Peripheral non-invasive focused ultrasound alleviates constipation by reducing gastrointestinal inflammation.

Abstract

Constipation affects approximately 20% of the US population, with diverse treatment options available due to the unclear onset and causes of the condition. Recently, focused ultrasound (FUS) has been proposed as a novel, non-invasive peripheral neuromodulatory treatment that may reduce this inflammation. We utilized a loperamide-induced constipation rat model, which is a widely used model to study constipation and potential therapeutic interventions. This study investigated the effects of FUS treatment on colonic inflammation and motility. We report that loperamide treatment did not alter colon morphology, but upregulated interleukin (IL)-6, IL-10, IL-1ra and several other cytokines. FUS treatment notably reduced the expression of IL-2, IL-4, IL-17 and other markers of inflammation. Additionally, FUS therapy also reduced the expression of chemokines, such as CXC3CL-1 and CXCL-7, and acute phase proteins, including vascular endothelial growth factor and intercellular adhesion molecule 1 in loperamide-FUS-treated rats. One week post-treatment, cytokine and chemokine profiles showed a sustained decrease of inflammation in the distal colon, with FUS treatment continuing to reduce several inflammatory mediators. These results demonstrate non-invasive FUS markedly reduced the expression of pro-inflammatory cytokines, chemokines and acute phase proteins in both the proximal and distal colon of loperamide-treated rats and can plausibly serve as a therapeutic for chronic constipation and other inflammatory gastrointestinal disorders.