Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway

Abstract

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450–500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway. NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.

Ameliorating effects and mechanisms of transcutaneous auricular vagal nerve stimulation on abdominal pain and constipation

“…We speculated that this might be attributed to (a) possible innervation of the vagus nerve to the rectum and/or (b) a possible vagal afferent and sacral efferent pathway. In a few recent studies, sacral nerve stimulation was reported to alter functions of the gastrointestinal organs (stomach and small intestine) that are not innervated with the sacral nerve ( 77 , 78 ), and a spinal afferent and vagal efferent pathway was indicated with the sacral nerve stimulation ( 79 ).…”

Bioelectronic medicine for restoring autonomic balance in autoimmune diseases

“…Since the vagus and sacral nerves contain both the afferent and efferent parasympathetic fibers, the antiinflammatory effect of VNS and SNS could be due to either a direct activation of these parasympathetic efferents and/or the activation of the parasympathetic afferents projecting to the brainstem parasympathetic control centers and resulting in activation of the vagal and sacral efferents. [96,97] Moreover, the vagosympathetic reflex has been proposed, where the abdominal vagal efferents in the celiac ganglion activate the sympathetic efferents in the greater splanchnic nerve, including the splenic nerve [98][99][100][101][102][103] and adrenal nerve. [104] With that rationale, Galvani Bioelectronics recently initiated clinical trials in the US and UK, where a direct splenic nerve stimulation (rather than VNS) is being used to treat the RA.…”

Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients

“…Recently, SNM has been shown to reduce intestinal inflammation in rodent models of inflammatory bowel diseases, suppress a number of proinflammatory cytokines including TNF, and enhance anti-inflammatory cytokines such as IL-10 in both intestinal tissues and in circulation ( 55 , 56 ). The anti-inflammatory effect of SNM on the colon is mediated via the spinal afferent and vagal efferent pathways evidenced by the following factors ( 57 ): (1) SNM activates neurons in the nucleus tractus solitaries ( 57 , 58 ); (2) SNM increases vagal efferent activity as assessed by the spectral analysis of heart rate variability and plasma level of pancreatic polypeptide ( 55 ); (3) bilateral subdiaphragmatic vagotomy almost completely abolishes the anti-inflammatory effect of SNM on the colon ( 57 ); and (4) SNM induces the release of acetylcholine in the colon ( 55 ). These findings suggest that SNM shares a similar vagal efferent pathway as VNS.…”