Sacral nerve stimulation improves colonic inflammation mediated by autonomic‐inflammatory cytokine mechanism in rats

Abstract

Background Vagal nerve stimulation (VNS) was reported to have a therapeutic potential for inflammatory bowel disease (IBD). This study was designed to determine effects and mechanisms of SNS on colonic inflammation of in rodent models of IBD and compare the difference among SNS, VNS, and SNS plus VNS. Methods Intestinal inflammation in rats was induced by intrarectal administration of TNBS (2,4,6‐Trinitrobenzenesulfonic acid) on the first day. Five days after intrarectal TNBS, the rats were treated with sham‐VNS, VNS, Sham‐SNS, SNS, and SNS + VNS for 10 days. In another experiment, after 10 days of 4% DSS (dextran sodium sulfate) in drinking water, rats were treated with 10‐day sham‐SNS and SNS. Various inflammatory responses were assessed; mechanisms involving autonomic functions and inflammatory cytokines were investigated. Key Results (a) VNS, SNS, and VNS + SNS significantly and equally decreased the disease activity index and macroscopic scores, and normalized colon length; (b) IL‐10 was decreased by TNBS but increased with SNS, VNS, and SNS + VNS; pro‐inflammatory cytokines, IL‐6, IL‐17A, MCP‐1 and TNF‐α, were increased by TNBS but decreased with SNS, VNS, and SNS + VNS (P < .05); MPO activity was decreased by SNS, VNS, and SNS + VNS; (c) SNS, VNS, and SNS + VNS remarkably increased vagal activity that was suppressed by TNBS (P < .05); (d) smilar SNS effects were noted in rats with DSS‐induced colitis. Conclusions & Inferences SNS presents similar anti‐inflammatory effects as VNS by inhibiting pro‐inflammatory cytokines and increasing anti‐inflammatory cytokines via the autonomic pathway. Similar to VNS, SNS may also have a therapeutic potential for colonic inflammation.

An intravital window to image the colon in real time

“…Such in vivo data will be essential for modeling the ENS in silico 79 . The window allows for unique insight into the effect of peripheral neuromodulation, as vagal and sacral nerve stimulation have therapeutic effects on gastrointestinal motility and inflammation 30,[81][82][83] .…”

Neuronal regulation of the gut immune system and neuromodulation for treating inflammatory bowel disease

“…41 Moreover, stimulation of the vagus exerts anti-inflammatory effects in animal models [42][43][44] and in humans. 7,45 Inflammation in the distal gut can be suppressed by stimulation of the pelvic nerves 46 and inflammation is also reduced by stimulation of sympathetic nerves 47 or by activation of enteric nerve pathways. 35 Vagal nerve stimulation can contribute to reduction of inflammation in the gut in at least three ways: by stimulating afferent neurons that signal to the brain to activate efferent pathways, that may include sympathetic outputs from the central nervous system; 47 by activating vagal efferent pathways; and by stimulating vagal afferents to release transmitters from their peripheral ends (Fig.…”

The rise of bioelectric medicine sparks interest among researchers, patients, and industry

“…The National Institutes of Health (NIH) and the Defense Advanced Research Projects Agency (DARPA) have also invested significantly in the field through programs such as Stimulating Peripheral Activity to Relieve Conditions, or SPARC (14), and Electrical Prescriptions, or ElectRx. One recent study funded by DARPA's ElectRx, for example, found that sacral nerve stimulation decreased inflammation in the colon (15). Market intelligence firms predict the bioelectronic device market will reach between $16 and $60 billion annually within the next 5 to 10 years (16,17).…”