Willemijntje A. Hoogerwerf

Rabbit NHE2 and NHE3 are two epithelial isoform Na+/H+ exchangers (NHE), the messages for which are found predominantly and entirely, respectively, in renal, intestinal, and gastric mucosa. The current studies used Western analysis and immunohistochemistry to identify and characterize the apical vs. basolateral membrane distribution of NHE2 and NHE3 in intestinal epithelial cells. Based on Western analysis, NHE2 and NHE3 both are present in brush-border but not basolateral membranes of small intestine. Both NHE2 and NHE3 are 85-kDa proteins. Consistent with Western analysis, NHE2 and NHE3 are immunolocalired to the brush-border but not basolateral membranes of villus epithelial cells, but not goblet cells, in human jejunum and ileum and in surface epithelial cells in the ascending and descending colon and rectum. In addition, NHE2 and NHE3 are present in small amounts in the crypt cell brush border of human jejunum, ileum, ascending and descending colon, and rectum. In rabbit jejunum, ileum, and ascending colon, NHE2 and NHE3 are present in the brush border of epithelial and not goblet cells, again much more in the villus (small intestine)/ surface cells (colon) than the crypt. NHE2 but not NHE3 is present in the brush border of rabbit descending colon surface cells and in small amounts in crypt cells. NHE2 and NHE3 are both human and rabbit small intestinal and colonic epithelial cell brush-border Na+/H+ exchanger isoforms that colocalize in all intestinal segments except rabbit descending colon, which lacks NHE3.

OBJECTIVES: Shift work has been associated with gastrointestinal symptoms such as abdominal pain, constipation, and diarrhea. These symptoms overlap with those reported by patients with functional bowel disorders. Because shift work will lead to misalignment between the endogenous circadian timing system and the external 24 h environment, we hypothesized that nurses participating in shift work will have a higher prevalence of functional bowel disorders when compared with nurses participating in day shifts. METHODS: Nurses engaged in patient care were invited to complete Rome III, irritable bowel syndrome-quality of life measure (IBS-QOL) and modified Sleep-50 questionnaires. Respondents were classified as working day, night, or rotating shifts. The prevalence of IBS, functional constipation, functional diarrhea, and individual gastrointestinal symptoms was determined. RESULTS: Data were available for 399 nurses (214 day shift, 110 night shift, and 75 rotating shift workers). Rotating shift nurses had a significantly higher prevalence of IBS compared to day shift nurses (48% vs. 31%, P<0.01). Multivariable logistic regression correcting for age, gender, and sleep quality proved this association robust. IBS-QOL scores among groups were similar. Prevalence of functional constipation and functional diarrhea was similar between groups. Rotating shift nurses had a significantly higher prevalence of abdominal pain compared to day shift (81% vs. 54%, P<0.0001) and night shift workers (61%, P=0.003). CONCLUSIONS: Participation in shift work, especially rotating shift work, is associated with the development of IBS and abdominal pain that is independent of sleep quality. Circadian rhythm disturbances may have a function in the pathogenesis of IBS and abdominal pain.

The proteinase-activated receptor 2 is expressed on a subset of primary afferent neurons and may participate in the neurogenic component of inflammation. We hypothesized that this receptor may also play a role in neuronal sensitization and contribute to the pathogenesis of pain in inflammatory conditions such as pancreatitis. Using a specific proteinase-activated receptor 2 activating peptide, we found evidence of such sensitization in vitro in the form of enhanced capsaicin- and KCl-evoked release of calcitonin gene-related peptide, a marker for nociceptive signaling. We then demonstrated that injection of the proteinase-activated receptor 2 activating peptide into the pancreatic duct can activate and sensitize pancreas-specific afferent neurons in vivo, as measured by Fos expression in the dorsal horn of the spinal cord. These observations suggest that proteinase-activated receptor 2 contributes to nociceptive signaling and may provide a novel link between inflammation and pain.

OBJECTIVE: Abdominal pain has not been reported generally as a significant feature of the clinical presentation of patients with gastroparesis. METHODS: Using a standardized questionnaire, we analyzed the clinical features of 28 consecutive patients referred with established or suspected gastroparesis over a 4-yr period. The diagnosis of gastroparesis was supported by abnormalities in gastric emptying studies (GES), electrogastrography (EGG), or upper endoscopy (EGD). Diagnostic tests were reviewed. RESULTS: A total of 12 male (mean age 39.5 yr) and 18 female patients (mean age 39.6 yr) were included in this study. These patients had been symptomatic for an average of 37.8 months before their referral to our center. Seven of these patients had insulin-dependent diabetes. Idiopathic gastroparesis was present in more than half of the patients. The symptom profile of the 28 patients was as follows: nausea, 92.9%; abdominal pain, 89.3%; early satiety, 85.7%; and vomiting, 67.9%. The pain was described as burning, vague, or crampy in nature. Only 36% localized to the upper abdomen. In all, 60% of patients complained of postprandial pain, whereas 80% complained of nocturnal pain that interfered with their normal sleeping pattern. In general, pain responded poorly or not at all to prokinetic agents. CONCLUSIONS: Nausea and abdominal pain are the most common complaints of patients with gastroparesis. In 80% of patients, GES and EGG correlated positively.