OBJECTIVES: To investigate the neuroprotective effects of electroacupuncture (EA) preconditioning against cerebral ischemia-reperfusion injury (CIRI) mediated by gut microbiota modulation, Nrf2/HO-1 pathway activation, and ferroptosis suppression. METHODS: Adult male SD rats were divided into sham operation group, CIRI model group, and EA preconditioning group. In the latter two groups, rat models of CIRI were established by middle cerebral artery occlusion (MCAO), and in EA preconditioning group, EA was applied at Baihui (DU20) and Zusanli (ST36) for 3 days before modeling. Neurological deficits, cerebral infarction, and hippocampal pathology of the rats were evaluated using behavioral tests, TTC staining, and Nissl and HE staining, and the oxidative stress markers (MDA, ROS, and SOD), apoptosis/ferroptosis-related proteins (Bax, Bcl-2, GPX4, and SLC7A11), and changes in gut microbiota were analyzed. RESULTS: EA preconditioning significantly reduced neurological deficits, decreased infarct volume, promoted hippocampal neuronal survival, and improved structural integrity of the hippocampal neurons in MCAO rats. EA preconditioning also significantly lowered MDA and ROS and increased SOD levels, upregulated Bcl-2, GPX4, and SLC7A11 expressions, and downregulated Bax expression in the hippocampal tissue of the rats, causing also activation of Nrf2/HO-1 signaling and improvement of gut microbiota composition. CONCLUSIONS EA preconditioning alleviates CIRI in rats by suppressing ferroptosis and apoptosis, enhancing antioxidant defenses via activating Nrf2/HO-1 signaling, and regulating the gut-brain axis.
Animals ; Electroacupuncture ; NF-E2-Related Factor 2/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Reperfusion Injury/therapy* ; Ferroptosis ; Male ; Rats ; Brain Ischemia ; Gastrointestinal Microbiome ; Heme Oxygenase (Decyclizing)/metabolism* ; Brain/metabolism* ; Oxidative Stress ; Heme Oxygenase-1/metabolism* ; Apoptosis

OBJECTIVES: To explore the effects of acupuncture combined with rehabilitation training for promoting transdifferentiation of astrocytes into neurons in mice after cerebral ischemia. METHODS: Male C57/BL6J mice were subjected to intracerebral microinjection of an adeno-associated virus carrying the GFAP promoter for NeuroD1 and Ngn2 overexpression in the astrocytes, followed 3 or 12 days later by electrocoagulation of the distal middle cerebral artery. After modeling, the mice were randomly divided into model group without interventions and intervention group treated with electroacupuncture at the acupoints Baihui (GV20), left Hegu (LI4), Neiguan (PC6), Zusanli (ST36), and Yanglingquan (GB34) 24 h after surgery. The mice in the intervention group were housed individually in cages with running wheels, and their activity was recorded every 24 h. Neurological function scores of the mice were assessed on the 1st, 14th, and 21st days after modeling. Transdifferentiation of astrocytes in the target brain regions was observed using double immunofluorescence staining. RESULTS: Compared with those in the model group, the mice receiving eletroacupuncture and rehabilitation training showed significant improvement of neurological deficits at 14 and 21 days after modeling. The GFAP promoter of the AAV2/5 vector specifically labeled the local astrocytes, and compared with that that in the model group, the number of AAV-positive cells colabeled with the neuronal marker DCX significantly increased after 14 days of electroacupuncture and rehabilitation intervention, and the number of AAV-positive cells colabeled with the neuronal marker NeuN significantly increased after 21 days of intervention. CONCLUSIONS In mice with cerebral ischemia, electroacupuncture and rehabilitation training can promote transdifferentiation of astrocytes into neurons in the ischemic brain region, and the efficiency of transdifferentiation is positively correlated with the improvement of motor function.
Animals ; Electroacupuncture ; Astrocytes/cytology* ; Cell Transdifferentiation ; Male ; Mice, Inbred C57BL ; Brain Ischemia/physiopathology* ; Mice ; Neurons/cytology* ; Doublecortin Protein

OBJECTIVES: To clarify the role of hippocampal glutamate system in regulating HPA axis in mediating the effect of electroacupuncture (EA) at the heart meridian for improving myocardial injury in rats with acute myocardial ischemia (AMI). METHODS: Male SD rats were randomized into sham-operated group, AMI group, EA group, and L-glutamic acid+EA group (n=9). Rat models of AMI were established by left descending coronary artery ligation, and EA was applied at the "Shenmen-Tongli" segment; the rats in L-glutamic acid+EA group were subjected to microinjection of L-glutamic acid into the bilateral hippocampus prior to AMI modeling and EA treatment. Cardiac functions of the rats were evaluated using echocardiography, and ECG and heart rate variation (HRV) were analyzed using PowerLab and LabChart. Pathological changes in the myocardial tissue was examined using HE staining, and serum levels of myocardial enzymes were detected with ELISA. Myocardial expressions of TH and GAP43 were detected with immunohistochemistry, and colocalization of VGLUT1, VGLUT2 and c-fos were observed using immunofluorescence staining; the expressions of VGLUT1, VGLUT2, NMDAR1 and NMDAR2B were detected using Western blotting. RESULTS: The rat models of AMI showed significantly decreased LVEF and LVFS and increased serum levels of myocardial enzymes in positive correlation with the HPA axis. Numerous TH- and GAP43-positive cells were observed in the hippocampus, where the expressions of NE and E, neurons colabeled with VGLUT1, VGLUT2 and c-fos, and expressions of VGLUT1, VGLUT2, NMDAR1, NMDAR2B and Glu increased significantly. All these changes were significantly improved by interventions with EA as compared with those in AMI and L-Glutamate+EA groups. CONCLUSIONS In rats with AMI, EA at the heart meridian can regulate excessive glutamate release in the hippocampus, thereby inhibiting HPA axis hyperactivity and reducing sympathetic nerve activity to protect the myocardial tissue.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Hippocampus/metabolism* ; Rats ; Glutamic Acid/metabolism* ; Myocardial Ischemia/physiopathology* ; Hypothalamo-Hypophyseal System/physiopathology* ; Pituitary-Adrenal System/physiopathology* ; Receptors, N-Methyl-D-Aspartate/metabolism*

OBJECTIVES: To investigate the therapeutic effect of electroacupuncture (EA) at Zusanli (ST36) acupoint on hyperlipidemia in mice and explore the underlying mechanisms. METHODS: Thirty C57BL/6J mice were equally randomized into normal diet group, high-fat diet (HFD) group, and EA group. The changes in blood lipids and serum malondialdehyde (MDA) content of the mice were evaluated, and histopathological changes and lipid accumulation in the liver were observed using Oil red O staining (ORO). The expressions of NLRP3, TLR4, and IL-1β proteins in the colon tissues were detected with Western blotting, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: In mice with HFD feeding, 16 weeks of EA treatment significantly lowered body weight and serum TC, TG, LDL-C and MDA levels, obviously reduced lipid accumulation in the liver, and ameliorated HFD-induced elevations of protein expressions of NLRP3, TLR4, and IL-1β. 16S rRNA sequencing revealed that EA significantly altered gut microbiota composition, and increased the diversity and relative abundance of beneficial bacterial groups such as Muribaculaceae and Lachnospiraceae NK4A136_group. CONCLUSIONS Electroacupuncture at ST36 alleviates blood lipid disorders in hyperlipidemic mice possibly by improving intestinal microbiota structure, promoting degradation of high-caloric carbohydrates, cholesterol lipid metabolism and intestinal mucosa repair, and reducing toxin leakage, lipid peroxides, and liver fat deposition.
Animals ; Electroacupuncture ; Gastrointestinal Microbiome ; Hyperlipidemias/blood* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat ; Toll-Like Receptor 4/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Acupuncture Points ; Male ; Lipids/blood* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

OBJECTIVES: To investigate the mechanism underlying the therapeutic effect of electroacupuncture (EA) on post-traumatic stress disorder (PTSD) in rats. METHODS: Forty male SD rats were randomized equally into blank control group, PTSD model group, sham-acupuncture group, paroxetine group, and EA group. In the latter 3 groups, the rat models of PTSD, induced by continuous single-prolonged stress and plantar electrical stimulation, were treated with EA at GV20, GV24, BL18 and BL23 acupoints for 15 min (5 times a week for 3 weeks), sham-acupuncture without electrical stimulation, or gavage with paroxetine suspension on the same schedule. Behavioral changes of the rats were evaluated using open field test (OFT) and elevated plus maze (EPM) test. Hippocampal pathologies and neuronal changes were examined with HE and Nissl staining, and mitochondrial ultrastructure was examined using electron microscopy. The mRNA and protein expression levels of Bcl-2, Bax, and caspase-3 were detected by RT-qPCR and immunofluorescence staining. RESULTS: The rat models of PTSD showed significantly reduced total distance traveled in OFT and distance and time spent in the open arms of the EPM, with decreased hippocampal neurons, obvious neuronal and mitochondrial pathologies, decreased hippocampal expression of Bcl-2, and increased Bax and caspase-3 expressions. Treatments with paroxetine and EA both significantly improved behavioral changes of the rat models, increased the number of Nissl-stained neurons, obviously alleviated pathologies in the hippocampal neurons and mitochondrial ultrastructure, increased hippocampal Bcl-2 expression, and lowered caspase-3 expressions. Paroxetine showed significantly better effect than EA for improving performance of the rats in EPM test, whereas sham-acupuncture did not produce any significant improvement. CONCLUSIONS EA alleviates PTSD in rats possibly by upregulating Bcl-2 and downregulating Bax and caspase-3, thereby ameliorating hippocampal mitochondrial damage.
Animals ; Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Hippocampus/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Mitochondria/pathology* ; Signal Transduction ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal

OBJECTIVE: To explore the preventive effect of transcutaneous phrenic nerve stimulation on ventilator-induced diaphragmatic dysfunction (VIDD) in patients requiring invasive mechanical ventilation. METHODS: A randomized controlled trial was conducted. The patients requiring invasive mechanical ventilation admitted to the intensive care unit (ICU) of Jiaxing First Hospital from November 2022 to December 2023 were enrolled. Participants were randomized into the control group and the observation group using a random number table. The control group was given ICU standardized nursing intervention, including turning over and slapping the back, raising the head of the bed, sputum aspiration on demand, aerosol inhalation, oral care, and monitoring of airbag pressure and gastric retention, the observation group was given additional transcutaneous phrenic nerve stimulation intervention on the basis of ICU standardized nursing intervention. The stimulation intensity was set to 10 U, the pulse frequency was set to 40 Hz, and the stimulation frequency was set to 12 times/min. Transcutaneous phrenic nerve stimulation was administered once a day for 30 minutes each time, for a total of 5 days. Diaphragm thickening fraction (DTF) and arterial blood gas parameters on days 1, 3, and 5 of intervention were compared between the two groups. After 5 days of intervention, other parameters including the incidence of VIDD, duration of mechanical ventilation, and length of ICU stay were compared. RESULTS: A total of 120 patients requiring invasive mechanical ventilation were enrolled, with 16 dropouts (dropout rate was 13.33%). Ultimately, 51 patients in the control group and 53 patients in the observation group were analyzed. Baseline characteristics, including gender, age, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score, albumin (Alb), hemoglobin (Hb), and disease type, showed no significant differences between the two groups. DTF in both groups gradually increased over duration of intervention [DTF on days 1, 3, and 5 in the control group was (20.83±2.33)%, (21.92±1.27)%, and (23.93±2.33)%, respectively, and that in the observation group was (20.89±1.96)%, (22.56±1.64)%, and (25.34±2.38)%, respectively], with more significant changes in DTF in the observation group, showing time effects (F_time = 105.975, P < 0.001), intervention effects (F_intervention = 7.378, P = 0.008), and interaction effects (F_interaction = 3.322, P = 0.038). Arterial blood gas parameters did not differ significantly before intervention between the groups, but after 5 days of intervention, arterial partial pressure of oxygen (PaO₂) in the observation group was significantly higher than that in the control group [mmHg (1 mmHg≈0.133 kPa): 100.72±15.75 vs. 93.62±15.54, P < 0.05], and arterial partial pressure of carbon dioxide (PaCO₂) was significantly lower than that in the control group (mmHg: 36.53±3.10 vs. 37.69±2.02, P < 0.05). At 5 days of intervention, the incidence of VIDD in the observation group was significantly lower than that in the control group [15.09% (8/53) vs. 37.25% (19/51), P < 0.05], and both duration of mechanical ventilation and length of ICU stay were significantly shorter than those in the control group [duration of mechanical ventilation (days): 7.93±2.06 vs. 8.77±1.76, length of ICU stay (days): 9.64±2.35 vs. 11.01±2.01, both P < 0.05]. CONCLUSIONS Transcutaneous phrenic nerve stimulation can improve diaphragmatic and respiratory function in patients receiving invasive mechanical ventilation, reduce the incidence of VIDD, and shorten the duration of mechanical ventilation and length of ICU stay.
Humans ; Transcutaneous Electric Nerve Stimulation ; Respiration, Artificial/adverse effects* ; Diaphragm/physiopathology* ; Phrenic Nerve ; Intensive Care Units ; Male ; Female ; Middle Aged

OBJECTIVE: To evaluate the advantages and limitations of transcutaneous electrical acupoint stimulation (TEAS) in the treatment of patients with severe gastrointestinal function injury in intensive care unit (ICU) by analyzing dynamic changes of intestinal fatty acid binding protein (I-FABP), D-lactic acid and citrulline. METHODS: A prospective single-center randomized controlled trial was conducted. Patients with severe gastrointestinal function injury admitted to the ICU from February 2021 to January 2024 were enrolled [age > 18 years old, acute gastrointestinal injury (AGI) grade 2 to 3, stable hemodynamics]. Patients with different AGI grades were randomly assigned in a 1:1 ratio to the TEAS group and the control group using simple randomization. Both groups received conventional treatment and enteral nutrition (EN). In addition, the TEAS group underwent TEAS at the Neiguan and Zusanli points for 30 minutes per session, twice daily for 7 days. Baseline data, including age, gender, underlying diseases, and primary diagnoses, were recorded. Three intestinal biomarkers, such as I-FABP, D-lactic acid, and citrulline were measured before and after 7 days of treatment. EN tolerance indicators and 28 days survival status were documented. The differences in various indicators were compared between the two groups, subgroup analyses were conducted based on AGI grading, and interaction between AGI grade and TEAS were analyzed. The 28-day Kaplan-Meier survival curves were generated for both groups. RESULTS: Finally, 133 patients were included, with 68 in the TEAS group and 65 in the control group. Baseline characteristics were comparable between the two groups. A comparison of the dynamic changes in intestinal biomarkers revealed that the I-FABP level in both groups decreased after treatment compared to pre-treatment, with a more pronounced reduction in the TEAS group. The least square mean difference (LS Mean difference) for the corrected I-FABP level between the two groups during the observation period was -0.23 μg/L [95% confidence interval (95%CI) was -0.45 to -0.01], which was statistically significant (P = 0.041). Additionally, a significant interaction with AGI was observed (P = 0.004). Post-treatment, D-lactic acid level decreased in both groups compared to pre-treatment, with a more significant reduction in the TEAS group. The LS Mean difference for the corrected D-lactic acid level was -0.08 mmol/L (95%CI was -0.11 to -0.05), which was statistically significant (P < 0.001), and the interaction with AGI was also significant (P = 0.005). There was no significant change in citrulline levels between the two groups before and after treatment. The LS Mean difference for the corrected citrulline level was -0.17 μmol/L (95%CI was -1.87 to 1.53), which was not statistically significant (P = 0.845), and no significant interaction with AGI was observed (P = 0.913). Comparison of EN tolerance parameters between the two groups revealed that the TEAS group had a longer total EN time (hours: 72±31 vs. 60±28) and higher total EN calories (kJ: 11 469.23±7 237.34 vs. 6 638.76±5 098.37), as well as a higher 70% target caloric attainment rate (52.9% vs. 32.3%) compared to the control group (all P < 0.05). The incidence of abdominal distension after EN was lower in the TEAS group than that in the control group (23.5% vs. 43.1%, P < 0.05), while the incidence of diarrhea after EN was higher in the TEAS group (22.1% vs. 7.7%, P < 0.05). There were no significantly differences in AGI grade reduction rate, post-EN vomiting/gastric retention rate, incidence of feeding interruption, and 28-day survival rate between the two groups. Furthermore, there were no significantly interaction between these observation measures and AGI. Kaplan-Meier survival analysis showed that there was no significantly difference in 28-day cumulative survival rate between the TEAS group and the control group [Log-Rank test: P = 0.501, hazard ratio (HR) = 0.81, 95%CI was 0.43-1.51), and there was no significantly interaction with AGI (P = 0.702). CONCLUSIONS The advantage of TEAS in the treatment of ICU patients with severe gastrointestinal function injury lies in its ability to reverse intestinal cell necrosis and promote the reconstruction of intestinal barrier function. Additionally, gastrointestinal tolerance is significantly improved, and both the duration and total calories of EN are increased. However, the limitation of TEAS therapy is that it does not promote the recovery of intestinal cell absorption and synthesis function in the target patients. Moreover, it may lead to nutrient solution overload due to improved gastrointestinal tolerance. Furthermore, TEAS does not appear to improve 28-day cumulative survival rate in the target patients.
Humans ; Prospective Studies ; Intensive Care Units ; Acupuncture Points ; Fatty Acid-Binding Proteins/metabolism* ; Transcutaneous Electric Nerve Stimulation ; Male ; Female ; Citrulline/metabolism* ; Lactic Acid/metabolism* ; Gastrointestinal Diseases/therapy* ; Middle Aged ; Enteral Nutrition ; Adult

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

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: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points