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1.
Neuromodulation ; 27(2): 382-391, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38127047

RESUMEN

OBJECTIVES: Nearly half of patients with slow transit constipation (STC) are not completely satisfied with their traditional remedies. We aimed to evaluate the therapeutic value and possible involved mechanism of transcutaneous electrical acustimulation (TEA) at ST36 in patients with STC. MATERIALS AND METHODS: Seventy patients with STC were randomly divided into TEA (n = 35) and sham-TEA (n = 35) to undergo a two-week treatment with TEA at ST36 or sham point. After the two-week treatment, 18 patients from each group randomly underwent a few physiological tests, including the electrocardiogram (ECG), anorectal manometry, colon transit test, and blood drawing. After a two-week washout period, TEA was performed in both groups for two weeks. RESULTS: Spontaneous bowel movements per week were increased, and scores of constipation symptoms were decreased, after a two-week blind TEA but not sham-TEA, which were sustained after a two-week washout period. Improvement in quality of life and psychologic states also was observed with blind TEA treatment. Mechanistically, the two-week blind TEA accelerated colon transit assessed by barium strip excretion rate (the effect was sustained after a two-week washout period), enhanced vagal nerve activity evaluated by the spectral analysis of heart rate variability derived from the ECG, and decreased circulating vasoactive intestinal peptide. CONCLUSIONS: Noninvasive TEA relieves constipation and improves quality of life and psychologic states in patients with STC, and the effects are sustained for ≥two weeks. The therapeutic effects of TEA may be attributed to the acceleration of colon transit and decrease of vasoactive intestinal peptide mediated through the vagal mechanism.


Asunto(s)
Calidad de Vida , Estimulación Eléctrica Transcutánea del Nervio , Humanos , Péptido Intestinal Vasoactivo , Tránsito Gastrointestinal/fisiología , Estreñimiento/terapia , Colon
2.
Bioelectron Med ; 9(1): 27, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37990288

RESUMEN

Gastrointestinal (GI) disorders, which extend from the esophagus to the anus, are the most common diseases of the GI tract. Among these disorders, pain, encompassing both abdominal and visceral pain, is a predominant feature, affecting the patients' quality of life and imposing a substantial financial burden on society. Pain signals originating from the gut intricately shape brain dynamics. In response, the brain sends appropriate descending signals to respond to pain through neuronal inhibition. However, due to the heterogeneous nature of the disease and its limited pathophysiological understanding, treatment options are minimal and often controversial. Consequently, many patients with GI disorders use complementary and alternative therapies such as neuromodulation to treat visceral pain. Neuromodulation intervenes in the central, peripheral, or autonomic nervous system by alternating or modulating nerve activity using electrical, electromagnetic, chemical, or optogenetic methodologies. Here, we review a few emerging noninvasive neuromodulation approaches with promising potential for alleviating pain associated with functional dyspepsia, gastroparesis, irritable bowel syndrome, inflammatory bowel disease, and non-cardiac chest pain. Moreover, we address critical aspects, including the efficacy, safety, and feasibility of these noninvasive neuromodulation methods, elucidate their mechanisms of action, and outline future research directions. In conclusion, the emerging field of noninvasive neuromodulation appears as a viable alternative therapeutic avenue for effectively managing visceral pain in GI disorders.

3.
Dig Dis Sci ; 68(1): 98-105, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35503488

RESUMEN

BACKGROUND: Due to complex pathophysiology of functional dyspepsia, medications to treat functional dyspepsia are not effective for all patients. Transcutaneous electrical acustimulation (TEA) is an potentially effective therapy for functional dyspepsia without proofs of definite mechanisms. AIMS: We aimed to investigate the therapeutic impacts of TEA on postprandial distress syndrome (PDS) and explore potential neuroimmune mechanisms. METHODS: We conducted a double-blinded, randomized, controlled trial in 30 PDS patients randomized for 4-week TEA or sham-TEA. Dyspeptic symptoms, gastric accommodation, gastric emptying and heart rate variability (HRV) were assessed. Duodenal mucosal inflammation was also evaluated. RESULTS: The dyspeptic symptoms were improved with TEA compared with sham-TEA (P = 0.03). The initial satiety volume and the maximum tolerable volume (MTV) were both improved after the TEA treatment, compared with the sham-TEA group (P all < 0.05). The gastric emptying time (T1/2) was not altered with TEA or sham-TEA. The TEA treatment increased vagal activity and decreased sympathovagal ratio assessed by HRV (P all < 0.01). The IL-6 expression in bulb mucosa was downregulated by the TEA treatment compared to the baseline (P < 0.05). CONCLUSIONS: Noninvasive TEA improves gastric accommodation and dyspeptic symptoms, possibly by downregulating the IL-6 expression in duodenal bulb mucosa via the vagal efferent pathway.


Asunto(s)
Dispepsia , Electroacupuntura , Gastropatías , Humanos , Dispepsia/terapia , Interleucina-6 , Vaciamiento Gástrico
4.
Neuromodulation ; 26(8): 1851-1857, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35597733

RESUMEN

BACKGROUND/AIMS: Stress is known to inhibit gastric motility. The aim of this study was to investigate the effects and autonomic mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) on cold stress (CS)-induced impairment in gastric motility that are relevant to the brain-gut interactions in healthy volunteers. MATERIALS AND METHODS: Healthy volunteers (eight women; age 28.2 ± 1.8 years) were studied in four randomized sessions (control, CS, CS + taVNS, and CS + sham-electrical stimulation [sham-ES]). Each session was composed of 30 minutes in the fasting state and 30 minutes after a standard test meal. CS was induced during minutes 10 to 30 after the meal, whereas taVNS or sham-ES was performed during minutes 0 to 30 after the meal. The electrogastrogram and electrocardiogram were recorded for assessing gastric slow waves and autonomic functions, respectively. RESULTS: First, CS decreased the percentage of normal gastric slow waves (59.7% ± 9.8% vs 85.4% ± 4.5%, p < 0.001 vs control); this impairment was dramatically improved by taVNS (75.5% ± 6.3% vs 58.4% ± 12.5%, p < 0.001 vs sham-ES). Second, CS increased the symptom score (22.0 ± 12.1 vs 39.3 ± 11.5, p = 0.001 vs control); taVNS, but not sham-ES, reduced the symptom score (26.0 ± 12.2 vs 38.3 ± 21.6, p = 0.026 vs sham-ES). Third, CS decreased vagal activity assessed from the spectral analysis of heart rate variability (0.21 ± 0.10 vs 0.26 ± 0.11, p < 0.05 vs control) and increased the sympathovagal ratio (4.89 ± 1.94 vs 3.74 ± 1.32, p = 0.048 vs control); taVNS normalized CS-induced suppression in vagal activity (0.27 ± 0.13 vs 0.22 ± 0.10, p = 0.049 vs sham-ES; p > 0.05 vs control) and CS-induced increase in the sympathovagal ratio (3.28 ± 1.61 vs 4.28 ± 2.10, p = 0.042 vs sham-ES; p > 0.05 vs control). CONCLUSION: The noninvasive taVNS improves the CS-induced impairment in gastric pace-making activity, possibly by reversing the detrimental effect of CS on autonomic functions. taVNS may have a therapeutic potential for stress-induced gastric dysmotility.


Asunto(s)
Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago , Humanos , Femenino , Adulto , Voluntarios Sanos , Respuesta al Choque por Frío , Estómago , Nervio Vago/fisiología
6.
Front Pharmacol ; 13: 955421, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36210803

RESUMEN

The goal of the study was to analyze whether WJP can alleviate visceral hypersensitivity in IBS-D model rats. In this study, 36 Sprague-Dawley (SD) rats aged 4 weeks old were randomly divided into two groups: the model group (n = 27) and the control group (n = 9). The rat model of IBS-D was established by modified compound methods for 4 weeks. After the modification, IBS-D rats were randomly divided into three groups, namely, the IBS-D model group (n = 9), the positive drug group (n = 9), and the WJP group (n = 9), with different interventions, respectively. The control group was fed and allowed to drink water routinely. The Bristol stool scale scores were used to assess the severity of diarrhea. Abdominal withdrawal reflex (AWR) scores were used to assess visceral sensitivity. Expression of TNF-α was measured, and histopathological examinations were performed to assess colon inflammation in IBS-D model rats. Key factors of the MEK/ERK signal pathway in the tissue of the colon and hippocampus were measured to analyze the mechanism of WJP. Compared with the control group, the Bristol stool scale scores in the model group were significantly increased (p < 0.0001). The scores of the WJP group were significantly decreased compared with the model group (p = 0.0001). Compared with the control group, AWR scores in the model group at each pressure level were significantly increased (p = 0.0003, p < 0.0001, p = 0.0007, and p = 0.0009). AWR scores of the WJP group were significantly decreased compared with the model group (p = 0.0003, p = 0.0007, p = 0.0007, and p = 0.0009). Compared with the control group, the model group had significantly higher expression of TNF-α in the colon tissue (p < 0.0001). However, the WJP group had significantly lower level of TNF-α compared with the model group (p < 0.0001). Meanwhile, compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue was significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the colon tissue were significantly decreased in the WJP group (p < 0.0001, p = 0.0019, and p = 0.0013). Compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue were significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the hippocampus tissue were significantly decreased in the WJP group (p = 0.0126, p = 0.0291, and p = 0.0145). The results indicated that WJP can alleviate visceral hypersensitivity in IBS-D model rats, possibly mediated by downregulating the expression of TNF-α, p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue. At the same time, WJP also affects downregulating the expression of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue.

7.
Clin Transl Gastroenterol ; 13(5): e00485, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35347091

RESUMEN

INTRODUCTION: Reduced rectal sensation is involved in the pathophysiology of constipation. The aim of this study was to investigate the effects of transcutaneous electrical acustimulation (TEA) at acupuncture point ST36 on constipation and rectal sensation as well as autonomic functions in patients with constipation and reduced rectal sensation. METHODS: In an acute study, anorectal motility and sensation tests were performed in constipation patients (N = 53) who were treated with TEA at ST36 or sham points. In a chronic study, patients (N = 18) underwent 2 weeks of TEA or sham-TEA in a crossover design. RESULTS: Chronic TEA increased spontaneous bowel movements (3.72 vs 2.00 per week with sham-TEA, P < 0.0001) and significantly reduced constipation symptoms and increased quality of life in comparison with sham-TEA (P < 0.05). Acute TEA reduced the sensation threshold in response to rectal distention for the urge of defecation and maximum tolerable volume (P < 0.05, vs baseline); chronic TEA reduced the sensation thresholds for first sensation and desire of defecation, and decreased the threshold volume to an elicit rectal anal inhibitory reflex (P < 0.05). Both acute and chronic TEA increased parasympathetic activity (P < 0.05). DISCUSSION: TEA at ST36 improves chronic constipation by enhancing rectal sensation possibly mediated by the reinforcement of parasympathetic activity in patients with functional constipation and reported lack/absence of rectal sensation.


Asunto(s)
Estreñimiento , Calidad de Vida , Recto , Estimulación Eléctrica Transcutánea del Nervio , Estreñimiento/diagnóstico , Estreñimiento/terapia , Humanos , Sensación
8.
Neuromodulation ; 25(8): 1165-1172, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35088760

RESUMEN

BACKGROUND AND AIM: Patients with diarrhea-dominant irritable bowel syndrome (IBS-D) experience abdominal pain and reduced quality of life and need effective treatments. This study aimed to evaluate whether transcutaneous electrical acustimulation (TEA) at two acupuncture points, LI4 and ST36, could improve pain and quality of life of patients with IBS-D. MATERIALS AND METHODS: A total of 42 patients with IBS-D who met the Rome IV criteria were randomly divided into two groups: TEA and sham-TEA. TEA was performed through acupoints Hegu (LI4) and Zusanli (ST36) for one hour twice daily for one month, using previously established parameters; sham-TEA was delivered in the same way as TEA but without actual electrical current stimulation. RESULTS: The sham-TEA group showed a significantly higher rate of drop-out than the TEA group (29% vs 0%, p = 0.021). TEA, but not sham-TEA, significantly improved quality of life (before: 78.55 ± 9.62, after: 85.97 ± 9.49, p < 0.0001). Both TEA and sham-TEA reduced abdominal pain; however, TEA was more potent than sham-TEA (p = 0.014). The IBS symptom severity scale score was reduced by both TEA and sham-TEA. Autonomic functions assessed by plasma norepinephrine and pancreatic polypeptide were not altered with TEA, nor was interleukin 10 or interleukin 6. CONCLUSIONS: TEA at LI4 and ST36 improves abdominal pain and quality of life of patients with IBS-D, probably mediated by mechanisms other than autonomic function or inflammatory cytokines.


Asunto(s)
Terapia por Acupuntura , Síndrome del Colon Irritable , Humanos , Síndrome del Colon Irritable/terapia , Calidad de Vida , Diarrea/etiología , Diarrea/terapia , Dolor Abdominal/etiología , Dolor Abdominal/terapia
9.
Dig Dis Sci ; 67(4): 1320-1327, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34129127

RESUMEN

BACKGROUND: Biofeedback therapy is highly effective and safe in treating dyssynergic defecation, which affects more than half of patients with chronic constipation. However, conventional biofeedback training has limitations. AIMS: This study aims to modify the adaptive biofeedback (ABF) previously established by the investigators and evaluate its efficacy for dyssynergic defecation. METHODS: A total of 42 constipation patients were enrolled and randomly assigned to receive either 4-week adaptive biofeedback (ABF) training (ABF group), or fixed biofeedback (FBF) training (FBF group). The ABF training program was modified, as follows: (1) the tailored training targets were set according to the ability of the individual subject, instead of the fixed values; (2) the outcome was scored on the basis of the rectal-anal pressure gradient; (3) the feedback information was delivered through multimedia. The outcomes were compared between the two groups. RESULTS: The number of weekly bowel movements (BM) was significantly greater in the ABF group than in the FBF group. The improvement in dyssynergic defecation was also noted with the modified ABF training, which performed significantly better than the conventional training on incomplete defecation, bloating, defecation time, staining, and urgency. Notably, the use of medications was significantly reduced upon completion of the 4-week adaptive training, and this was significantly lesser than that in the fixed training. Furthermore, there was significantly better improvement on anorectal motility and rectal sensation in the ABF group vs. the FBF group. CONCLUSION: The modified ABF training program significantly improves constipation-related symptoms, and its performance is superior to conventional FBF training for dyssynergic defecation.


Asunto(s)
Estreñimiento , Defecación , Ataxia/terapia , Biorretroalimentación Psicológica , Estreñimiento/diagnóstico , Estreñimiento/terapia , Humanos , Manometría
10.
Neuromodulation ; 25(8): 1387-1392, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33638273

RESUMEN

BACKGROUND: In the United States, more than 14 million adults suffer from alcohol use disorder (AUD). We proposed a stress-free method of electroacupuncture (EA) using chronically implanted electrodes. We aimed to develop an effective method of EA for treating AUD by testing various stimulation locations and parameters, and then investigate the effects of the daily EA on alcohol consumption and withdrawal signs in rats. MATERIALS AND METHODS: Sprague-Dawley rats were trained to voluntarily drink ethanol under the intermittent access two-bottle choice procedure. By the end of four weeks, rats with ethanol consumption ≥1.5 g/kg/24 h were considered alcohol-dependent and included in an acute and prolonged experiments. The acute study was designed to investigate the effects of EA with different parameters and at different locations. EA treatment was applied at bilateral ST36 alone or bilateral ST36 and HT7 acupoints for 30 minutes. We investigated the effects of EA on 24-hour alcohol consumption, preference ratio (alcohol drink vs total drink), alcohol withdrawal signs (AWS), and prolonged alcohol consumption. Each animal served as its own control. RESULTS: 1) By the end of week 4, 70% of rats became alcohol-dependent. 2) Following ethanol withdrawal, there was a gradual increase in AWS over time that peaked at two hours and dropped at six hours. Among the tested stimulation parameters and locations: 3) The best stimulation location was ST36 alone, and the best stimulation parameters were a combination of 100 and 2 Hz. EA at best stimulation location and parameters reduced ethanol intake by 27% (p < 0.05 vs baseline) and marginally reduced preference ratio by 23% (p = 0.05 vs baseline). 4) EA reduced AWS at two- and four-hours following ethanol withdrawal (p ≤ 0.03 each vs no EA). 5) Daily EA (for five consecutive days) resulted in a substantial reduction in ethanol intake and preference ratio by 44% and 47%, respectively (p = 0.002 each). CONCLUSIONS: This work shows the potential of this novel method of EA for the treatment of AUD. Further studies are warranted to investigate the mechanisms through which EA exerts its effects.


Asunto(s)
Alcoholismo , Electroacupuntura , Síndrome de Abstinencia a Sustancias , Animales , Ratas , Puntos de Acupuntura , Consumo de Bebidas Alcohólicas/terapia , Alcoholismo/terapia , Electroacupuntura/métodos , Electrodos Implantados , Etanol , Ratas Sprague-Dawley , Síndrome de Abstinencia a Sustancias/etiología , Síndrome de Abstinencia a Sustancias/terapia
11.
Am J Gastroenterol ; 116(7): 1495-1505, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34183577

RESUMEN

INTRODUCTION: Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD. METHODS: Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively. RESULTS: Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD health-related quality of life (P = 0.028) and improved nutrient drink-induced fullness (P < 0.001) and belching (P < 0.001) in patients with GERD. Although only acute TEA significantly enhanced LES pressure (P < 0.05), both acute and chronic TEA remarkedly increased DCI (P < 0.05) and reduced the incidence of ineffective esophageal contractions during wet swallows (P = 0.02). In addition, chronic TEA significantly increased gastric accommodation and the percentage of postprandial normal GSW compared with sham-TEA and baseline. Concurrently, TEA-enhanced vagal activity (P = 0.02) and the vagal activity positively correlated with LES pressure (r = 0.528; P = 0.003) and DCI (r = 0.522; P = 0.003). DISCUSSION: The TEA treatment performed in this study improves reflux-related symptoms, increases DCI, reduces the incidence of ineffective esophageal contractions during wet swallows, and improves gastric accommodation and slow waves. The improvement in GERD symptoms might be attributed to the integrative effects of TEA on these gastroesophageal functions mediated via the vagal mechanism.


Asunto(s)
Puntos de Acupuntura , Terapia por Estimulación Eléctrica/métodos , Trastornos de la Motilidad Esofágica/terapia , Esfínter Esofágico Inferior/fisiopatología , Reflujo Gastroesofágico/terapia , Motilidad Gastrointestinal , Calidad de Vida , Nervio Vago/fisiopatología , Adulto , Sistema Nervioso Autónomo , Técnicas de Diagnóstico del Sistema Digestivo , Electrocardiografía , Trastornos de la Motilidad Esofágica/fisiopatología , Femenino , Reflujo Gastroesofágico/fisiopatología , Frecuencia Cardíaca , Humanos , Masculino , Manometría , Persona de Mediana Edad , Peristaltismo
12.
J Inflamm Res ; 14: 325-339, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33584100

RESUMEN

PURPOSE: The aim of the study was to investigate the effects of electroacupuncture (EA) at ST36 on rectal hypersensitivity and compliance in DSS-treated post-inflammation rats. In addition, we explored the involvement of mast cells-triggered NGF/TrkA/TRPV1 peripheral afferent pathway. METHODS: Rats were provided water with 5% dextran sulphate sodium (DSS) for 7 days. Two weeks after the DSS treatment they were subjected to initial and repetitive EA. Different sets of parameters were compared in the initial test and then EA with the selected parameters were performed for 2 weeks. Rectal compliance was assessed by colorectal distension while visceral sensitivity was evaluated by abdominal withdraw reflexes (AWR) and electromyogram (EMG). Masson's trichrome staining was performed to stain collagen and toluidine blue staining was applied to assess the degranulation of mast cells. Nerve growth factor (NGF), tryptase, TrkA and TRPV1 were measured by Western blot or immunofluorescence staining. RESULTS: EA at 100 Hz was more effective in improving rectal compliance and visceral hypersensitivity. Daily EA improved visceral hypersensitivity but not rectal compliance. Five weeks after DSS treatment, fibrosis was noted in both sham-EA and EA groups. The expression and activation of mast cells were significantly reduced after the 2-week EA treatment with a concurrent decrease in the expression of colonic NGF/TrkA and TRPV1 in both colon and dorsal root ganglions. CONCLUSION: EA at ST36 with a special set of parameters has no effect on reduced rectal compliance but relieves visceral hypersensitivity via the mast cells-triggered NGF/TrkA/TRPV1 peripheral afferent pathway in DSS-treated post-inflammation rats.

13.
Obes Surg ; 31(4): 1664-1672, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33392995

RESUMEN

BACKGROUND: Intestinal electrical stimulation (IES) has been proposed as a potential treatment for obesity. The aim of this study was to explore the central mechanism underlying the reduction of food intake and body weight by IES by studying the expression of anorexigenic- and orexigenic-peptide-containing neurons in the hypothalamus. MATERIALS AND METHODS: Diet-induced obese (DIO) rats were divided into three groups to receive sham, IES, and pair-feeding for 4 weeks. Food intake was measured automatically and presented as daily and body weight measured weekly. The expressions of oxytocin, an anorexigenic neuropeptide, in the paraventricular nucleus of the hypothalamus (PVN) and the supraoptic nuclei of the hypothalamus (SON) and orexin-A, an orexigenic neuropeptide, in the lateral hypothalamic area (LHA) were studied using immunohistochemistry. RESULTS: Compared with sham, IES reduced daily food intake by 28.3% at week 1, 35.6% at week 2, 15.6% at week 3, and 27.1% at week 4. Consistently, IES reduced body weight by 6.3%, compared with a weight gain of 7.2% in sham, and a slight weight loss of 0.5% in pair-feeding. Compared with sham, IES increased the expression of oxytocin-immunoreactive neurons in PVN and SON. Compared with sham, IES decreased the expression of orexin-immunoreactive neurons in LHA. Rats with pair-feeding also showed a relative decease in weight without any changes in the central hormones. CONCLUSION: IES reduces food intake and body weight and improves glucose tolerance and insulin sensitivity in DIO rats. Its central mechanisms involve enhancement of anorexigenic peptides and suppression of orexigenic peptides in the hypothalamus.


Asunto(s)
Obesidad Mórbida , Oxitocina , Animales , Dieta , Ingestión de Alimentos , Estimulación Eléctrica , Hipotálamo , Obesidad/terapia , Obesidad Mórbida/cirugía , Orexinas , Ratas , Ratas Sprague-Dawley
14.
BMC Complement Med Ther ; 20(1): 242, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32738911

RESUMEN

BACKGROUND: At present, ursodeoxycholic acid (UDCA) is internationally recognized as a therapeutic drug in clinic. However, about 40% Primary Biliary Cholangitis (PBC) patients are poor responders to UDCA. It has been demonstrated that Transcutaneous Neuromodulation (TN) can be involved in gut motility, metabolism of bile acids, immune inflammation, and autonomic nerve. Therefore, this study aimed to explore the effect of TN combined with UDCA on PBC and related mechanisms. METHODS: According to inclusion and exclusion criteria, 10 healthy volunteers and 15 PBC patients were recruited to control group and TN group, respectively. PBC patients were alternately but blindly assigned to group A (TN combined with UDCA) and group B (sham-TN combined with UDCA), and a crossover design was used. The TN treatment was performed via the posterior tibial nerve and acupoint ST36 (Zusanli) 1 h twice/day for 2 weeks. T test and nonparametric test were used to analyze the data. RESULTS: 1. TN combined with UDCA improved the liver function of PBC patients shown by a significant decrease of alkaline phosphatase and gamma-glutamyltransferase (γ-GT) (P < 0.05). 2. The treatment also decreased serum IL-6 levels (P < 0.05), but not the level of Tumor Necrosis Factor-α, IL-1ß or IL-10. 3. TN combined with UDCA regulated autonomic function, enhanced vagal activity, and decreased the sympathovagal ratio assessed by the spectral analysis of heart rate variability (P < 0.05). 4. There was no change in 13 bile acids in serum or stool after TN or sham-TN. CONCLUSIONS: TN cssombined with UDCA can significantly improve the liver function of PBC patients. It is possibly via the cholinergic anti-inflammatory pathway. TN might be a new non-drug therapy for PBC. Further studies are required. TRIAL REGISTRATION: The study protocol was registered in Chinese Clinical Trial Registry (number ChiCTR1800014633 ) on 25 January 2018.


Asunto(s)
Inflamación/terapia , Cirrosis Hepática Biliar/terapia , Estimulación Eléctrica Transcutánea del Nervio/métodos , Ácido Ursodesoxicólico/uso terapéutico , Adulto , Colagogos y Coleréticos/uso terapéutico , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Sistema Nervioso Simpático/fisiopatología , Nervio Vago/fisiopatología
15.
Am J Physiol Regul Integr Comp Physiol ; 319(1): R106-R113, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32493036

RESUMEN

Electroacupuncture (EA) is widely used as an effective method to treat stress-related disorders. However, its mechanisms remain largely unknown. The aim of this study was to investigate the effects and mechanisms of EA on gastric slow wave (GSW) dysrhythmia and c-Fos expression in the nucleus of the solitary tract (NTS) induced by stress in a rodent model of functional dyspepsia (FD). Rats in the neonatal stage were treated using intragastric iodoacetamide. Eight weeks later, the rats were implanted with electrodes in the stomach for the measurement of GSW and electrodes into accupoints ST36 for EA. Autonomic functions were assessed by spectral analysis of heart rate variability. Rats were placed for 30 min in a cylindrical plastic tube for acute restraint stress. The involvement of a central afferent pathway was assessed by measuring c-Fos-immunoreactive cells in the NTS. 1) EA normalized restraint stress-induced impairment of GSW in FD rats. 2) EA significantly increased vagal activity (P = 0.002) and improved sympathovagal balance (P = 0.004) under stress in FD rats. 3) In FD rats under restraint stress, plasma norepinephrine concentration was increased substantially (P < 0.01), which was suppressed with EA. 4) The EA group showed increased c-Fos-positive cell counts in the NTS compared with the sham EA group (P < 0.05) in FD rats. Acute restraint stress induces gastric dysrhythmia in a rodent model of FD. EA at ST36 improves GSW under stress in FD rats mediated via the central and autonomic pathways, involving the NTS and vagal efferent pathway.


Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Sistema Nervioso Central/fisiopatología , Dispepsia/fisiopatología , Dispepsia/terapia , Electroacupuntura , Gastropatías/terapia , Estrés Psicológico/complicaciones , Vías Aferentes/fisiopatología , Animales , Animales Recién Nacidos , Vaciamiento Gástrico , Yodoacetamida , Masculino , Norepinefrina/sangre , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Ratas , Ratas Sprague-Dawley , Restricción Física , Núcleo Solitario/metabolismo , Gastropatías/inducido químicamente , Nervio Vago/fisiopatología
16.
Neurogastroenterol Motil ; 32(10): e13916, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32537873

RESUMEN

BACKGROUND: The mucosal barrier damage is recognized as one of the key factors in the pathogenesis of colitis. While sacral nerve stimulation (SNS) was reported to have therapeutic potential for colitis, its mechanisms of actions on colonic permeability remained largely unknown. METHODS: In this study, colitis was induced by intrarectal administration of TNBS in rats. Five days later, they were treated with SNS or sham-SNS for 10 days. The effects of SNS on colonic permeability were assessed by measuring the expression of tight-junction proteins involved in regulating permeability and the FITC-dextran test. The mechanism of actions of SNS was investigated by studying the function of the enteric nervous system (ENS) cells and analyzing the autonomic nervous system. KEY RESULTS: SNS decreased the disease activity index, microscopic and macroscopic scores, myeloperoxidase activity, and pro-inflammatory cytokines (TNF-α, IL-6). SNS increased the expression of Zonula Occludens-1, Occludin, Claudin-1, and Junctional adhesion molecule-A in the colon tissue. The FITC-dextran test showed that the colonic permeability was lower with SCS than sham-SNS. SNS increased ChAT, pancreatic polypeptide, and GDNF and reduced norepinephrine NGF, sub-P, and mast cell overactivation in the colon tissue. Concurrently, SNS increased acetylcholine in colon tissues and elevated vagal efferent activity. CONCLUSIONS & INFERENCES: SNS ameliorates colonic inflammation and enhances colonic barrier function with the proposed mechanisms involving the increase in parasympathetic activity and modulation of the activity of the ENS and immune system, including mast cells.


Asunto(s)
Colitis/fisiopatología , Colitis/terapia , Modelos Animales de Enfermedad , Terapia por Estimulación Eléctrica/tendencias , Plexo Lumbosacro/fisiología , Animales , Colitis/inducido químicamente , Terapia por Estimulación Eléctrica/instrumentación , Electrodos Implantados/tendencias , Plexo Lumbosacro/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Roedores , Ácido Trinitrobencenosulfónico/toxicidad
17.
Neurogastroenterol Motil ; 32(6): e13825, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32115817

RESUMEN

BACKGROUND: Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms. METHODS: Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS-0.5h daily, SNS-1h daily, and SNS-3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz-210 µs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed. KEY RESULTS: Both SNS-1h and SNS-3h significantly ameliorated intestinal inflammation; SNS-1h was superior to SNS-3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity. CONCLUSION & INFERENCES: Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the modulation of the autonomic function.


Asunto(s)
Colitis/prevención & control , Terapia por Estimulación Eléctrica/métodos , Plexo Lumbosacro/fisiología , Animales , Colitis/sangre , Citocinas/sangre , Masculino , Norepinefrina/sangre , Polipéptido Pancreático/sangre , Ratas Sprague-Dawley
18.
Physiol Rep ; 8(1): e14294, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31925899

RESUMEN

Neuromodulation based on the vagal anti-inflammatory reflex has emerged as an exciting therapeutic approach for chronic inflammatory diseases. However, it is unclear whether direct stimulation of the vagus or of pelvic nerves coming from sacral roots, providing the bulk of colonic parasympathetic innervation, is the best approach. We hypothesized that sacral nerve stimulation (SNS) would be an effective treatment for colitis. Age and sex-matched Sprague-Dawley rats were administered 5% dextran sulphate sodium (DSS) in drinking water ad libitum for 7 days. A group of rats was sacrificed after DSS treatment, and the remaining rats were randomized to either sham-SNS or SNS groups, which were performed for 1 hr daily for 10 days. Stimulations were delivered via chronically implanted electrodes using an 8-channel universal pulse generator. Sacral nerve stimulation promoted recovery of colitis demonstrated by decreased disease activity index, myeloperoxidase activity, tissue TNF-alpha, and histological scores as well as an increased colonic M2 macrophage population. Heart rate variability analysis demonstrated a decrease in low frequency and increase in high frequency with SNS, corresponding to increased vagal tone. Additionally, plasma pancreatic peptide was increased and norepinephrine was decreased after SNS in colitis while colon tissue acetylcholine was increased with SNS. This is the first study to the best of our knowledge that demonstrates the benefit of SNS with autonomic mediation. SNS alters the expression of inflammatory cytokines and macrophages as well as modulates neurotransmitters involved in systemic inflammation.


Asunto(s)
Colitis/terapia , Colon/patología , Terapia por Estimulación Eléctrica/métodos , Plexo Lumbosacro , Neuroinmunomodulación , Animales , Colitis/metabolismo , Colitis/patología , Colon/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Frecuencia Cardíaca , Macrófagos/patología , Sistema Nervioso Parasimpático , Peroxidasa/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Nervios Espinales , Factor de Necrosis Tumoral alfa/metabolismo
19.
Inflamm Bowel Dis ; 26(8): 1119-1130, 2020 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-31782957

RESUMEN

Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the digestive tract that is often debilitating. It affects patients' quality of life and imposes a financial burden. Despite advances in treatment with medications such as biologics, a large proportion of patients do not respond to medical therapy or develop adverse events. Therefore, alternative treatment options such as electrical neuromodulation are currently being investigated. Electrical neuromodulation, also called bioelectronic medicine, is emerging as a potential new treatment for IBD. Over the past decade, advancements have been made in electrical neuromodulation. A number of electrical neuromodulation methods, such as vagus nerve stimulation, sacral nerve stimulation, and tibial nerve stimulation, have been tested to treat IBD. A series of animal and clinical trials have been performed to evaluate efficacy with promising results. Although the exact underlying mechanisms of action for electrical neuromodulation remain to be explored, this modality is promising. Further randomized controlled trials and basic experiments are needed to investigate efficacy and clarify intrinsic mechanisms.


Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Tracto Gastrointestinal/inervación , Enfermedades Inflamatorias del Intestino/terapia , Animales , Humanos , Enfermedades Inflamatorias del Intestino/fisiopatología , Sacro/inervación , Nervio Vago/fisiopatología
20.
Am J Physiol Gastrointest Liver Physiol ; 317(5): G609-G617, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31411502

RESUMEN

Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, its effects are limited, and mechanisms are largely unknown. We investigated the effects and mechanism of SNS with appropriate parameters on constipation in rats treated with loperamide. First, using rectal compliance as an outcome measure, an experiment was performed to derive effective SNS parameters. Then, a 7-day SNS was performed in rats with constipation induced by loperamide. Autonomic functions were assessed by spectral analysis of heart rate variability (HRV) derived from an electrocardiogram. Serum levels of pancreatic polypeptide (PP), norepinephrine (NE), and acetylcholine (ACh) in colon were assessed. 1) Acute SNS at 5 Hz, 100 µs was found effective in enhancing rectal compliance and accelerating distal colon transit (P < 0.05 vs. sham SNS). 2) The 7-day SNS normalized loperamide-induced constipation, assessed by the number, weight, and water content of fecal pellets, and accelerated the distal colon transit (29.4 ± 3.7 min with sham SNS vs. 16.4 ± 5.3 min with SNS but not gastric emptying or intestinal transit. 3) SNS significantly increased vagal activity (P = 0.035) and decreased sympathetic activity (P = 0.012), assessed by spectral analysis of HRV as well as by the serum PP. 4) SNS increased ACh in the colon tissue; atropine blocked the accelerative effect of SNS on distal colon transit. We concluded that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility, mediated via the autonomic-cholinergic function.NEW & NOTEWORTHY Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, effects are limited, and mechanisms are largely unknown. This paper shows that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility mediated via the autonomic-cholinergic function.


Asunto(s)
Colon/fisiología , Estreñimiento/terapia , Terapia por Estimulación Eléctrica/métodos , Tránsito Gastrointestinal , Plexo Lumbosacro/fisiología , Acetilcolina/metabolismo , Animales , Sistema Nervioso Autónomo/fisiología , Colon/inervación , Colon/metabolismo , Estreñimiento/etiología , Loperamida/toxicidad , Masculino , Norepinefrina/sangre , Polipéptido Pancreático/sangre , Ratas , Ratas Sprague-Dawley
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