Transitional changes in gastrointestinal transit and rectal sensitivity from active to recovery of inflammation in a rodent model of colitis

Patients with ulcerative colitis are typically suspected of an inflammatory flare based on suggestive symptoms of inflammation. The aim of this study was to evaluate the impact of inflammation on colonic motility and rectal sensitivity from active to recovery of inflammation. Male rats were given drinking water with 5% dextran sulfate sodium for 7 days. Inflammation, intestinal motor and sensory functions were investigated weekly for 6 weeks. (1) The disease activity index score, fecal calprotectin and tumor necrosis factor alpha were increased from Day 0 to Day 7 (active inflammation) and then decreased gradually until recovery. (2) Distal colon transit was accelerated on Day 7, and then remained unchanged. Whole gut transit was delayed on Day 7 but accelerated from Day 14 to Day 42. (3) Rectal compliance was unaffected from Day 0 to Day 7, but decreased afterwards. (4) Rectal hypersensitivity was noted on Day 7 and persistent. (5) Plasma acetylcholine was decreased on Day 7 but increased from Day 14 to Day 42. Nerve growth factor was increased from Day 7 to Day 42. DSS-induced inflammation leads to visceral hypersensitivity that is sustained until the resolution of inflammation, probably mediated by NGF. Rectal compliance is reduced one week after the DSS-induced inflammation and the reduction is sustained until the resolution of inflammation. Gastrointestinal transit is also altered during and after active colonic inflammation.

Simulated stool for assessment of anorectal physiology

Fecal continence is maintained by several mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, mobility, and psychological factors. The homeostatic balance is easily disturbed, resulting in symptoms including fecal incontinence and constipation. Current technologies for assessment of anorectal function have limitations. Overlap exist between data obtained in different patient groups, and there is lack of correlation between measurements and symptoms. This review describes a novel technology named Fecobionics for assessment of anorectal physiology. Fecobionics is a simulated stool, capable of dynamic measurements of a variety of variables during defecation in a single examination. The data facilitate novel analysis of defecatory function as well as providing the foundation for modeling studies of anorectal behavior. The advanced analysis can enhance our physiological understanding of defecation and future interdisciplinary research for unraveling defecatory function, anorectal sensory-motor disorders, and symptoms. This is a step in the direction of improved diagnosis of anorectal diseases.

Sacral nerve stimulation with appropriate parameters improves constipation in rats by enhancing colon motility mediated via the autonomic-cholinergic mechanisms

Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, its effects are limited, and mechanisms are largely unknown. We investigated the effects and mechanism of SNS with appropriate parameters on constipation in rats treated with loperamide. First, using rectal compliance as an outcome measure, an experiment was performed to derive effective SNS parameters. Then, a 7-day SNS was performed in rats with constipation induced by loperamide. Autonomic functions were assessed by spectral analysis of heart rate variability (HRV) derived from an electrocardiogram. Serum levels of pancreatic polypeptide (PP), norepinephrine (NE), and acetylcholine (ACh) in colon were assessed. 1) Acute SNS at 5 Hz, 100 µs was found effective in enhancing rectal compliance and accelerating distal colon transit ( P < 0.05 vs. sham SNS). 2) The 7-day SNS normalized loperamide-induced constipation, assessed by the number, weight, and water content of fecal pellets, and accelerated the distal colon transit (29.4 ± 3.7 min with sham SNS vs. 16.4 ± 5.3 min with SNS but not gastric emptying or intestinal transit. 3) SNS significantly increased vagal activity ( P = 0.035) and decreased sympathetic activity ( P = 0.012), assessed by spectral analysis of HRV as well as by the serum PP. 4) SNS increased ACh in the colon tissue; atropine blocked the accelerative effect of SNS on distal colon transit. We concluded that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility, mediated via the autonomic-cholinergic function. NEW & NOTEWORTHY Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, effects are limited, and mechanisms are largely unknown. This paper shows that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility mediated via the autonomic-cholinergic function.

Theoretical Tools to Analyze Anorectal Mechanophysiological Data Generated by the Fecobionics Device

A mechanical approach is needed for understanding anorectal function and defecation. Fecal continence is achieved by several interacting mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, motility, and psychological factors. The balance is easily disturbed, resulting in symptoms such as fecal incontinence and constipation. Novel technologies have been developed in recent years for studying anorectal function. Especially, the Fecobionics device, a simulated feces, has gained attention recently. This facilitates new analysis of anorectal mechanical function. In this study, a theoretical model is developed to analyze anorectal mechanophysiological data generated by the Fecobionics device. Theoretical approaches can enhance future interdisciplinary research for unraveling defecatory function, sensory-motor disorders, and symptoms. This is a step in the direction of personalized treatment for gastrointestinal disorders based on optimized subtyping of anorectal disorders.