New neostigmine-based behavioral mouse model of abdominal pain.

BACKGROUND: Animal models of visceral pain have gained much attention as an important tool to elucidate the possible mechanisms underlying functional gastrointestinal (GI) disorders. Here we report the development of a new, minimally invasive behavioral model of abdominal pain induced by ip administration of neostigmine in mice. METHODS: Spontaneous behavioral responses evoked by ip injection of neostigmine were compared to pain-related behaviors induced by acetic acid solution (ip), mustard oil (MO) and capsaicin (both ic). Pain behaviors were quantified by assessment of defined postures (licking of the abdomen, stretching, squashing of the abdomen and abdominal contractions). Neuronal activation of spinal cord was measured by determining the number of c-Fos-positive cells. RESULTS: Neostigmine (2.5 µg/kg, ip), acetic acid solution (ip), MO and capsaicin (both ic) induced spontaneous behavioral responses in mice, which were blocked by morphine (3 mg/kg, ip), suggesting the involvement of pain signaling pathways. Injection of neostigmine enhanced c-Fos expression in spinal cord neurons. CONCLUSION: The neostigmine model represents a new minimally invasive mouse model to study visceral pain. Based on the neuronal activation pattern in the spinal cord we suggest that this model may be used to study abdominal pain signaling pathways in the GI tract.

Juvenile polyposis of the stomach--a novel cause of hypergastrinemia.

BACKGROUND: A 38-year-old female presented with a 3-year history of postprandial abdominal pain, refractory nausea, vomiting and hematemesis. She appeared malnourished and her symptoms were refractory to previous treatment with acid-suppressive drugs, prokinetics and antiemetics. Her medical history was significant for a diagnosis of juvenile polyposis syndrome at the age of 14 resulting in a transverse colectomy, and a diagnosis of Crohn's disease in her residual colon at the age of 35 resulting in a total colectomy. INVESTIGATIONS: Physical examination, blood analysis, esophagogastroduodenoscopy with biopsy, abdominal endoscopic ultrasound, abdominal CT scan, MRI, 24 h urine analysis, MIBG scintigraphy, ocreotide scintigraphy, fluorodeoxyglucose-PET scan and genetic testing for defined polyposis syndromes (SMAD4, BMPR1A). DIAGNOSIS: Juvenile polyposis syndrome with outlet obstruction of the stomach and excessive hypergastrinemia. MANAGEMENT: Continuous acid-suppressive therapy, prokinetic therapy and total parenteral nutrition. Repetitive endoscopic polypectomy (also known as debulking) was performed twice and was followed by gastrectomy with duodenoesophageal anastomosis.

Microscopic colitis -- a common cause of diarrhoea in older adults.

Diarrhoeal diseases are common in older populations and often markedly affect their quality of life. Although there are numerous potential causes, microscopic colitis (MC) is increasingly recognised as a major diagnostic entity in older individuals. MC is comprised of two distinct histological forms - collagenous colitis and lymphocytic colitis, both of which frequently occur in older populations. Recent studies suggest that between 10 and 30% of older patients investigated for chronic diarrhoea with an endoscopically normal appearing colon will have MC. It is unclear why MC is more common in older populations, but it is associated with both autoimmune disorders and several drugs that are commonly used by seniors. A definitive diagnosis can only be made with colonic biopsies. Since MC was first described in 1976 and only recently recognised as a common cause of diarrhoea, many practising physicians may not be aware of this entity. In this review, we outline the epidemiology, risk factors associated with MC, its pathophysiology, the approach to diagnosis and the management of these individuals.

Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors.

The endocannabinoid (EC) system mediates protection against intestinal inflammation. In this study, we investigated the effects of blocking EC degradation or cellular reuptake in experimental colitis in mice. Mice were treated with trinitrobenzene-sulfonic acid in presence and absence of the fatty acid amide hydrolase (FAAH) blocker URB597, the EC membrane transport inhibitor VDM11, and combinations of both. Inflammation was significantly reduced in the presence of URB597, VDM11, or both as evaluated by macroscopic damage score, myeloperoxidase levels, and colon length. These effects were abolished in CB(1)- and CB(2)-receptor-gene-deficient mice. Quantitative reverse transcription polymerase chain reaction after induction of experimental colitis by different pathways showed that expression of FAAH messenger RNA (mRNA) is significantly reduced in different models of inflammation early in the expression of colitis, and these return to control levels as the disease progresses. Genomic DNA from 202 patients with Crohn's disease (CD) and 206 healthy controls was analyzed for the C385A polymorphism in the FAAH gene to address a possible role in humans. In our groups, the C385A polymorphism was equally distributed in patients with CD and healthy controls. In conclusion, drugs targeting EC degradation offer therapeutic potential in the treatment of inflammatory bowel diseases. Furthermore, reduction of FAAH mRNA expression is involved in the pathophysiological response to colitis.