VMR to CRD levels equivalent to untreated WAS rats. Conclusion: Lub prevents WASassociated: 1) decrease in epithelial tight junction protein expression in a subset of rats that showed an increase in colon permeability and 2) hyperalgesia in a subset of rats, despite genetic homogeneity. We hypothesize that increased gut permeability and hyperalgesia in response to WAS are linked, and the differential effects of WAS on colon permeability and Lub treatment on visceral hyperalgesia reflects differences in epigenetic regulation of relevant target genes.

Tu1875 BDNF Regulates NMDA Receptor Phosphorylation via the PLC/PKC Pathway in the Spinal Cord During Colitis

Introduction: In humans, chronic psychological stress is associated with increased intestinal permeability and visceral hyperalgesia, which is recapitulated in the chronic intermittent water avoidance stress (WAS) rat model. Previously, we reported that WAS rats demonstrated increased intestinal permeability for macromolecules specifically in the colon, which correlated with reduced epithelial tight junction protein expression in the colon epithelium. Lubiprostone (Lub), a prostaglandin receptor agonist used to treat chronic constipation and IBS-C, has been shown to restore barrier function and epithelial tight junction protein expression in the ischemic porcine intestine. Hypothesis: Lub treatment ameliorates increased colon permeability and visceral hyperalgesia in the WAS rat model. Methods: Male Sprague Dawley rats were subjected to one hour of WAS for 10 consecutive days with or without oral administration of Lub. A 20 μg/kg/day dose of Lub was chosen based on a dose response study. On day 11, visceral motor response (VMR) to colorectal distention (CRD) or colon permeability were measured. Permeability was assayed by measuring plasma levels of the non-ionic molecule FITC-Dextran (4KDa), which was given by gavage at 400 mg/Kg. Distal colon tissue was used for Western blot analysis. Results: WAS was associated with increased colon permeability compared to controls in 7 of 14 rats (p = 0.0036) and a decrease in the level of the epithelial tight junction protein occludin (p < 0.05). Lub prevented the stress-induced increase in colon permeability (p = 0.01), as well as the decrease in occludin. WAS rats had a significant increase in pellet output over controls (p < 0.0001), however there were no significant difference in pellet output between Lub treated and untreated WAS rats. All WAS rats showed visceral hyperalgesia in response to CRD (60 mmHg, p < 0.0001) in comparison to controls. Lub treatment of WAS rats prevented visceral hyperalgesia in response to CRD for 7 out of 14 rats (p < 0.0001), whereas the other 7 had VMR to CRD levels equivalent to untreated WAS rats. Conclusion: Lub prevents WASassociated: 1) decrease in epithelial tight junction protein expression in a subset of rats that showed an increase in colon permeability and 2) hyperalgesia in a subset of rats, despite genetic homogeneity. We hypothesize that increased gut permeability and hyperalgesia in response to WAS are linked, and the differential effects of WAS on colon permeability and Lub treatment on visceral hyperalgesia reflects differences in epigenetic regulation of relevant target genes.