Dysregulated interactions between stress-sensitive neural circuits and immune signaling contribute to depression. We investigated whether the septohippocampal cholinergic pathway mediates the behavioral and neuroimmune effects of transcutaneous auricular vagus nerve stimulation (taVNS). Male mice were studied using chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) challenge models. Depression-related behaviors were assessed using the sucrose preference, forced swim, tail suspension, open field, and elevated plus maze tests. Cholinergic markers, hippocampal cytokines, microglial morphology, and α7 nicotinic acetylcholine receptor (α7nAChR) expression were examined by Western blotting and immunofluorescence. In a separate LPS cohort, hippocampal extracellular acetylcholine (ACh) was measured by microdialysis-HPLC during awake, freely moving recording. Cre-dependent excitatory DREADDs were used to activate medial septal ChAT neurons during taVNS treatment. CUMS increased medial septal ChAT expression and ChAT/c-Fos co-labeling, reduced hippocampal AChE and α7nAChR expression, and increased hippocampal TNF-α, IL-1β, IL-6, and microglial activation. Three weeks of taVNS improved depression-like behaviors and reversed these cholinergic and neuroimmune changes. In LPS-challenged mice, taVNS reduced hippocampal extracellular ACh and improved inflammation-associated anxiety/depression-related behavior. Chemogenetic activation of medial septal ChAT neurons attenuated the behavioral benefits of taVNS. These findings support septohippocampal cholinergic-microglial signaling as a neuroimmune mechanism through which taVNS improves depression-like behavior.

Background/Objectives: Migraine is a complex neurological headache disorder, and transcutaneous auricular vagus nerve stimulation (taVNS) can effectively relieve headache symptoms, but its mechanism of effect is still unclear. This study aimed to explore the regulatory effects of taVNS on the locus coeruleus (LC) and the norepinephrine (NE) system in migraine mice. Methods: C57/BL6 mice were randomly assigned to four experimental groups: the control group, model group, taVNS group, and sham taVNS group. A migraine model was established by administration of nitroglycerin. Headache behaviors were assessed using the orofacial stimulation test (OST) and the mouse grimace scale (MGS). Immunofluorescence staining was conducted to evaluate the expression of NE neurons in the LC, while Western blotting was used to determine the expression levels of α-2A adrenergic receptors in the spinal trigeminal nucleus caudalis (Sp5C). Additionally, fiber-optic recording was employed to monitor the real-time dynamics of NE release in Sp5C. Results: After taVNS intervention, the drinking time of OST in the model mice was significantly prolonged(p < 0.05), and facial expression scores were reduced (p < 0.05). TaVNS increased the number of NE neurons in the LC (p < 0.05), promoted the release of NE in Sp5C (p < 0.05), and upregulated the expression of α-2A adrenergic receptors in Sp5C (p < 0.05). Conclusions: The analgesic effects of taVNS are related to the activation of the LC-NE system and the inhibition of the decrease in Sp5C in migraine mice.

Introduction Lumbar back myofasciitis (LBM) is a common condition caused by cold exposure, lumbar injuries or poor posture, leading to aseptic inflammation, fibrosis and chronic pain. While acupuncture stimulation of trigger points is widely used, clinical evidence supporting its efficacy remains limited. This study aims to evaluate the effectiveness and safety of acupuncture stimulation of trigger points in the treatment of LBM and to explore the underlying analgesic mechanisms.Methods and analysis This single-centre randomised controlled trial will be conducted at Acupuncture and Moxibustion Hospital of China Academy of Chinese Medical Sciences. A total of 60 participants will be randomly assigned to either the experimental group or the control group in a 1:1 ratio. The primary outcome measure will be the Visual Analogue Scale for pain, while secondary outcomes will include pressure pain threshold, ultrasound, infrared thermography and Roland-Morris Disability Questionnaire.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences (Approval No. 2024XLW007-2). The findings of this study will be published in peer-reviewed journals. Prior to participation, all eligible participants will be given informed consent.Trial registration number ITMCTR2025000258.

ObjectivesThis study aims to investigate the mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a lipopolysaccharide (LPS)-induced acute inflammatory depression model in rats, focusing on the regulation of peripheral pro- and anti-inflammatory cytokines and the effects on the NF-κB signaling pathway in the prefrontal cortex.MethodsA depressive-like behavior model was established via intraperitoneal injection of LPS, and rats were randomly assigned to a normal group, a model group, and a taVNS intervention group. Behavioral assessments included the sucrose preference test (SPT), open field test (OFT), and elevated plus maze test (EPM) to evaluate depressive-like behaviors. Bio-Plex suspension array technology was used to detect inflammatory cytokine levels in serum, and Western blotting was performed to analyze the expression of NF-κB signaling pathway-related proteins in the prefrontal cortex.ResultsBehavioral tests demonstrated that LPS-induced rats exhibited significant depressive-like behaviors, including reduced sucrose preference, decreased activity levels in the open field, and restricted exploratory behavior in the elevated plus maze. taVNS intervention significantly alleviated these depressive-like behaviors. Serum analysis revealed that pro-inflammatory cytokines (e.g., IL-1β, TNF-α, MCP-1, IL-18, MIP-1α, and MIP-3α) were markedly elevated, while anti-inflammatory cytokines IL-4 and IL-10 were significantly reduced in the model group. taVNS intervention reversed these changes. Western blot analysis showed significant activation of the NF-κB signaling pathway in the model group, characterized by increased p-P65/P65 and p-IκB/IκB ratios and elevated TNF-α expression. taVNS intervention suppressed excessive activation of the NF-κB pathway by reducing p-P65 and TNF-α levels and stabilizing IκB expression.ConclusionsThis study demonstrates that taVNS significantly improves LPS-induced depressive-like behaviors by modulating peripheral pro- and anti-inflammatory cytokine levels and inhibiting the activation of the NF-κB signaling pathway in the prefrontal cortex. These findings highlight the critical role of taVNS in the regulation of the peripheral-central inflammation network and provide theoretical support for the development of taVNS-based non-invasive neuromodulation therapies.

OBJECTIVE:Our previous study found that astrocytes are involved in cumulative analgesia; however, the underlying mechanism remains unclear. The aim of this study was to further explore the potential role of astrocytes in the effects of electroacupuncture (EA) on neuropathic pain by focusing on the glutamate-glutamine cycle. METHODS:69 male Sprague-Dawley (SD) rats were randomly divided into a normal control group, untreated chronic constriction injury (CCI) model group and EA-treated model (CCI + EA) group. EA was applied bilaterally at ST36 and GB34. Pain thresholds were assessed using behavioral tests and thermal stimuli. We examined the co-expression of glutamate/aspartate transporter (GLAST) via immunofluorescence and measured the expression levels of GLAST, glutamate transporter (GLT)-1 and glutamine synthetase (GS) using Western blotting and polymerase chain reaction (PCR). Glutamate (Glu) and gamma-aminobutyric acid (GABA) levels were detected by high-performance liquid chromatography (HPLC). To validate the impact of GLAST/GLT-1 in the analgesic effect of EA, an additional 30 SD male rats were divided into groups receiving intrathecal saline, GLAST antagonist or GLT-1 antagonist alongside EA. RESULTS:Post-CCI, pain thresholds were decreased, GLAST expression was diminished, and spinal Glu levels were increased. EA treatment reversed these effects, improved pain thresholds and GLAST/GLT-1 expression in astrocytes, and reduced Glu levels. Antagonist administration negated the analgesic effects of EA. CONCLUSION:Repeated EA administration inhibited CCI-induced chronic neuropathic pain in rats, corresponding to a reversal of decreased expression of GLAST and GLT-1, which may have accelerated the clearance of Glu and thereby reduced its concentration. Regulation of the astroglial glutamate-glutamine cycle is a potential target of EA.

Depression is a serious disabling disease worldwide. Accumulating evidence supports that there is a close relationship between depression and inflammation, then inhibition of neuroinflammation may be another mechanism for the treatment of depression. Transcutaneous Auricular Vagus Stimulation(taVNS), as a non-invasive transcutaneous electrical stimulation, could effectively treat depression, but its mechanism is unclear. In this study, rats with depression-like behavior were induced by intraperitoneal injection of lipopolysaccharide (LPS). The rats were randomly divided to Control group, LPS group, taVNS + LPS group and the same as the α7 nicotinic acetylcholine chloride receptor(α7nAChR) (-/-) gene knockout rats. The expressions of tumor necrosis factor-alpha (TNF-ɑ) and phosphorylated-Janus kinase2(p-JAK2),phosphorylated-signal transducer and activator of transcription3(p-STAT3) in the hypothalamus, amygdala and hippocampus were detected by Western Blot. We observed that LPS significantly decreased the sucrose preference, the time of into the open arms in the elevated plus maze, and the number of corssing and reaing in the open field test. TaVNS treatment improves these depression-like behaviors, but taVNS is not effective in α7nAChR (-/-) gene knockout rats. The expression of TNF-ɑ signifciantly increased, and the expression of p-Jak2 and p-STAT3 markedly decreased in the hypothalamus and amygdala induced by LPS. TaVNS could significantly reverse the above-mentioned phenomena but had rare improvement effect for α7nAChR(-/-) rats. We conclude that the antidepressant effect of taVNS for LPS-induced depressive rats is related to α7nAchR/JAK2 signal pathway in the hypothalamus and amygdala.

Background and objectivesGrowing studies show that gut microbiota is closely associated with depression. Acupuncture treatment could regulate the gut microbiota of many diseases. Here, we aim to observe the effect of electroacupuncture (EA) on gut microbiota in rats that showed depressive-like behavior.Materials and methodsThe rats were randomly divided into normal group, chronic unpredictable mild stress model (CUMS) group, CUMS + electroacupuncture (EA) group, and CUMS + sham-electroacupuncture (Sham) group. The CUMS+EA rats were treated with EA stimulation at bilateral Zusanli (ST36) and Tianshu (ST25) acupoints for 2 weeks (0.7 mA, 2/100 Hz, 30 min/day). The rats in the sham EA group were treated with the same conditions without inserting needles and electrical stimulation. Behavioral tests were conducted by forced swimming test (FST), open field test (OFT), and sucrose preference test (SPT) to assess depression-like behavior in rats. The relative abundance of intestinal bacteria in rat feces was detected by 16S rRNA analysis. The expression of calcitonin-gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SST), and adrenocorticotropic hormone (ACTH) in serum was detected by ELISA kit, and VIP, CGRP, and SST in the colon were detected by qRT-PCR and Western blot.ResultsChronic unpredictable mild stress model rats exhibited depressive-like behaviors and had differential abundance vs. control rats. CUMS significantly decreased the relative abundance of Bifidobacterium and Streptococcus at the genus level, CGRP in plasma (p < 0.05), and significantly increased the intestine propulsion rate, the mRNA and protein expression of VIP, SST, and mRNA in the colon, and ATCH in plasma (p < 0.05). EA rats with microbial profiles were distinct from CUMS rats. EA markedly reduced the depressive-like behaviors, significantly increased the intestine propulsion rate, the relative abundance of Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level, Bifidobacterium and Streptococcus at the genus level, and VIP and CGRP in plasma (p < 0.05), and significantly decreased Firmicutes, the ratio of Firmicutes to Bacteroidetes at the phylum level, ACTH and SST in plasma, and SST mRNA in the colon (p < 0.05).ConclusionThe antidepressant effect of EA at ST36 and ST25 is related to regulating intestinal flora and the neurotransmitter system. Our study suggests that EA contributes to the improvement of depression, and gut microbiota may be one of the mechanisms of EA effect.

Under the guidance of traditional Chinese medicine theory, the clinical research of auricular acupoint stimulation in the treatment of migraine has gained a lot, and the curative efficacy is definite, but its mechanism remains unclear. In the present paper, we discussed the efficacy of auricular acupoint stimulation including "transcutaneous auricular vagus nerve stimulation" (taVNS) in the treatment of migraine in recent years. Through bibliometric analysis, we screened out top 10 auricular acupoints (Shenmen［TF4］, Pizhixia［AT4］, Jiaogan［AH6a］, Gan［CO12］, Yidan［CO11］, Neifenmi［CO18］, Shen［CO10］, Nie［AT2］, Zhen［AT3］ and E［AT1］) which were the most frequently used for migraine. Majority of these auricular acupoints just distributed in the region innervated by auricular vagus nerve. Thus, we thought that the analgesic effect of needling these auricular acupoints for migraine was produced by triggering the auricular vagus nerve, and concluded that the central mechanism underlying induction of analgesic effect by activating auricular vagus nerve may be achieved by activating the descending pain regulation pathway of the locus coeruleus nucleus and dorsal raphe nucleus. In addition, taVNS-induced 1) regulation of the activities of brain's default network and pain matrix, 2) activation of the cortical descending pain regulation pathway, and 3) inhibition of the neuroinflammatory response may also contribute to its ameliorating effect of migraine. This paper may provide ideas for the future research on the mechanism of auricular acupoint treatment of migraine.

BACKGROUND:Transcutaneous auricular vagus nerve stimulation (taVNS) is a vital neuromodulation for the treatment of depression, but its antidepressant molecular mechanism is unclear. The α7 nicotinic acetylcholine receptor (α7nAchR) is a key mediator of the vagus nerve that mediates its anti-inflammatory efficacy. Here, we investigated whether the antidepressant effect of taVNS in chronic unpredicted mild stress (CUMS)-exposed rats works through the α7nAchR/JAK2/STAT3/NF-κB pathway.METHODS:The depression model was established by CUMS for continuous 6 weeks in rats. From the 4th week of the experiment, CUMS-exposed rats were subjected to taVNS for 3 weeks. To clarify the role of α7nAchR in the antidepressant effect of taVNS, we used α7nAchR-/- gene knockout rats. The sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were used to evaluate depression-like behaviors of rats. Immunofluorescent staining was used to observe the morphology of microglia in the hypothalamus. Western blot was used to examine the protein expression of α7nAchR, p-JAK2, p-STAT3, IL-1β, NF-κB p65, and p-NF-κB p65 in the hypothalamus.RESULTS:Depression-like behaviors in CUMS-exposed rats were manifested by decreased SPT ratio, increased FST immobility time, decreased total distance, vertical movement score, and activity time of OFT. Hypothalamic neuroinflammation in CUMS-exposed rats was manifested by an amoebic-like activated state of microglia, downregulated expression of α7nAchR, p-JAK2, p-STAT3, and upregulated expression of NF-κB p65, p-NF-κB p65, and IL-1β. TaVNS could significantly reverse the above-mentioned phenomena, but had a poor improvement effect for CUMS-exposed α7nAchR-/- rats.CONCLUSION:The hypothalamic α7nAchR/JAK2/STAT3/NF-κB signaling pathway may play an important role in the antidepressant-like behavior of taVNS.

OBJECTIVE:To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the improvement of depressive-like behavior and the splenic α7 nicotinic acetylcholine receptor (α7nAchR) / Janus kinase 2 (JAK2 / signal transducer and activator of transcription 3 (STAT3) signaling pathway in lipopolysaccharide (LPS)-induced depressive-like behavior rats, so as to investigate the antidepressant mechanism of taVNS. METHODS:SD rats were randomly divided into SD control group, SD model group and SD taVNS group, and α7nAchR knockout rats were also randomly divided into α7 control group, α7 model group and α7 taVNS group, with 6 rats in each group. Rat model of depressive-like behavior was established by intraperitoneal injection of LPS (1 mg/kg). Rats in both SD taVNS and α7 taVNS groups received taVNS intervention once a day (2 Hz/15 Hz, 2 mA, 30 min) from 7 days before LPS injection to 2 days after LPS injection, respectively. The mean speed, activity time and side immobility time in the open field test were recorded after taVNS. The contents of interleukin 10 (IL-10) and chemokine (C-X-C motif) ligand 1 (CXCL1) in serum were detected by electrochemiluminescence multifactorial method. The splenic phosphorylated (p)-JAK2 and p-STAT3 protein expressions were detected by Western blot. RESULTS:Compared with their respective control groups, the mean speed and active time were reduced (P<0.01, P<0.05, P<0.001) and the side immobility time was increased (P<0.001) in the open field test, serum IL-10 and CXCL1 levels were up-regulated (P<0.01, P<0.05, P<0.001), and splenic p-JAK2 protein expressions were down-regulated (P<0.05, P<0.01) in SD and α7nAchR knockout rats, and splenic p-STAT3 protein expression were down-regulated (P<0.05) in SD rats after LPS injection. Following taVNS intervention and in comparison with the model group , the mean speed and active time were increased (P<0.01) and the side immobility time was decreased (P<0.001) in the open field test, serum IL-10 and CXCL1 levels down-regulated (P<0.05), while splenic p-JAK2 and p-STAT3 protein expressions were up-regulated (P<0.01, P<0.001) in the SD taVNS group rather than in the α7 taVNS group. Compared with SD taVNS group, the α7 taVNS group showed increased (P<0.001, P<0.05) side immobility time in the open field test and serum IL-10, decreased splenic p-JAK2 and p-STAT3 protein expressions (P<0.01, P<0.05). CONCLUSION:taVNS may exert anti-inflammatory effects through modulating the splenic α7nAchR/JAK2/STAT3 signaling pathway, thereby ameliorating LPS-induced depressive-like behavior in rats.

Transcutaneous auricular vagus nerve stimulation was recently reported to have a therapeutic potential for functional dyspepsia (FD). This study aimed to explore the integrative effects and mechanisms of auricular vagus nerve stimulation (aVNS) in a rodent model of FD. Methods: We evaluated the effects of aVNS on visceral hypersensitivity, gastric motility and open field test (OFT) activity in iodoacetamide (IA)-treated rats. The autonomic function was assessed; blood samples and tissues were collected and analyzed by an enzyme-linked immunosorbent assay and western blot. Vagotomy was performed to investigate the role of vagal efferent nerve. Results: aVNS reduced the electromyography response to gastric distension, improved gastric emptying and increased the horizontal and vertical motion scores of the OFT in IA-treated rats. The sympathovagal ratio was increased in IA-treated rats but normalized with aVNS. The serum cytokines TNF-α, IL-6, IL-1β and NF-κBp65 were increased in IA-treated rats and decreased with aVNS. The hypothalamus–pituitary–adrenal axis was hyperactive in IA-treated rats but inhibited by aVNS. The expression of duodenal desmoglein 2 and occludin were all decreased in IA-treated rats and increased with aVNS but not sham-aVNS. Vagotomy abolished the ameliorating effects of aVNS on gastric emptying, horizontal motions, serum TNF-α and duodenal NF-κBp65. Conclusion: aVNS improves gastric motility and gastric hypersensitivity probably by anti-inflammatory mechanisms via the vago-vagal pathways. A better understanding on the mechanisms of action involved with aVNS would lead to the optimization of the taVNS methodology and promote taVNS as a non-pharmacological alternative therapy for FD.

Background: There are 9.9 million new cases of dementia in the world every year. Short-term conversion rate from mild cognitive impairment (MCI) to dementia is between 20% and 40%, but long-term in 5-10 years ranges from 60% to 100%. It is particularly important to prevent or prolong the development of MCI into dementia. Both auriculotherapy and vagus nerve stimulation are effective on improving cognitive functions. However, there is no double blinded randomized clinical trial to support the effectiveness of transcutaneous electrical stimulation of auricular acupoints in patients with MCI.Methods: This randomized controlled trial involved patients with MCI, aged from 55 to 75 years old. Patients were randomly allocated to transcutaneous auricular vagus nerve stimulation (taVNS) group or sham taVNS group. In the taVNS group, two auricular acupoints were stimulated, including heart (concha, CO15) and kidney (CO10), which are in the distribution of vagus nerve. While in the sham taVNS group, two other auricular acupoints were stimulated, including elbow (scaphoid fossa, SF3) and shoulder (SF4,5), which are out of the distribution of vagus nerve. The primary outcome was the Montreal cognitive assessment-basic, MOCA-B. The secondary outcomes included auditory verbal learning test-HuaShan version (AVLT-H), shape trails test A&B (STT-A&B), animal fluence test (AFT), Boston naming test (BNT), Pittsburgh sleep quality index (PSQI), rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ), Epworth sleepiness scale (ESS) and functional activities questionnaire (FAQ). These outcome measures were taken at baseline, 24 weeks later.Results: After 24 weeks of intervention, the data of 52 patients were intended for analysis. After intervention, there was significant difference in the overall scores of MoCA-B between taVNS group and sham taVNS group (p = 0.033 < 0.05). In taVNS group, compared with before intervention, the overall scores of MOCA-B increased significantly after intervention (p < 0.001). As for N5 and N7, the two sub-indicators of AVLT-H, in taVNS group, compared with before intervention, both N5 and N7 increased significantly after intervention (both ps < 0.001). As for STTB, in taVNS group, compared with before intervention, STTB was significantly reduced after intervention (p = 0.016). For BNT, in taVNS group, compared with before intervention, BNT increased significantly after intervention (p < 0.001). In taVNS group, compared with before intervention, PSQI, RBDSQ, ESS and FAQ decreased significantly after intervention (p = 0.002, 0.025, <0.001, 0.006 respectively). 1 patient with a history of tympanic membrane perforation in taVNS group was reported with mild adverse reactions which disappeared a week after termination of taVNS. The intervention of taVNS is effective on increasing the overall scores of MoCA-B, N5 and N7.Conclusion: The clinical trial demonstrated that taVNS can improve cognitive performance in patients with MCI. This inexpensive, effective and innovative method can be recommended as a therapy for more patients with MCI in the prevention or prolonging of its development into dementia, but it is still required to be further investigated. Trial registration: http://www.chictr.org.cn. (ID: ChiCTR2000038868)(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

OBJECTIVE:To observe the effect of electroacupuncture (EA) on the expression of lumbar spinal κ-opioid receptor (KOR) and Toll-like receptor 4(TLR4) in microglia in neuropathic pain rats, so as to explore the role of cross-talk between KOR and TLK4 in EA-induced alleviation of chronic neuropathic pain.METHODS:Wistar male rats were randomized into control, model, EA and EA plus KOR inhibitor (EA+inhibitor) groups (n=18 in each group). The neuropathic pain model was established in rats by ligature of the right sciatic nerve. EA was applied at bilateral "Zusanli"(ST36) and "Yanglingquan"(GB34) for 30 min, once daily for 5 days. JDTic dihydrochloride (a KOR inhibitor) was administrated by intraperitoneal injection before EA intervention. The difference value of paw withdrawal thermal latency (PWLD) of the bilateral hind-limbs was used as the thermal pain reaction level. At the end of experiments, the rat's lumbar spinal cord (L2-L4) was taken for detecting the expression of CD68 mRNA (a marker of the activated microglia) and Iba-1 (a marker for the activated and resting microglia) immunoactivity, and dynorphin content, and KOR mRNA and TLR4 protein (in immunomagnetic microbead method separated microglia) by using fluorescence quantitative PCR, immunofluorescence, radioimmunoassay and Western blot, separately.RESULTS:Compared with the control group, a strong thermal hyperalgesia was induced, the expression levels of Iba-1 and CD68 mRNA in the spinal cord, TLR4 protein of the spinal microglia were significantly increased(P<0.01) in the model group. The microglia were characterized by somatic hypertrophy and thickened branches in the model group. After EA intervention, the PWLD, the expression of Iba-1, CD68 mRNA and TLR4 protein of the microglia were significantly decreased(P<0.05), while the content of spinal dynorphin and the expression of KOR mRNA of the microglia increased in the EA group relative to the model group(P<0.05). The hypertrophic microglia shrinked slightly in the EA group. After injection of KOR inhibitor, the PWLD and expression levels of Iba-1, CD68 mRNA and TLR4 protein were significantly increased(P<0.05), and the expression of KOR mRNA was significantly decreased(P<0.05) in the EA+inhibitor group in comparison with the EA group.CONCLUSION:The analgesia effect of EA may partly mediated by spinal microglial KOR and the activation of KOR of microglia may be a target for inhibition of microglial TLR4-induced pro-inflammatory signaling.

Objective Glial cells are involved in the analgesic effect of electroacupuncture (EA) in rats with chronic neurological pain. The objective of this study was to observe the role of neuronal–glial interaction and glutamate (Glu) transporters in EA-induced acute neck pain relief in rats. Materials and methods Male rats were placed into the following five groups: control, model, EA Futu (LI18), EA Hegu (LI4)-Neiguan (PC6), and EA Zusanli (ST36)-Yanglingquan (GB34). The incisional neck pain model was established by making a longitudinal incision along the midline of the neck. The thermal pain threshold (TPT) was measured using a radiation heat detector. The immunoactivities of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), neurokinin-1 receptor (NK-1R), Glu aspartate transporter (GLAST), and Glu transporter-1 (GLT-1) in the dorsal horns (DHs) of the cervico-spinal cord (C2–C5) were detected using immunofluorescence histochemistry. The expression levels of GFAP, Iba-1, GLAST, and GLT-1 mRNAs were determined using quantitative real-time polymerase chain reaction (PCR). Results The TPT and levels of mRNAs expression and immunoactivity of GLT-1 and GLAST were significantly decreased, and those of Iba-1 and GFAP were significantly increased in the model group than those of the control group (P < 0.05). The activated microgliacytes were gathered around the NK-1R positive neurons, and co-expression of NK-1R and astrocytes was observed in the model group. EA LI18 significantly increased the TPT and expression of GLAST and GLT-1 mRNAs (P < 0.05) and notably decreased the number of Iba-1 positive cells and Iba-l mRNA expression (P < 0.05), whereas GLAST and GLT-1 antagonists inhibited the analgesic effect of EA LI18. However, these effects, except for the downregulation of Iba-1 mRNA, were not observed in the EA ST36-GB34 group. Fewer NK-1R-positive neurons were visible in the spinal DHs in the EA LI18 group, and the co-expression of NK-1R and astrocytes was also lower than that in the three EA groups. Conclusion Electroacupuncture of LI18 had an analgesic effect in rats with neck incisions, which may be related to its functions in suppressing the neuronal–glial cell interaction through NK-1R and upregulating the expression of GLAST and GLT-1 in the spinal DHs.

Background: Evidences have shown the auricular vagus nerve stimulation (aVNS) is effective for functional dyspepsia (FD) recently. This study aimed to observe the mechanism of aVNS on facilitatory mediators of the inflammation in a rat model of functional dyspepsia. Methods: Thirty-six 5 d-old male Sprague Dawley rats were randomly divided into control groups (n = 12), model group (n = 12), aVNS group (n = 6) and sham-aVNS group (n = 6). Except for the control rats, all other rats were treated with iodoacetamide gavage. After the model was developed successfully, rats in aVNS group and sham-aVNS group received aVNS and sham-aVNS respectively, 30 min/1 time per day for 14 consecutive days. The control group and model group received no intervention. Gastric sensitivity after 1-week of intervention and gastric emptying after 2-week of intervention were adopted to assess the effect of aVNS. Brain-gut peptides, facilitatory mediators of the inflammation in serum were tested by ELISA, and α7 nicotinic acetylcholine receptor (α7-nAchR) in antrum tissue were tested by Immunohistochemistry to explore the mechanism of aVNS. Results: Compared with the control group, the gastric sensitivity was increased, gastric emptying decreased, and there was no structural damage in the gastric antrum in the model group. aVNS reduced visceral hypersensitivity and improved gastric emptying but not sham-aVNS. cholecystokinin, glucagon-like peptide-1, peptide, tumor necrosis factorα and interleukin 6 were all increased, while ghrelin and α7-nAchR decreased in model rats (P < 0.01 for all, compared with the control group). aVNS can normalize them. Conclusion: The aVNS can decrease the gastric sensitivity and increase gastric emptying, the mechanism was related to its regulation of brain-gut peptides and facilitatory mediators of the inflammation. The ameliorating effect was related to cholinergic mechanism.

Objectives After 20 years of development, there is a confusion in the nomenclature of transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN). We performed a systematic review of transcutaneous stimulation of ABVN in nomenclature. Materials and Methods A systematic search of the literature was carried out, using the bibliographic search engines PubMed. The search covered articles published up until June 11, 2020. We recorded the full nomenclature and abbreviated nomenclature same or similar to transcutaneous stimulation of ABVN in the selected eligible studies, as well as the time and author information of this nomenclature. Results From 261 studies, 67 full nomenclatures and 27 abbreviated nomenclatures were finally screened out, transcutaneous vagus nerve stimulation and tVNS are the most common nomenclature, accounting for 38.38% and 42.06%, respectively. In a total of 97 combinations of full nomenclatures and abbreviations, the most commonly used nomenclature for the combination of transcutaneous vagus nerve stimulation and tVNS, accounting for 30.28%. Interestingly, the combination of full nomenclatures and abbreviations is not always a one-to-one relationship, there are ten abbreviated nomenclatures corresponding to transcutaneous vagus nerve stimulation, and five full nomenclatures corresponding to tVNS. In addition, based on the analysis of the usage habits of nomenclature in 21 teams, it is found that only three teams have fixed habits, while other different teams or the same team do not always use the same nomenclature in their paper. Conclusions The phenomenon of confusion in the nomenclature of transcutaneous stimulation of ABVN is obvious and shows a trend of diversity. The nomenclature of transcutaneous stimulation of ABVN needs to become more standardized in the future.

The hypothalamus–pituitary–adrenal axis is the most important endocrine system to control irritability response. Functional dyspepsia (FD) is closely related to irritability. This study aimed to preliminarily explore the corticotropin-releasing factor (CRF) mechanism of auricular vagus nerve stimulation (aVNS) for FD model rats. Sprague–Dawley adult male rats were randomly divided into normal group, model group, aVNS group, and sham-aVNS group. Except for the normal rats, all other rats were induced into the FD model through tail-clamping stimulation for 3 weeks. Once the rat model was developed successfully, rats in the aVNS group and sham-aVNS group were intervened with aVNS or sham-aVNS for 2 weeks. No intervention was given to rats in the normal and model groups. The effect of aVNS was assessed. The expressions of hippocampal corticotropin-releasing hormone receptor 1 (CRHR1), hypothalamus CRF, adrenocorticotropic hormone (ACTH), and corticosterone in serum were assessed. 1. Compared with normal rats, model-developing rats showed FD-like behavior. 2. Compared with model rats, rats in the aVNS group showed an improved general condition score and gastric motility, and increased horizontal and vertical motion scores. 3. The release of corticosterone, ACTH in serum, and CRF in the hypothalamus all increased in model rats but decreased with aVNS instead of sham-aVNS. 4. The expression of hippocampus CRHR1 was lower in model rats but higher in the aVNS group. aVNS ameliorates gastric motility and improves the mental state in the FD-like rat, probably via inhibiting the CRF pathway.

Objective: Transcutaneous auricular vagus nerve stimulation (taVNS) can relieve the symptoms of functional dyspepsia (FD) and improve the quality of life of patients, however, the mechanism underlying this effect remains unclear. Therefore, this study aimed to investigate the effects of taVNS on the expression of intestinal mucosal ligandins. Methods: This study was conducted on 24 specific Spathogen-free Sprague-Dawley rats (12 males and 12 females). The rat model of FD was established by tail-clip stimulation. After FD was established successfully, all rats were randomized to either the normal group (n = 6), model group (n = 6), taVNS group (n = 6), or sham-taVNS group (n = 6). After two weeks of the respective intervention, the score of their general conditions, 3 h food intake, gastric emptying rate, and the histology of gastric antrum tissues were observed to evaluate modeling success, and then the effect of taVNS was evaluated. Western blotting was used to assess the expression of the tight junction ligandins -ZO-1 and occludin-and the adhesion ligandin-beta-catenin-in the duodenum. The effect of taVNs on the expression of intestinal mucosal barrier ligandins-ZO-1, occludin, and beta-catenin-in FD rats was preliminarily investigated. Results: When the model-induced period was finished, the manifestations of FD in the model group rats were mental exhaustion, reduced activities, decreased score of the general conditions, and decreased 3 h food intake, compared to the normal group rats. In addition, minimal eosinophil infiltration, without any mucosal erosion or ulcer, was observed in the gastric antrum mucosa. At the end of the study, the mental state of the FD rats improved, and their activities and gastric emptying rate increased in the taVNS group rats. Compared to the normal rats, the duodenal mucosa had less expression of the tight junction ligandins ZO-1 and occludin, but beta-catenin expression remained unchangedin the model rats. The expression of the tight junction ligandins ZO-1 and occludin were increased in the duodenal mucosa of model rats after the taVNS intervention. Conclusion: TaVNS can improve the gastric motility and mental state of rats with FD. It may play a therapeutic role by improving the expression of the tight junction ligandin ZO-1 and occludin in the duodenal mucosa, while also repairing the duodenal mucosal barrier. (C) 2021 Published by Elsevier B.V. on behalf of World Journal of Acupuncture Moxibustion House.