Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul 5;11(2):115-127.
doi: 10.2478/jtim-2023-0086. eCollection 2023 Jul.

Therapeutic potential and mechanisms of sacral nerve stimulation for gastrointestinal diseases

Ximeng Wang  1 , Jiande Dz Chen  2
Affiliations

Therapeutic potential and mechanisms of sacral nerve stimulation for gastrointestinal diseases

Ximeng Wang et al. J Transl Int Med. .

Abstract

Background: The aim of this systemtic review is to introduce clinical applications (especially emerging) and potential mechanisms of sacral nerve stimulation (SNS) for treating various gastrointestinal diseases.

Materials and methods: PubMed and Web of Science were searched for studies published on SNS and its clinical applications in fecal incontinence (limited to systematic review and meta-analysis of clinical studies), constipation (limited to reviews and randomized control clinical studies), irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and upper gastrointestinal motility disorders. The relevant studies were pooled, and their findings were summarized and discussed.

Results: SNS is an approved method for treating fecal incontinence. Systematic review and meta-analysis demonstrated high efficacy of the SNS therapy for fecal incontinence. Increased anal sphincter pressure and improvement in rectal sensation were reported as major mechanisms involved in the SNS therapy. SNS has also been proposed for treating constipation, but the therapy has been shown ineffective. There is a lack in SNS methodological optimization and mechanistic research. A few basic and clinical studies have reported the potential of SNS for treating visceral pain in IBS. SNS seemed capable of improving mucosal barrier functions. Several case reports are available in the literature on the treatment of IBD with SNS. Several laboratory studies suggested therapeutic potential of a special method of SNS for IBD. Cholinergic anti-inflammatory mechanisms were reported. Due to a recently reported spinal afferent and vagal efferent pathway of SNS, a few preclinical studies reported the potential of SNS for upper gastrointestinal motility disorders. However, no clinical studies have been performed.

Conclusions: SNS for fecal incontinence is a well-established clinical therapy. However, the current method of SNS is ineffective for treating constipation. Further methodological development and randomized clinical trials are needed to explore potential applications of SNS for IBS and IBD.

Keywords: autonomic functions; functional gastrointestinal diseases; inflammatory bowel disease; sacral nerve stimulation; sacral neuromodulation.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Jiande DZ Chen is an Editorial Board Member of the journal. The article was subject to the journal’s standard procedures, with peer review handled independently of the editor and the affiliated research groups.

Figures

Figure 1
Figure 1
Innervation of the pelvic organs. The parasympathetic nervous system includes vagus nerve and sacral nerve. The vagus nerve innervates peripheral organs in the proximal part of the body, such as heart, lung, liver, stomach and small intestine, whereas the sacral nerve innervates pelvic organs such as rectum, anus, vagina and bladder via the pelvic nerve. This direct innervation provides opportunities for the use of sacral nerve stimulation for treating disorders of these organs. Reproduced from Jobling et al., 2014[1]. DRG: dorsal root ganglion.
Figure 2
Figure 2
Sacral nerve stimulation for fecal incontinence. Left: embodiment of the stimulation lead and pulse generator; top right: Implantable pulse generator connected with stimulation lead from Medtronic Inc; bottom right: continuous stimulation pulses used for treating fecal incontinence.
Figure 3
Figure 3
Effects of SNS with optimized parameters and different daily stimulation durations on colonic myeloperoxidase (MPO) activity in normal (control) and TNBS (2,4,6-trinitrobenzene sulfonic acid)-treated rats. Sham-SNS: no stimulation; 0.5 h-SNS: daily 0.5 h SNS. SNS: sacral nerve stimulation.
Figure 4
Figure 4
Effects of SNS on colon length rats. Control: regular rats without any treatment; sham-SNS: rats treated with TNBS and implanted with SNS electrodes without stimulation; 0.5/1/3-hour SNS: rats treated with TNBS and 0.5/1/3 hour daily SNS for a week; appearance of the colon at the end of the 7-day treatment. Modified from Zhang et al.[11] SNS: sacral nerve stimulation; TNBS: 2,4,6-trinitrobenzene sulfonic acid.
Figure 5
Figure 5
Effects of SNS on multiple inflammatory cytokines. top-left: Tumor necrosis factor-α (TNF-α) in colon tissues in various groups of rats: NML: normal rats without treatment, TNBS: rats treated with TNBS but not SNS; SNS: rats treated with TNBS and then SNS of optimized parameters; SNS-N: rats treated with TNBS and then SNS of parameters used for fecal incontinence; top-right: interleukin-10 (IL-10) in colon tissues; bottom-left: IL-13 in colon tissues; bottom-right: IL-5 in colon tissues. *P < 0.05, vs. NML; #P < 0.05, vs. TNBS; &P < 0.05 vs. SNS. Modified from Zhang et al.[11] SNS: sacral nerve stimulation; TNBS: 2,4,6-trinitrobenzene sulfonic acid.
Figure 6
Figure 6
Neural pathways involved in the anti-inflammatory effect of SNS. SNS activates neurons in the nucleus tractus solitarius, resulting in an enhanced vagal efferent activity; acetylcholine (ACH) is released in the colon due to activation of vagal efferent nerve; ACH acts on a special receptor in macrophage to balance inflammatory cytokine release. SNS also acts on the colon via pelvic splanchnic nerve. SNS: sacral nerve stimulation.
Figure 7
Figure 7
Gastric slow waves recorded from a dog via chronically implanted electrodes on the gastric serosa. Top channel: corpus; bottom channel: distal antrum. Left: normal slow waves with a regular frequency (about 5 waves/min), propagating from the corpus to the distal antrum. Right: Abnormal slow waves with a normal pacemaker in the corpus (top channel) and an ectopic pacemaker firing at a higher frequency in the distal antrum. Reproduced from[83].
Figure 8
Figure 8
Effects of SNS on gastric and small intestinal slow waves impaired by the treatment of glucagon. A. Percentages of normal gastric slow waves for baseline, glucagon, glucagon + 5 Hz SNS, and glucagon + 25 Hz SNS. B. Percentages of normal intestinal slow waves for baseline, glucagon, glucagon + 5 Hz SNS, and glucagon + 25 Hz SNS. *P < 0.05 vs. baseline. &P < 0.05 vs. glucagon. Reproduced from Wang et al..[16] SNS: sacral nerve stimulation.
See this image and copyright information in PMC

References

    1. Jobling P, K O'Hara, Hua S. Female reproductive tract pain: targets, challenges, and outcomes. Front Pharmacol. 2014;5:17. - PMC - PubMed
    1. Lee JC, Cheng CH, Yen CT. Morphological study of myelinated and unmyelinated fibres in the sacrococcygeal dorsal roots of the rat. Folia Morphol (Warsz) 2019;78:267. –. - PubMed
    1. Schalow G. Ventral root afferent and dorsal root efferent fibres in dog and human lower sacral nerve roots. Gen Physiol Biophys. 1992;11:123. –. - PubMed
    1. Stewart WF Van Rooyen JB Cundiff GW Abrams P Herzog AR Corey R et alPrevalence and burden of overactive bladder in the United States World J Urol 200320327.– - PubMed
    1. Sukhu T, MJ Kennelly,, R Kurpad. Sacral neuromodulation in overactive bladder: a review and current perspectives. Res Rep Urol. 2016;8:193. –. - PMC - PubMed

LinkOut - more resources