Estrogen augmented visceral pain and colonic neuron modulation in a double-hit model of prenatal and adult stress.

Background: Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent way. Combining adult stress in offspring will increase this sensitivity. Based on the evidence implicating estrogen in exacerbating visceral hypersensitivity in female rodents in preclinical models, we predicted that chronic prenatal stress (CPS) + chronic adult stress (CAS) will maximize visceral hyperalgesia; and that estrogen plays an important role in colonic hyperalgesia.

Estrogen and serotonin enhance stress-induced visceral hypersensitivity in female rats by up-regulating brain-derived neurotrophic factor in spinal cord.

Background: We previously reported that female offspring of dams subjected to chronic prenatal stress (CPS) develop enhanced visceral hypersensitivity (VHS) following exposure to chronic stress in adult life that is mediated by up-regulation of spinal cord BDNF. The aims of this study were to examine the roles of estrogen receptor alpha (ERα) and an increase in spinal serotonin signaling in promoting this enhanced VHS in female rats and up-regulation of spinal cord BDNF transcription.

Methods: Pregnant dams were exposed to chronic stress from E11 until delivery.

Neonatal Injury Increases Gut Permeability by Epigenetically Suppressing E-Cadherin in Adulthood.

Altered intestinal epithelial integrity is an important susceptibility trait in inflammatory bowel disease (IBD), and early life stressors are reported to contribute to this disease susceptibility in adulthood. To identify disease mechanisms associated with early-life trauma that exacerbate IBD in adulthood, we used a "double-hit" neonatal inflammation (NI) and adult inflammation (AI) model that exhibits more severe mucosal injury in the colon later in life. In this study, we explore the underlying mechanisms of this aggravated injury.

Neonatal Colonic Inflammation Epigenetically Aggravates Epithelial Inflammatory Responses to Injury in Adult Life.

Background & Aims: Early life adversity is considered a risk factor for the development of gastrointestinal diseases, including inflammatory bowel disease. We hypothesized that early life colonic inflammation causes susceptibility to aggravated overexpression of interleukin (IL)1β.

Methods: We developed a 2-hit rat model in which neonatal inflammation (NI) and adult inflammation (AI) were induced by trinitrobenzene sulfonic acid.

Impaired Interoception in a Preclinical Model of Functional Dyspepsia.

Introduction: The etiologies of functional dyspepsia symptoms, including postprandial distress syndrome, remain unknown. We tested the hypothesis that neonatal colon inflammation induces postprandial distress syndrome-like symptoms in adult life that associate with increased activation of vagal afferent pathways and forebrain limbic regions.

Results: These rats showed a significant decrease in nutrient meal consumption to satiety after an overnight fast, decrease in gastric emptying, decrease in total distance traveled, and decrease in percent distance traveled in midfield versus control rats in open field test, indicating postprandial anxiety- and depression-like behaviors.

Enhanced sympathetic nerve activity induced by neonatal colon inflammation induces gastric hypersensitivity and anxiety-like behavior in adult rats.

Gastric hypersensitivity (GHS) and anxiety are prevalent in functional dyspepsia patients; their underlying mechanisms remain unknown largely because of lack of availability of live visceral tissues from human subjects. Recently, we demonstrated in a preclinical model that rats subjected to neonatal colon inflammation show increased basal plasma norepinephrine (NE), which contributes to GHS through the upregulation of nerve growth factor (NGF) expression in the gastric fundus. We tested the hypothesis that neonatal colon inflammation increases anxiety-like behavior and sympathetic nervous system activity, which upregulates the expression of NGF to induce GHS in adult life.

Noninflammatory upregulation of nerve growth factor underlies gastric hypersensitivity induced by neonatal colon inflammation.

Gastric hypersensitivity is one of the key contributors to the postprandial symptoms of epigastric pain/discomfort, satiety, and fullness in functional dyspepsia patients. Epidemiological studies found that adverse early-life experiences are risk factors for the development of gastric hypersensitivity. Preclinical studies found that neonatal colon inflammation elevates plasma norepinephrine (NE), which upregulates expression of nerve growth factor (NGF) in the muscularis externa of the gastric fundus.

Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation.

Psychological disorders are prevalent in patients with inflammatory bowel disease; the underlying mechanisms remain unknown. We tested the hypothesis that ulcerative colitis-like inflammation induced by dextran sodium sulfate (DSS) exacerbates the ongoing spontaneous activity in colon-projecting afferent neurons that induces abdominal discomfort and anxiety, and depressive-like behaviors in rats. In this study, we used the conditioned place preference and standard tests for anxiety- and depression-like behaviors.

Inflammation induced by mast cell deficiency rather than the loss of interstitial cells of Cajal causes smooth muscle dysfunction in W/W(v) mice.

The initial hypothesis suggested that the interstitial cells of Cajal (ICC) played an essential role in mediating enteric neuronal input to smooth muscle cells. Much information for this hypothesis came from studies in W/W(v) mice lacking ICC. However, mast cells, which play critical roles in regulating inflammation in their microenvironment, are also absent in W/W(v) mice.

Are interstitial cells of Cajal involved in mechanical stress-induced gene expression and impairment of smooth muscle contractility in bowel obstruction?

Background And Aims: The network of interstitial cells of Cajal (ICC) is altered in obstructive bowel disorders (OBD). However, whether alteration in ICC network is a cause or consequence of OBD remains unknown. This study tested the hypothesis that mechanical dilation in obstruction disrupts the ICC network and that ICC do not mediate mechanotranscription of COX-2 and impairment of smooth muscle contractility in obstruction.

Developmental origins of colon smooth muscle dysfunction in IBS-like rats.

Epidemiological studies show that subsets of adult and pediatric patients with irritable bowel syndrome (IBS) have prior exposures to psychological or inflammatory stress. We investigated the cellular mechanisms of colonic smooth muscle dysfunction in adult rats subjected to neonatal inflammation. Ten-day-old male rat pups received 2,4,6-trinitrobenzene sulfonic acid to induce colonic inflammation.

Paradoxical regulation of ChAT and nNOS expression in animal models of Crohn's colitis and ulcerative colitis.

Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel disease. We examined the effects of inflammation on the expression of choline acetyltransferase (ChAT) and nNOS in the muscularis externae of two models of colonic inflammation, trinitrobenzene sulfonic acid (TNBS)-induced colitis, which models Crohn's disease-like inflammation, and DSS-induced colitis, which models ulcerative Colitis-like inflammation. In TNBS colitis, we observed significant decline in ChAT, nNOS, and protein gene product (PGP) 9.

Developmental origins of functional dyspepsia-like gastric hypersensitivity in rats.

Background & Aims: Gastric hypersensitivity (GHS) contributes to epigastric pain in patients with functional dyspepsia (FD); the etiology and cellular mechanisms of this dysfunction remain unknown. We investigated whether inflammatory insult to the colons of neonatal rats induced GHS in adult life.

Methods: We used cellular, molecular, and in vivo approaches to investigate the mechanisms of GHS in adult rats subjected to neonatal colonic insult by intraluminal administration of trinitrobenzene sulfonic acid; controls received saline.

Differential immune and genetic responses in rat models of Crohn's colitis and ulcerative colitis.

Crohn's disease and ulcerative colitis are clinically, immunologically, and morphologically distinct forms of inflammatory bowel disease (IBD). However, smooth muscle function is impaired similarly in both diseases, resulting in diarrhea. We tested the hypothesis that differential cellular, genetic, and immunological mechanisms mediate smooth muscle dysfunction in two animal models believed to represent the two diseases.

Adrenergic stimulation mediates visceral hypersensitivity to colorectal distension following heterotypic chronic stress.

Background & Aims: Chronic stress exacerbates or causes relapse of symptoms such as abdominal pain and cramping in patients with irritable bowel syndrome. We investigated whether chronic stress increases plasma norepinephrine and sensitizes colon-specific dorsal root ganglion (DRG) neurons by increasing expression of nerve growth factor (NGF) in the colon wall.

Methods: Heterotypic chronic stress (HeCS) was applied to male Wistar rats and neurologic and molecular responses were analyzed.

The endogenous hydrogen sulfide producing enzyme cystathionine-beta synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome.

Background: The pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS), remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S) in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-beta-synthetase (CBS) in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH).

A rat model of chronic gastric sensorimotor dysfunction resulting from transient neonatal gastric irritation.

Background & Aims: Although several pathophysiologic abnormalities have been noted in functional dyspepsia (FD), their pathogenesis is poorly understood. We hypothesized that chronic gastric hypersensitivity and gastric motor dysfunction seen in FD patients can be modeled in rats by transient gastric irritation during the neonatal period, a time of known neuronal vulnerability to long-term plasticity.

Methods: Ten-day-old male rats received 0.

Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis.

Background & Aims: The neurobiologic basis of pancreatic hyperalgesia in chronic pancreatitis (CP) is understood poorly and there is a need to identify novel therapeutic targets. Our aim was to study the role of the transient receptor potential vanilloid 1 (TRPV1), a key integrator of noxious stimuli, in the pathogenesis of pancreatic pain in a rat model of CP.

Methods: CP was induced in rats by intraductal injection of trinitrobenzene sulfonic acid.

The ClC-3 chloride transport protein traffics through the plasma membrane via interaction of an N-terminal dileucine cluster with clathrin.

ClC-3 is a ubiquitously expressed chloride transport protein that is present in synaptic vesicles and endosome/lysosome compartments. It is largely intracellular but has been observed at the plasma membrane as well. The aim of this study was to identify the pathways and regulation of ClC-3 trafficking to intracellular sites.

A computerized analysis of robotic versus laparoscopic task performance.

Introduction: Robotic technology has been postulated to improve performance in advanced surgical skills. We utilized a novel computerized assessment system to objectively describe the technical enhancement in task performance comparing robotic and laparoscopic instrumentation.

Methods And Procedures: Advanced laparoscopic surgeons (2-10 yrs experience) performed three unique task modules using laparoscopic and Telerobotic surgical instrumentation (Intuitive Surgical, Sunnyvale, CA).

Hirschsprung's disease in a young adult: report of a case and review of the literature.

Hirschsprung's disease (HD) in adults is rare and often undiagnosed or misdiagnosed. We report a case of HD in a 26-year-old woman who had a history of chronic constipation that required laxatives and enemas since early childhood. She developed severe intestinal obstruction and presented to the emergency department with significant abdominal distension.

Enhanced excitability and suppression of A-type K+ current of pancreas-specific afferent neurons in a rat model of chronic pancreatitis.

Chronic pancreatitis (CP) is a relatively common disorder, characterized by glandular insufficiency and chronic, often intractable, pain. The mechanism of pain in CP is poorly understood. We have previously developed a model of trinitrobenzene sulphonic acid (TNBS)-induced CP that results in nociceptive sensitization in rats.