Neurogastroenterology and motility disorders of the upper gastrointestinal (GI) tract represent a complex and heterogeneous group of conditions that involve the interaction between the GI tract and the central nervous system. They constitute a significant number of outpatient gastroenterology visits, resulting in a high healthcare burden. These disorders often occur in the absence of identifiable structural causes on routine endoscopy and radiological imaging. A more targeted approach in the assessment of functional GI disorders is increasingly being integrated into routine clinical practice, given the recent advancements in technology and physiologic testing. When used in the appropriate clinical context, these tests not only elucidate the physiological basis for the patient's symptoms, but also prevent inappropriate treatment and repeated investigations. This review aims to summarise the advances in clinically available diagnostic tools for the evaluation of upper GI functional disorders.
Humans ; Gastrointestinal Diseases/physiopathology* ; Upper Gastrointestinal Tract/physiopathology* ; Gastrointestinal Motility ; Endoscopy, Gastrointestinal

OBJECTIVE: To observe the distribution characteristics of sensitization areas on the body surface in the rat models with functional constipation and diarrhea, explore the regulatory patterns of electroacupuncture (EA) of different intensities at "Tianshu" (ST25) on distal colon motility, and clarify the roles of the neurons of different subtypes in the enteric nervous system (ENS) displayed in the regulatory effect. METHODS: Of 90 SD male rats of SPF grade, 15 rats were randomized into a normal group, a constipation group and a diarrhea group, 5 rats in each one. The stool form and fecal water content, as well as the distribution of the Evans blue (EB) extravasation on the body surface after the intravenous injection with EB on the tails were observed. Eighteen rats were randomized into a normal +2 mA group, a normal +4 mA group and a normal + 6 mA group, 6 rats in each one. Using physiological signal acquisition system, the area under the curve and the average amplitude of colon peristalsis were recorded and analyzed, and the immediate effect on distal colon peristalsis observed after EA with different intensities at "Tianshu" (ST25). Thirty rats were randomized into a normal group, a constipation group, a diarrhea group, a constipation +2 mA group, and a diarrhea +6 mA group, 6 rats in each one, so as to observe the cumulative effect on colon motility disorder in the rat models of constipation and diarrhea after EA at "Tianshu" (ST25). Twelve rats were randomized into a constipation +2 mA group and a diarrhea +6 mA group, 6 rats in each one, to observe the immediate effect on colon motility disorder in the rat models of constipation and diarrhea after EA at "Tianshu" (ST25). Fifteen rats were randomly divided into a normal group, a constipation group, a diarrhea group, a constipation +2 mA group, and a diarrhea + 6 mA group, 3 rats in each one. Using the whole-mount staining technique, the expression of vesicular acetylcholine transporter (VAChT)-positive neurons and nitric oxide synthase (nNOS)-positive neurons in ENS was detected. According to the group divisions, the functional constipation models were established by intragastric administration of loperamide hydrochloride (10 mg/kg, once daily, for consecutive 7 days), and the functional diarrhea models were prepared by intragastric administration of folium sennae decoction (10 mL/kg, once daily, for consecutive 2 days). The interventions were delivered with EA of different intensities (the electric current of 2, 4 or 6 mA) at bilateral "Tianshu" (ST25), separately, with the continuous wave and the frequency of 10 Hz used. RESULTS: Compared with the normal group, the fecal amount was decreased, and the fecal water content was reduced in the rats of the constipation group (P<0.001); and loose stool was presented and the fecal water content increased in rats of the diarrhea group (P<0.001). EB extravasation on the body surface happened in the region from T₆ to S₂ of the rats in the constipation and diarrhea groups, and it was more concentrated in the lower abdominal and the lower back regions from T₁₀ to L₃. Compared with the indexes before EA, in the normal +2 mA group and the normal +4 mA group, the areas under the curve and the average amplitude of the distal colon peristalsis were higher during EA delivery (P<0.01, P<0.05), showing a stimulatory immediate effect; and the post-effect was obtained after EA at 2 mA. Whereas, these two indexes were declined during EA in the rats of the normal +6 mA group (P<0.001), showing an inhibitory immediate effect. After many interventions with EA, when compared with those before EA, the above two indexes rose in the constipation +2 mA group (P<0.05, P<0.01), and they were dropped in the diarrhea +6 mA group (P<0.01, P<0.05). The area under the curve of the colon peristalsis in the constipation +2 mA group was higher than that of the constipation group (P<0.001), and that in the diarrhea +6 mA group was lower compared with that in the diarrhea group (P<0.001). The stimulatory effect of EA on colon motility in the constipation +2 mA group was stronger than that of the normal + 2 mA group (P<0.05), and its inhibitory effect was not different statistically in comparison between the normal +6 mA group and the diarrhea +6 mA group (P>0.05). In ENS of the distal colon, after EA at 2 mA, the proportion of VAChT-positive neurons was higher than that of the activated nNOS-positive neurons (P<0.001); and after EA at 6 mA, the activated nNOS-positive neurons were dominant (P<0.001). CONCLUSION In the functional constipation and diarrhea rat models, the sensitization areas on the body surface are centralized in the lower abdominal and the lower back regions of T₁₀ to L₃. Electroacupuncture at "Tianshu" (ST25) has a bidirectional regulatory effect on distal colon motility, and this effect is coordinated with the intensity of electroacupuncture, and may be mediated by ENS neurons of different subtypes.
Animals ; Electroacupuncture ; Male ; Rats ; Colon/innervation* ; Acupuncture Points ; Rats, Sprague-Dawley ; Constipation/physiopathology* ; Gastrointestinal Motility ; Humans ; Diarrhea/physiopathology*

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) in treating diabetic gastroparesis (DGP) by inhibiting the activation of Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and pyroptosis mediated via NLRP3/cysteinyl aspartate specific proteinase-1 (caspase-1)/gasdermin D (GSDMD) signaling pathway. METHODS: Forty Sprague-Dawley rats were randomly divided into 4 groups including the control, DGP model, EA, and MCC950 groups. The DGP model was established by a one-time high-dose intraperitoneal injection of 2% streptozotocin and a high-glucose and high-fat diet for 8 weeks. EA intervention was conducted at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) with sparse-dense wave for 15 min, and was administered for 3 courses of 5 days. After intervention, the blood glucose, urine glucose, gastric emptying, and intestinal propulsive rate were observed. Besides, HE staining was used to observe histopathological changes in gastric antrum tissues, and TUNEL staining was utilized to detect DNA damage. Protein expression levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, caspase-1 and GSDMD were measured by Western blot. Immunofluorescence staining was employed to assess the activity of GSDMD-N. Lactate dehydrogenase (LDH) levels were detected by using a biochemical kit. RESULTS: DGP rats showed persistent hyperglycemia and a significant decrease in gastrointestinal motility (P<0.05 or P<0.01), accompanied by pathological damage in their gastric antrum tissues. Cellular DNA was obviously damaged, and the expressions of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD proteins were significantly elevated, along with enhanced fluorescence signals of GSDMD-N and increased LDH release (P<0.01). EA mitigated hyperglycemia, improved gastrointestinal motility in DGP rats and alleviated their pathological injury (P<0.05). Furthermore, EA reduced cellular DNA damage, lowered the protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD, suppressed GSDMD-N activity, and decreased LDH release (P<0.05 or P<0.01), demonstrating effects comparable to MCC950. CONCLUSION EA promotes gastrointestinal motility and repairs the pathological damage in DGP rats, and its mechanism may be related to the inhibition of NLRP3 inflammasome and pyroptosis mediated by NLRP3/caspase-1/GSDMD pathway.
Animals ; Electroacupuncture ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Gastroparesis/physiopathology* ; Signal Transduction ; Male ; Diabetes Mellitus, Experimental/physiopathology* ; Phosphate-Binding Proteins/metabolism* ; Gastrointestinal Motility ; Rats ; Intracellular Signaling Peptides and Proteins/metabolism* ; Diabetes Complications/physiopathology* ; Gasdermins

OBJECTIVE: Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. METHODS: A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. RESULTS: EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. CONCLUSION EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture ; Animals ; Male ; Acupuncture Points ; Stomach Diseases/physiopathology* ; Rats, Sprague-Dawley ; Gastrointestinal Motility ; Rats ; Gastric Emptying ; Neurons ; Spinal Cord ; Stomach/physiopathology*

OBJECTIVE: Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved. METHODS: Transgenic mice were used to trace Nestin⁺/nerve growth factor receptor (Ngfr)⁺ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms. RESULTS: EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein⁺ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice. CONCLUSION EA facilitates ENS repair by promoting Nestin⁺/Ngfr⁺ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin⁺/Ngfr⁺ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals ; Electroacupuncture ; Enteric Nervous System/physiology* ; Gastrointestinal Motility/physiology* ; Glial Cell Line-Derived Neurotrophic Factor/metabolism* ; Diabetes Mellitus, Experimental/therapy* ; Signal Transduction ; Mice ; Gastrointestinal Diseases/physiopathology* ; Proto-Oncogene Proteins c-ret/metabolism* ; Mice, Transgenic ; Male ; Nerve Regeneration ; Neural Stem Cells ; Mice, Inbred C57BL ; Acupuncture Points

Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semi-automatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-1β), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3⁺ T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-1β in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.
Humans ; Rats ; Male ; Animals ; Gastrointestinal Microbiome ; Lipopolysaccharides/pharmacology* ; RNA, Ribosomal, 16S ; Semen ; Sperm Motility ; Infertility, Male/prevention & control* ; Testosterone

In recent years, colonic manometry has been gradually introduced into clinical practice. It helps clinicians to gain a better understanding of the physiology and pathophysiology of colonic contractile activity in healthy adults and patients with colonic dysfunction. More and more patterns of colonic motility are being discovered with the help of colonic manometry. However, the clinical significance of these findings still needs to be further investigated. This review enhances our understanding of colonic motility and the current state of development and application of colonic manometry, as well as the limitations, future directions and potential of the technique in assessing the impact of treatment on colonic motility patterns, by analyzing and summarizing the literature related to colonic manometry.
Humans ; Adult ; Gastrointestinal Motility/physiology* ; Colon/physiology* ; Colonic Diseases ; Manometry/methods* ; Clinical Relevance ; Constipation

Gastrointestinal Motility ; Parasympathetic Nervous System

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) combined with mosapride on gastric emptying rate and gastric motility in the rats with diabetic gastroparesis. METHODS: Using random number table method, 68 male SD rats were divided into a blank group (12 rats) and a model establishment group (56 rats). In the model establishment group, the models of diabetic gastroparesis were established with intraperitoneal injection of streptozotocin combined with high-fat and high-sugar diet. Six weeks later, the successful rat models in the model establishment group were randomized into a model group, an EA group, a mosapride group and a combined treatment group, 12 rats in each one. In the EA group, EA was exerted at "Zusanli" (ST 36) (disperse-dense wave, 2 Hz/15 Hz in frequency, 2 mA in intensity) for 20 min. In the mosapride group, mosapride was intervened with intragastric administration (2 mg/kg). In the combined treatment group, electroacupuncture at "Zusanli" (ST 36) was combined with intragastric administration of mosapride. The intervention was given once daily in each group. There was 1 day at interval after 6-day intervention, consecutively for 5 weeks. At the end of intervention, the random blood glucose, gastric emptying rate and the data of gastric motility (average intra-gastric pressure, amplitude and frequency of gastric motility) were detected. RESULTS: Compared with the blank group, blood glucose was increased in the model group (P<0.001). Blood glucose was reduced in the EA group, the mosapride group and the combined treatment group as compared with the model group separately (P<0.001, P<0.01), whereas, compared with the mosapride group, blood glucose was decreased in the combined treatment group (P<0.05). In comparison with the blank group, the gastric emptying rate, the average intra-gastric pressure and the amplitude of gastric motility were all decreased in the model group (P<0.001) and the frequency of gastric motility was increased (P<0.001). Gastric emptying rate, the average intra-gastric pressure and the amplitude of gastric motility were increased in the EA group, the mosapride group and the combined treatment group (P<0.01, P<0.05, P<0.001) and the frequency of gastric motility was decreased (P<0.001) as compared with the model group respectively. Compared with the EA group, the average intra-gastric pressure and the amplitude of gastric motility were increased in the combined treatment group (P<0.001). In comparison with the mosapride group, the gastric emptying rate, the average intra-gastric pressure, the amplitude and frequency of gastric motility in the combined treatment group, as well as the frequency of gastric motility in the EA group were all increased (P<0.05, P<0.001, P<0.01). CONCLUSION Electroacupuncture at "Zusanli" (ST 36) combined with intragastric administration of mosapride could regulate blood glucose and improve the gastric motility in the rats with diabetic gastroparesis. The effect is better than either simple electroacupuncture or mosapride.
Acupuncture Points ; Animals ; Benzamides ; Diabetes Mellitus/therapy* ; Electroacupuncture ; Gastrointestinal Motility/physiology* ; Gastroparesis/etiology* ; Male ; Morpholines ; Rats ; Rats, Sprague-Dawley

From the perspective of autonomic nervous system, this paper analyzes the mechanism, current western medicine treatment methods and acupuncture-moxibustion treatment mechanism of gastroesophageal reflux disease (GERD). It is believed that the main cause of GERD is that the gastric acid goes to the wrong place due to gastrointestinal motility disorder, which belongs to "acid dislocation". At present, western medical treatment cannot effectively target the pathogenesis of the disease, and its effect is limited. Acupuncture-moxibustion could regulate the neuroendocrine immune network to regulate the function of autonomic nerve, restore the power of digestive tract to treat GERD, which is worthy of further research.
Humans ; Moxibustion ; Acupuncture Therapy ; Gastroesophageal Reflux/therapy* ; Gastrointestinal Diseases ; Autonomic Nervous System ; Gastrointestinal Motility