Ameliorating effects of transcutaneous auricular vagus nerve stimulation on a mouse model of constipation-predominant irritable bowel syndrome.

Limited treatment options have been shown to alter the natural course of constipation-predominant irritable bowel syndrome (IBS-C). Therefore, safer and more effective approaches are urgently needed. We investigated the effects of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of IBS-C. In the current study, C57BL/6 mice were randomly divided into normal control, IBS-C model control, sham-electrostimulation (sham-ES), taVNS, and drug treatment groups. The effects of taVNS on fecal pellet number, fecal water content, and gastrointestinal transit were evaluated in IBS-C model mice. We assessed the effect of taVNS on visceral hypersensitivity using the colorectal distention test. 16S rRNA sequencing was used to analyze the fecal microbiota of the experimental groups. First, we found that taVNS increased fecal pellet number, fecal water content, and gastrointestinal transit in IBS-C model mice compared with the sham-ES group. Second, taVNS significantly decreased the abdominal withdrawal reflex (AWR) score compared with the sham-ES group, thus relieving visceral hyperalgesia. Third, the gut microbiota outcomes showed that taVNS restored Lactobacillus abundance while increasing Bifidobacterium probiotic abundance at the genus level. Notably, taVNS increased the number of c-kit-positive interstitial cells of Cajal (ICC) in the myenteric plexus region in IBS-C mice compared with the sham-ES group. Therefore, our study indicated that taVNS effectively ameliorated IBS-C in the gut microbiota and ICC.

Placebo Response Rates in Acupuncture Therapy Trials for Functional Dyspepsia: A Systematic Review and Meta-Analysis.

BACKGROUND: Functional dyspepsia (FD) is a functional digestive disease with limited management selection. Previous studies revealed that acupuncture therapy is effective for FD. However, because sham controls were not implemented in most clinical trials following acupuncture therapy, it is difficult to differentiate overall treatment responses from placebo. This study aims to quantify placebo responses in clinical trials in which FD patients received sham manual acupuncture (MA) and sham electroacupuncture (EA). MATERIALS AND METHODS: Randomized controlled trials of MA and EA for FD patients were searched in PubMed, Web of Science, Cochrane Library, and Embase databases, as well as 4 Chinese language databases from inception to January 2021. RevMan 5.20 software was used for pooled analysis of symptom scores and quality of life. The symptom scores were combined using standard mean difference (SMD) or weighted mean difference (WMD) with a 95% confidence interval (CI). The quality of included studies was tested using modified Jadad scale and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist. Egger's test, Begg's test, and sensitivity analyses were conducted using Stata 11.0 statistical software. The protocol of this study is registered in PROSPERO as CRD42021233858. RESULTS: After screening, the current systematic review included 13 randomized controlled trials, of which 8 studies were used in the meta-analysis. Regarding subjective outcomes, the combined effect of sham MA on FD symptoms was [SMD=-0.42, 95% CI (-0.72, -0.12); P=0.005], whereas sham EA treatment was [SMD=-0.54, 95% CI (-0.81, -0.27); P<0.001]. The combined effect on FD quality of life of post-sham MA group was [SMD=-0.32, 95% CI (-0.52, -0.12); P=0.002]. With regard to objective outcomes, the combined effect of sham EA on dominant frequency was [WMD=-0.11, 95% CI (-0.30, -0.08); P=0.24], while the combined effect of sham EA on dominant power was [WMD=-3.35, 95% CI (-8.04, 1.35); P=0.16]. CONCLUSIONS: Sham MA and sham EA remarkably improve symptoms and quality of life scores of FD without influencing objective outcomes, highlighting the significance of sham controls in acupuncture therapy clinical trials.

Ameliorating Effects of Transcutaneous Electrical Acustimulation at Neiguan (PC6) and Zusanli (ST36) Acupoints Combined with Adaptive Biofeedback Training on Functional Outlet Obstruction Constipation.

BACKGROUND: Stimulant laxatives are still considered the most common treatment for functional outlet obstruction constipation (FOOC). However, the effectiveness of laxatives is unsatisfactory, and the long-term use of laxatives may cause certain adverse events. With this in mind, it is, however, paramount that novel complementary treatment(s) and/or other forms of alternative medicine are adequately investigated. AIMS: The study aims to explore the effects and potential mechanism(s) of transcutaneous electrical acustimulation (TEA) combined with adaptive biofeedback training (ABT) on FOOC. METHODS: A total of forty-five patients with FOOC were recruited and were randomly assigned to receive either Macrogol 4000 Powder (MAC, 10 g bid) (group A, n = 15) only, ABT + MAC + Sham-TEA (group B, n = 15), or TEA + ABT + MAC (group C, n = 15) in a six-week study. Individual patients' constipation-symptoms (PAC-SYM) and constipation-quality of life (PAC-QOL) were both assessed and scored. Serum acetylcholine (Ach) and nitric oxide (NO) were measured from drawn blood samples while individual patients' heart rate variability (HRV) was calculated at baseline and after each corresponding therapy. Anorectal manometry and balloon expulsion test were both performed before and after treatment. RESULTS: Firstly, participants in group C had significantly lower scores of PAC-SYM, PAC-QOL, and a decreased anal defecating pressure (ADP) as compared to participants in group B (all p < 0.050). These results, however, suggest the TEAs effect. Secondly, the low-frequency band (LF)/(LF + HF) ratio in groups B and C were decreased as compared to group A (p=0.037, p=0.010, respectively) regarding HRV. On the other hand, the high-frequency band (HF)/(LF + HF) ratio in groups B and C showed an opposite outcome. Finally, the serum Ach in groups B and C was significantly higher as compared to group A (p=0.023, p=0.012, respectively). Of significant importance, the serum NO in groups B and C were notably low as compared to group A (p=0.001, p < 0.001, respectively). CONCLUSIONS: TEA, combined with ABT, effectively improves constipation symptoms as well as QOL in FOOC patients. It is, however, achieved by decreasing ADP, which mechanisms are mediated via the autonomic and enteric mechanisms.