Abdominal Massage Reduces Visceral Hypersensitivity via Regulating GDNF and PI3K/AKT Signal Pathway in a Rat Model of Irritable Bowel Syndrome

Abstract

Changes in gut motility and visceral hypersensitivity are two major features of irritable bowel syndrome (IBS). Current drug treatments are often poorly efficacious, with many side effects for patients with IBS. Complementary therapies, such as acupuncture or abdominal massage, have received more attention in recent years. In this study, a rat model of IBS with diarrhea (IBS-D) was established by instillation of acetic acid from the colon. The effects of abdominal massage on changes in gut motility, visceral hypersensitivity, and the possible mechanism were investigated. Continuous abdominal massage could decrease the stool consistency score and increase the efflux time of glass beads compared with model groups, while also decreasing mast cell counts in IBS-D rats. The mRNA and protein expressions of neuronal nitric oxide synthase (nNOS), choline acetyl transferase (CHAT), and protein gene product 9.5 (PGP9.5) were significantly upregulated by continuous abdominal massage compared with model groups. Continuous abdominal massage also improved the ultrastructure of enteric glial cells (EGCs) by decreasing the number of mitochondria and increasing the level of the heterochromatin. Meanwhile, continuous abdominal massage could upregulate the expression of glial cell line-derived neurotrophic factor (GDNF) and P-Akt/Akt. Furthermore, it could reduce visceral hypersensitivity and improve the IBS-D symptoms by regulating the phosphoinositide 3-kinase (PI3K)-Akt pathway, which would provide a novel method for the treatment of IBS-D in the clinical setting.

Study on the Effective Material Basis and Mechanism of Traditional Chinese Medicine Prescription (QJC) Against Stress Diarrhea in Mice

“…Current studies have shown that anti-TNF drugs can be used to exert anti-inflammatory effects, thereby effectively treating inflammatory bowel disease ( 35 , 36 ); however, few studies have proven that drugs act directly through TNF signaling pathways. Conversely, the PI3K–Akt signaling pathway is directly related to stress-induced UC and irritable bowel syndrome (IBS) ( 37 , 38 ). The PI3K–Akt signaling pathway is reportedly related to various diverse physiological stresses.…”

“…The PI3K–Akt signaling pathway is reportedly related to various diverse physiological stresses. It plays a crucial regulatory role during cellular stress ( 39 – 41 ) and is reportedly associated with stress-induced diarrhea, predominantly IBS (IBS-D), and UC ( 38 , 42 – 44 ). In addition, the results of KEGG enrichment analysis show that the PI3K–Akt signaling pathway (number of enriched genes = 39) can enrich more genes than the TNF signaling pathway (number of enriched genes = 23).…”

“…The PTEN expression was increased significantly under the induction of serotonin hydrochloride, but after QJC administration, the expression decreased; this is speculated to be caused by the normalization of phosphorylation of PI3K and Akt after QJC administration. Studies have shown that the expression of Akt was significantly decreased in mice with IBS ( 38 ). Interestingly, the active ingredients quercetin, luteolin, and kaempferol of QJC may also act as selective aryl hydrocarbon receptor (AHR) modulators in the AHR signaling and trigger an anti-stress diarrhea effect ( 52 ).…”

Electroacupuncture Alleviates Visceral Hypersensitivity in IBS-D Rats by Inhibiting EGCs Activity through Regulating BDNF/TrkB Signaling Pathway

“…Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder with persistent or recurrent episodes of intestinal disorder [ 1 ]. It is characterized by abdominal pain, abdominal distension, altered bowel habits, and/or character of stool that severely affect the quality of patients' life [ 2 ]. A wide spectrum of clinical manifestations and a lack of a specific diagnostic basis [ 2 ] make it difficult to treat.…”

“…It is characterized by abdominal pain, abdominal distension, altered bowel habits, and/or character of stool that severely affect the quality of patients' life [ 2 ]. A wide spectrum of clinical manifestations and a lack of a specific diagnostic basis [ 2 ] make it difficult to treat. Although medication, nutritional support, and psychotherapy are currently in use, few drugs are available for effective treatment [ 3 ].…”