Altered behavior and digestive outcomes in adult male rats primed with minimal colon pain as neonates

<p>Abstract</p> <p>Background</p> <p>Neonatal colon irritation (CI; pain or inflammation) given for 2 weeks prior to postnatal day 22 (PND22), causes long-lasting functional disorders in rats that can be seen 6 months after the initial insult. This study looked at the effect of varying the frequency and duration of neonatal CI on the rate of growth, digestive outcomes, exploratory activity, and colon and skin sensitivity in adult rats.</p> <p>Methods</p> <p>Male Sprague-Dawley rats were given CI using repeated colorectal distension (CRD) at different time intervals and for varying durations starting at PND 8, 10 or 14. Control rats were handled by the investigator without any intracolonic insertion. Further experiments were done on adult rats. Digestive outcomes (food and water consumption, fecal and urinary outputs) were measured using metabolic cages. Exploratory behavior was measured using digital video tracking in an open field. Cutaneous sensitivity was assessed by measuring the responses to mechanical and heat stimuli applied to the shaved abdomen or hind paws. Visceral sensitivity was measured by recording electromyographic responses, under light isoflurane anesthesia, from the external oblique muscles in response to CRD.</p> <p>Results</p> <p>No significant weight differences were observed between CI and control rats. Exploratory behavior was reduced in rats with neonatal CI compared to control. Digestive outputs and somatic and visceral sensitivity changed between different treatment groups with earlier and more frequent insults yielding a higher deviation from normal.</p> <p>Conclusion</p> <p>The diversity of behavioral and digestive symptoms in these rats parallels the diversity of symptoms in patients with functional gastrointestinal disorders and is consistent with global plastic changes affecting more than one system in the organism.</p

Supplemental Information 4: Multicolor FACS analyses of cultured DC cells

This study investigated the mechanism of protein disulfide-isomerase A3 (PDIA3)-induced visceral hypersensitivity in irritable bowel syndrome (IBS). Rats were treated with saline (control), acetic acid and restraint stress (IBS model), empty vector (RNAi control) and PDIA3-RNAi vector (PDIA3-RNAi). Mesenteric lymph node DCs (MLNDCs) and splenic CD4+/CD8+ T cells were isolated for co-cultivation. Compared with control, MLNDCs co-cultured with CD4+ or CD8+ T cells showed an increased ability to promote T cell proliferation and produced more IL-4 or IL-9 secretion. Compared with the RNAi control, MLNDCs from the PDIA3 knockdown models were less effective in promoting the proliferation of CD4+/CD8+ T cells. It is concluded that PDIA3 plays an important role in the development of IBS through the DC-mediated activation of T cells, resulting in degranulation of MCs and visceral hypersensitivity

Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65998/1/jphysiol.2005.096073.pd

Analysis of the effect of locally applied inhomogeneous static magnetic field-exposure on mouse ear edema - a double blind study

The effect static magnetic field (SMF)-exposure may exert on edema development has been investigated. A 6 h long whole-body (WBSMF) or local (LSMF), continuous, inhomogeneous SMF-exposure was applied on anesthetized mice in an in vivo model of mustard oil (MO)-induced ear edema. LSMF was applied below the treated ear, below the lumbar spine, or below the mandible. Ear thickness (v) was checked 8 times during the exposure period (at 0, 0.25, 1, 2, 3, 4, 5, and 6 h). The effect size of the applied treatment (eta) on ear thickness was calculated by the formula eta = 100% x (1-vj/vi), where group i is the control group and j is the treated group. Results showed that MO treatment in itself induced a significant ear edema with an effect of 9% (p11% in both cases compared to SMF-exposure alone (p<0.001). In these cases SMF-exposure alone without MO treatment reduced ear thickness significantly (p<0.05), but within estimated experimental error. In cases of LSMF-exposure on the head, a significant SMF-exposure induced ear thickness reduction was found (eta = 5%, p<0.05). LSMF-exposure on the spine affected ear thickness with and without MO treatment almost identically, which provides evidence that the place of local SMF action may be in the lower spinal region

Transient Gastric Irritation in the Neonatal Rats Leads to Changes in Hypothalamic CRF Expression, Depression- and Anxiety-Like Behavior as Adults

A disturbance of the brain-gut axis is a prominent feature in functional bowel disorders (such as irritable bowel syndrome and functional dyspepsia) and psychological abnormalities are often implicated in their pathogenesis. We hypothesized that psychological morbidity in these conditions may result from gastrointestinal problems, rather than causing them.Functional dyspepsia was induced by neonatal gastric irritation in male rats. 10-day old male Sprague-Dawley rats received 0.1% iodoacetamide (IA) or vehicle by oral gavage for 6 days. At 8-10 weeks of age, rats were tested with sucrose preference and forced-swimming tests to examine depression-like behavior. Elevated plus maze, open field and light-dark box tests were used to test anxiety-like behaviors. ACTH and corticosterone responses to a minor stressor, saline injection, and hypothalamic CRF expression were also measured.Behavioral tests revealed changes of anxiety- and depression-like behaviors in IA-treated, but not control rats. As compared with controls, hypothalamic and amygdaloid CRF immunoreactivity, basal levels of plasma corticosterone and stress-induced ACTH were significantly higher in IA-treated rats. Gastric sensory ablation with resiniferatoxin had no effect on behaviors but treatment with CRF type 1 receptor antagonist, antalarmin, reversed the depression-like behavior in IA-treated ratsThe present results suggest that transient gastric irritation in the neonatal period can induce a long lasting increase in depression- and anxiety-like behaviors, increased expression of CRF in the hypothalamus, and an increased sensitivity of HPA axis to stress. The depression-like behavior may be mediated by the CRF1 receptor. These findings have significant implications for the pathogenesis of psychological co-morbidity in patients with functional bowel disorders