The spinoparabrachial tract is a major ascending pathway that transmits nociceptive signals from the spinal cord to the brain, but whether electroacupuncture (EA) relieves pain-anxiety comorbidity by modulating this pathway remains unclear. Here, we investigated the effects of EA on mechanical allodynia and anxiety-like behaviors in Complete Freund's adjuvant (CFA)-induced inflammatory pain mice using von Frey testing, the open field test, and the elevated plus maze, combined with chemogenetic manipulation of glutamatergic projections from the spinal dorsal horn (SDH) to the lateral parabrachial nucleus (LPBN). EA attenuated CFA-induced mechanical allodynia and anxiety-like behaviors and reduced c-Fos expression in both the SDH and LPBN. Chemogenetic inhibition of LPBN glutamatergic neurons mimicked the analgesic and anxiolytic effects of EA, whereas their activation abolished these effects. Activation of either ipsilateral or contralateral SDH→LPBN glutamatergic projections induced pain- and anxiety-like phenotypes that depended on intact LPBN glutamatergic output. Moreover, selective activation of spinoparabrachial glutamatergic terminals was sufficient to block the therapeutic efficacy of EA. These findings indicate that EA alleviates CFA-induced pain-anxiety comorbidity by inhibiting the SDH-LPBN glutamatergic circuit, identifying a key ascending pathway through which peripheral EA signals modulate central pain and affective processing.

OBJECTIVE:This study investigated the role of the cannabinoid receptor type 2 (CB2R) in the spinal cord dorsal horn (SCDH) using a spared nerve injury (SNI) model of neuropathic pain (NP). The aim was to clarify the analgesic effects of different electroacupuncture (EA) frequencies in SNI rats and to explore whether the higher frequency exerts analgesic effects by modulating the CB2R signaling pathway. METHODS:An SNI rat model was initially established. Mechanical allodynia was assessed using the paw withdrawal threshold (PWT), and motor function was assessed using a gait analysis system. Expression levels of CB2R, phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK), cluster of differentiation 11b (CD11b), ionized calcium-binding adapter molecule 1 (Iba1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were quantified via immunofluorescence staining and Western blot analysis. The functional role of the CB2R/p38 MAPK pathway was further investigated through intrathecal administration of the CB2R agonist AM1241 and the p38 MAPK inhibitor SB203580. The analgesic effects of low-frequency (2 Hz) and high-frequency (100 Hz) EA were observed in SNI rats, and the modulatory effect of the superior frequency (2 Hz EA) on this pathway was explored. The CB2R antagonist AM630 was co-administered with low-frequency EA to evaluate its impact on pathway activity. RESULTS:CB2R and p-p38 MAPK expression increased after SNI and they were mainly expressed in microglia. The SNI group exhibited a substantial increase in Iba1 and CD11b staining intensity, indicating robust microglial activation, along with elevated levels of the pro-inflammatory cytokine IL-6. Intrathecal administration of either the CB2R agonist AM1241 or the p-p38 MAPK inhibitor SB203580 increased the PWT, inhibited microglial activation and decreased the release of inflammatory cytokines in the SCDH. Both low-frequency EA and high-frequency EA were effective in alleviating pain induced by SNI. Low-frequency EA was significantly more effective than high-frequency EA in improving PWT. Low-frequency EA improves SNI-induced gait disturbances. Low-frequency EA ameliorated hyperalgesia in SNI rats by enhancing CB2R expression and suppressing p-p38 MAPK activation. AM630 reversed this analgesic effect. Moreover, EA attenuated microglial activation and lowered the levels of pro-inflammatory cytokines, specifically TNF-α and IL-6, in the SCDH. It also suppressed the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT). Notably, CB2R antagonism abolished all these effects. CONCLUSION:CB2R participates in SNI-induced NP by activating the p38 MAPK pathway. Low-frequency EA shows superior efficacy compared with high-frequency EA and alleviates NP through CB2R-mediated suppression of the p38 MAPK and PI3K/AKT signaling in the SCDH. Please cite this article as: Wei ZY, Zhang JJ, Lin C, Li SY, Kang YR, Liang JQ, Liu ZQ, He XF, Shao XM, Fang JQ, Jiang YL. Low-Frequency electroacupuncture alleviates neuropathic pain via cannabinoid receptor type 2 signaling in the spinal cord dorsal horn. J Integr Med. 2026; Epub ahead of print.

Background Chronic pain is frequently accompanied by cognitive dysfunction, while whether pain-related memory impairment depends on task difficulty remains unclear. According to the limited cognitive resource hypothesis, persistent pain may consume finite neural processing capacity and thereby impair cognitive performance mainly under high cognitive demand. Electroacupuncture (EA) alleviates neuropathic pain and may improve cognitive function, but its effect on task-dependent memory deficits associated with chronic neuropathic pain remains insufficiently defined. This study investigated whether spared nerve injury (SNI)-induced neuropathic pain selectively impairs memory under high cognitive demand and whether repeated EA reverses these deficits. Results SNI induced robust mechanical hypersensitivity in rats but did not produce detectable impairments in novel object recognition (NOR) or post-NOR novel object location (NOL) performance under low-difficulty conditions. While under high-difficulty conditions, SNI rats showed impaired long-term object recognition memory, whereas post-NOR location memory remained unaffected. When object novelty and spatial relocation were combined in a higher-demand NOR + NOL task, SNI rats exhibited deficits in both object recognition and object-location memory. Repeated 2-Hz EA at ST36 and SP6 attenuated mechanical hypersensitivity and restored impaired performance in high-demand memory tasks. Immunofluorescence analysis showed that SNI reduced the percentage of CaMKII/c-Fos double-positive neurons among CaMKII-positive neurons in the rostral anterior cingulate cortex (rACC), whereas EA increased CaMKII/c-Fos co-localization to a level comparable with that in sham-operated rats. Conclusions Chronic neuropathic pain selectively disrupts long-term memory under high cognitive demand while producing no detectable impairment under lower task demand, supporting a resource-competition model of pain-cognition interaction. Repeated EA alleviates mechanical hypersensitivity and reverses task-dependent memory deficits, and these behavioral effects are associated with increased CaMKII/c-Fos co-localization in rACC CaMKII-positive neurons. These findings suggest that EA may represent a superior efficacy for chronic pain-associated cognitive dysfunction by increasing the CaMKII-positive neuronal activation in the rACC.

Objective To observe the efficacy of different needle manipulation techniques at myofascial trigger points(MTrPs)in treating myofascial pain syndrome(MPS)and to determine which technique is more advantageous.Methods A total of 108 MPS patients were randomly divided into a twisting group(36 cases,with 5 dropouts),a lifting-thrusting group(36 cases,with 3 dropouts),and a non-manipulation group(36 cases,with 6 dropouts).The twisting group and lifting-thrusting group received twisting or lifting-thrusting techniques for 1 min at MTrPs,respectively,while the non-manipulation group retained the needles without manipulation for 1 min.Treatments were administered every other day,totaling 3 sessions.Before and after the first treatment and after the final treatment,patients completed the short-form McGill pain questionnaire(SF-MPQ),including the pain rating index(PRI),visual analog scale(VAS),and present pain intensity(PPI)scores.Young's modulus values at MTrPs were measured using ultrasound elastography before and after treatment.The Massachusetts acupuncture sensation scale(MASS)was used during each treatment to record the types and intensity of needling sensations.Clinical efficacy was evaluated after the final treatment.Results After the final treatment,SF-MPQ,PRI,VAS,PPI scores,and Young's modulus values decreased(P<0.05)in all the 3 groups compared to pretreatment.After treatment,the twisting and lifting-thrusting groups showed greater reductions in SF-MPQ,PRI,PPI scores,and Young's modulus values(P<0.05)compared to the non-manipulation group,while the lifting-thrusting group had lower VAS scores(P<0.05)than the non-manipulation group.The lifting-thrusting group exhibited higher frequencies of twitching sensations and greater distension intensity(P<0.05)than the non-manipulation group.Both the twisting and lifting-thrusting groups had higher mean needling sensation intensity of twitching sensations,needle grasp(practitioner's sense of tightness),and MASS values(P<0.05)than the non-manipulation group.The total effective rates were 80.65%(25/31)in the twisting group,84.85%(28/33)in the lifting-thrusting group,and 66.67%(20/30)in the non-manipulation group,with the lifting-thrusting group showing higher efficacy than the non-manipulation group(P<0.05).Pain relief was positively correlated with the occurrence of twitching sensations and needle grasp(P<0.01),as well as with the intensity of distension,twitching sensations,MASS values,and needle grasp(P<0.01).Conclusion Both twisting and lifting-thrusting techniques at MTrPs yield better clinical outcomes for MPS than non-manipulation,with the lifting-thrusting technique demonstrating superior overall efficacy.The lifting-thrusting technique is more advantageous than twisting in eliciting twitching sensations during MTrP acupuncture.

BackgroundThe prevalence of adolescent major depressive disorder (MDD) is rising; however, diagnosis relies on subjective measures due to a lack of objective biomarkers. This study explored infrared thermography (IRT) as a non-invasive tool to quantify thermal radiation characteristics of acupoints in adolescents with MDD. The objective was to establish diagnostic models based on acupoint temperature-derived biomarkers.MethodsA prospective, multi-center observational study enrolled 108 participants (65 adolescents with MDD and 43 healthy controls [HCs]). We first examined correlations between acupoint temperatures and depression severity using Pearson analysis. Multiple linear and binary logistic regression models were developed to diagnose MDD and assess severity. The diagnostic model for MDD was visualized as a nomogram and validated using Receiver Operating Characteristic (ROC) curves, Hosmer-Lemeshow tests, calibration plots, and decision curve analysis (DCA). Internal validation was performed using the bootstrap method.ResultsAmong 27 acupoints analyzed, adolescents with MDD exhibited altered acupoint temperatures at Taiyang (EX-HN5), Quchi (LI11), Yanggu (SI5), and Waiqiu (GB36). Subsequent Pearson correlation analysis revealed negative correlations between the infrared relative temperatures of Taiyang (EX-HN5), Quchi (LI11), and Waiqiu (GB36) and depression severity (P = 0.001, r = -0.319; P = 0.022, r = -0.229; P = 0.001, r = -0.325) and a weak positive correlation between the infrared relative temperature of Yanggu (SI5) and depression severity (P = 0.043, r = 0.202). Building on these findings, two diagnostic models were developed: a linear regression model for depression severity of adolescents (Y = 52.25-9.52*TEX-HN5-13.07*TGB36) and a logistic regression model for adolescents with MDD diagnosis (P = ex/(1+ex), x = 0.22-1.14*TEX-HN5+0.45*TSI5-2.19*TGB36). The nomogram-based model demonstrated good calibration (Hosmer-Lemeshow P = 0.855), discrimination (AUC = 0.785, 95%CI: 0.693 - 0.876), and clinical utility. Internal validation using the bootstrap method produced a C-index of 0.752 (95% CI: 0.617 - 0.877), further confirming the model’s robustness.ConclusionsIn conclusion, acupoint temperature-based models show promising efficacy for the objective and non-invasive diagnosis and severity quantification of adolescents with MDD, offering valuable tools for early clinical intervention. Future studies should validate these findings across diverse populations and integrate multi-modal biomarkers to enhance diagnostic precision.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT06750640.

BACKGROUND:The analgesic effects of multiple electroacupuncture (EA) sessions and single EA sessions differ significantly in pain management. Area 24b (A24b) of the anterior cingulate cortex (ACC) is crucial in pain processing. EA relieves pain by targeting and modulating the neuronal activity within this subregion. However, whether the cumulative effect of EA antinociception is connected to A24b mechanisms has remained unclear. METHODS:In our study, we used the Complete Freund's Adjuvant (CFA) model to induce inflammatory pain and the Spared Nerve Injury (SNI) model to induce neuropathic pain, and adult male C57BL/6, FosTRAP, and FosTRAP:Ai9 mice were used as experimental subjects to investigate the cumulative effect of EA antinociception and whether multiple EA sessions and a single EA session regulate different neuronal populations in the A24b. RESULTS:We observed that EA effectively alleviated pain in mice, with three EA sessions yielding superior analgesic effects compared to a single session. Using chemical genetics combined with FosCreER technology to activate EA-TRAPed cells in the A24b, we found that pain relief was more pronounced with three EA sessions. Moreover, chemogenetic inhibition of EA-TRAPed cells in the A24b reversed the analgesic effects of a single EA session but not those of three EA sessions. Fluorescent in situ hybridization results indicated that three EA sessions significantly increased the number of GABAergic neurons in the A24b compared with a single session. Additionally, retrograde tracing revealed that the A24b circuit that monosynaptically innervates EA-TRAPed cells included projections from the central lateral nucleus (CL), lateral mediodorsal thalamic nucleus (MDL), lateral habenula (LHb), dorsal raphe nucleus (DR), caudal linear nucleus of the raphe (CLi), dorsal tuberomamillary nucleus (DTM), periventricular hypothalamic nucleus (Pe) and hippocampal fields CA1, CA2, and CA3. These findings suggest that multiple EA sessions and single EA sessions activated different neuronal populations in the A24b. The enhanced analgesic effect of multiple EA sessions may be attributed to an increase in the proportion of GABAergic neurons within the A24b. CONCLUSIONS:Multiple and single EA sessions recruit distinct neuronal populations in A24b, with the stronger analgesic effect of repeated EA linked to a higher proportion of GABAergic neurons in this region.

The ventrolateral preoptic nucleus (VLPO) of the anterior hypothalamus is a major sleep-promoting region and a key component of the networks governing sleep–wake regulation. Rather than acting as a unitary “sleep center,” the VLPO is increasingly understood as a molecularly and functionally heterogeneous ensemble embedded within distributed preoptic, hypothalamic, and brainstem circuits. In this review, we revisit classical lesion, c-Fos, and electrophysiological evidence alongside recent advances in single-cell transcriptomics, projection-specific circuit mapping, and in vivo functional interrogation. We summarize how the core and extended VLPO and their constituent neuronal populations—including GABA/galanin co-expressing neurons, non-galanin GABAergic neurons, and glutamatergic neurons—contribute differentially to non-rapid eye movement (NREM) sleep, rapid eye movement (REM)-associated processes, state transitions, thermoregulation, and metabolic integration. We further examine how circadian timing, homeostatic sleep pressure, metabolic signals, and thermal inputs converge on VLPO-related circuitry through interactions with neighboring preoptic populations and broader hypothalamic–brainstem arousal systems. This network perspective helps reconcile classical VLPO-centered models with emerging evidence for distributed and partially redundant control of sleep–wake states. We also highlight unresolved issues, including the molecular definition of VLPO subregions, functional overlap with adjacent preoptic nuclei, inconsistencies across experimental approaches, and the challenge of translating rodent circuit findings to humans. Taken together, current evidence supports viewing the VLPO not as an isolated sleep center, but as a multisystem integrator within distributed sleep-regulatory networks.

Background:Acupuncture has been increasingly applied as an adjunctive treatment for major depressive disorder (MDD), yet its central neurobiological mechanisms remain insufficiently understood. Cerebral blood flow (CBF) and functional connectivity strength (FCS) provide complementary perspectives on regional metabolic activity and large-scale functional integration, and their coupling may reflect neurovascular coordination relevant to depression. Methods:Twenty patients with MDD and twenty matched healthy controls (HC) underwent resting-state MRI. Patients received intradermal acupuncture (IA) and were scanned before and immediately after stimulation, while healthy controls were scanned once. Voxel-wise analyses of CBF, FCS, and their ratio (CBF/FCS) were performed to characterize acupuncture-related changes in neurovascular coupling. Group comparisons and pre-post acupuncture effects were assessed at the whole gray matter level. Results:Acupuncture induced significant alterations in CBF/FCS coupling across widespread brain regions, including the bilateral precuneus, postcentral gyrus, superior temporal pole, superior frontal gyrus, occipital cortex, and cerebellum. These regions are primarily involved in sensorimotor processing, cognitive control, and emotional regulation. Overall, IA was associated with an immediate increase in CBF/FCS coupling, suggesting enhanced coordination between cerebral perfusion and functional network integration. Conclusion:This study provides evidence that intradermal acupuncture modulates neurovascular coupling in patients with MDD, offering neuroimaging-based insights into its antidepressant mechanisms. The findings support the notion that acupuncture may facilitate more efficient brain function by optimizing the balance between neural activity and metabolic supply.

OBJECTIVE:The aim of the study was to observe the changes in phosphorylated caveolin-1 (p-Cav-1) expression in the dorsal root ganglion (DRG) of rats with diabetic neuropathic pain (DNP) and to explore the interventional effect of electroacupuncture on Cav-1. METHODS:In experiment 1, DNP was induced by intraperitoneal streptozotocin (STZ). Fasting blood glucose (FBG), body weight, and paw withdrawal latency (PWL) to thermal stimuli were measured at baseline and on days 7, 14, and 21 post-STZ. p-Cav-1-positive cells in L4-L6 DRG were detected by immunofluorescence. In experiment 2, rats were divided into normal, STZ, and STZ+siRNA groups. From days 15-21, cav-1-siRNA or blank liposomes were administered intrathecally. FBG, body weight, and PWL were measured. In experiment 3, rats were divided into normal, STZ, and STZ+electroacupuncture groups. From days 15-21, electroacupuncture (2 Hz, 30 min daily) was applied at ST36 and BL60. The above indicators and p-Cav-1 expression were detected. RESULTS:In experiment 1, compared with the normal group, the DNP group showed increased FBG, decreased body weight (D7-D21), and shortened PWL (D14, D21). The number of p-Cav-1-positive neurons in DRG significantly increased in L4-L5 (D7) and L4-L6 (D14, D21). In experiment 2, after siRNA intervention, the PWL of the STZ + siRNA group was significantly prolonged compared with the DNP group. In experiment 3, after electroacupuncture intervention, the PWL of the STZ + electroacupuncture group was significantly prolonged compared with the DNP group (D21), and the expression of p-Cav-1-positive cells in DRG was significantly decreased compared with the STZ group. CONCLUSION:Upregulation of p-Cav-1 expression in DRG is involved in the development of DNP. Electroacupuncture can effectively alleviate hyperalgesia in DNP rats, and its mechanism may be related to the inhibition of p-Cav-1 expression in DRG.

BACKGROUND:The efficacy of nonpharmacological therapies for patients with gastroesophageal reflux disease (GERD) has been progressively proved. However, the specific differences in effectiveness among various nonpharmacological interventions and their combinations with pharmacological interventions remain unclear, and the optimal intervention strategy has yet to be conclusively determined. METHODS:Systematic searches were conducted in PubMed, Web of Science, Embase, Cochrane, and CNKI from inception to November 6, 2024. A network meta-analysis was conducted using a random effects consistency model within a Bayesian framework with lower esophageal sphincter (LES) pressure as the primary outcome indicator. RESULT:Thirty-three studies involving 10 nonpharmacological interventions were included. Acupoint stimulation with traditional Chinese medicine (TCM) (SMD=5.83, 95% CI: 1.23 to 10.16), and breathing training with conventional Western medicine (CWM) (SMD=3.88, 95% CI: 0.45 to 7.52) significantly improved LES pressure and reduced esophageal acid exposure time (AET) (SMD=-5.01 to -3.32). In terms of safety, acupoint stimulation with TCM (logOR=-2.51, 95% CI: -5.91 to -0.19) exhibited a significant advantage over CWM. However, acupoint stimulation combined with TCM and breathing training with CWM did not demonstrate a significant improvement in GERD health-related quality of life questionnaire (HRQL) scores. CONCLUSION:Acupoint stimulation combined with TCM and breathing training with CWM, when compared with CWM and other nonpharmacological interventions, is considered a potential adjunctive therapeutic approach for GERD, demonstrating both efficacy and safety. However, methodological limitations necessitate cautious interpretation of results.

Pei-qi Li,&ast; Mei Huang,&ast; Xiao-mei Shao The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-mei Shao, The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China, Email 13185097375@163.com

Multiple lines of evidence, including clinical and preclinical, associate depression with dysregulated glutamate homeostasis in the central nervous system. The astrocyte-enriched cysteine/glutamate antiporter, xCT, plays a pivotal role in maintaining this homeostasis, and its dysfunction is linked to depressive-like behaviors induced by chronic stress. However, the exact mechanism through which chronic stress results in xCT dysfunction remains poorly understood. In this study, we demonstrate that chronic social defeat stress (CSDS) downregulates xCT expression in the prelimbic cortex (PL), a key cortical region involved in the aetiology of depression, through astroglial kappa opioid receptor (KOR)-dependent, p38 MAPK-mediated upregulation of miR-3084-5p expression, which in turn downregulates xCT expression by inhibiting mRNA that encodes xCT. Knockdown of KORs as well as overexpression of xCT in the PL astrocytes significantly attenuates CSDS-induced depressive-like behaviors. Blockade of p38 MAPK activity or suppression of miR-3084-5p function restores xCT expression and alleviates depressive-like behaviors. Together, this study reveals a novel mechanism by which chronic stress deregulates glutamate homeostasis and consequently results in depression.

Purpose:Neck-type cervical spondylosis (NTCS) is the most common subtype of cervical spondylosis. Acupuncture is frequently employed in the clinical management of NTCS. According to the traditional Chinese medicine theory of acupoint sensitization, acupoints represent both highly sensitive reactive sites during pathological states and the principal loci for therapeutic stimulation via acupuncture. Stimulating strongly sensitive points has been shown to be effective in treating disease and may enhance clinical efficacy. This study aims to investigate the clinical effect and safety of acupuncture at sensitized acupoints (SA) in alleviating symptoms in patients with NTCS, based on the specificity of acupoint sensitization. Patients and Methods:This is a single-center, prospective, patient- and assessor-blinded, randomized, sham-controlled trial involving patients diagnosed with NTCS. Participants will be randomly assigned in a 1:1 ratio to two groups: the SA group and sham acupuncture (SHA) group. All participants will be treated with acupuncture three times during the first week, followed by a subsequent assessment scheduled in week five. The primary outcome is the alteration in the intensity of neck pain, assessed with the visual analogue scale. Secondary outcomes include changes in the neck disability index, range of motion, the 12-item short form health survey, cervical musculoskeletal ultrasound findings, and pressure pain threshold values. The intention-to-treat analysis will be applied for statistics. Conclusion:This trial will be the first randomized controlled trial to investigate the therapeutic efficacy and safety profile of acupuncture SA in the treatment of NTCS. It is also the first trial to combine subjective and objective outcome measures to comprehensively evaluate acupuncture's curative effect on NTCS management. The findings may provide evidence supporting acupuncture as an effective treatment option for NTCS and offer insights into its underlying biological mechanisms. Trial Registration:ClinicalTrials.gov (https://clinicaltrials.gov/), identifier: NCT06847945.

BACKGROUND:Multiple non-pharmacological and nonsurgical interventions have demonstrated efficacy in improving abdominal obesity. However, the optimal intervention remains uncertain. This study aimed to assess the relative effectiveness and safety of these interventions in reducing waist circumference, waist-to-hip ratio, waist-to-height ratio (WHtR), body mass index (BMI), and body weight among adults with abdominal obesity. METHODS:Eight databases, including PubMed, Web of Science, Excerpta Medica Database, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database, and China Science and Technology Journal Database, were systematically searched from inception to February 20, 2025 for published randomized controlled trials (RCTs). Methodological rigor was assessed through the Cochrane Risk of Bias tool. After establishing direct evidence through pairwise comparisons in STATA 17.0, we implemented a Bayesian hierarchical model in R 4.4.2 to generate treatment rankings for abdominal obesity interventions. RESULTS:Thirty RCTs (involving 3334 participants) were included in the meta-analysis. Among the interventions, acupoint catgut embedding (ACE) combined with electroacupuncture (EA), ACE combined with manual acupuncture, ACE alone, high-intensity interval training, and warming needle were the 5 most effective interventions for reducing waist circumference in patients with abdominal obesity. For improving waist-to-hip ratio, the top interventions included low-intensity steady-state training, ACE, EA, high-intensity continuous training, and high-intensity continuous training combined with a calorie-restricted diet, while ACE was the most effective intervention for reducing waist-to-height ratio. In terms of BMI and body weight reduction, ACE combined with EA, warming needle, and ACE ranked as the top 3 effective interventions. CONCLUSION:ACE combined with EA achieved the greatest waist circumference reductions among non-pharmacological and nonsurgical interventions for adults with abdominal obesity, with observed benefits extending to secondary outcomes including BMI and body weight. This integrated therapy exhibits considerable potential for clinical management of abdominal obesity. Future large-scale, multicenter RCTs involving diverse populations are warranted to further validate and refine its application.

Complex regional pain syndrome type I (CRPS-I) develops after an initial injury. It causes prolonged pain that persists beyond the usual expected time for tissue healing. Mechanisms underlying pain chronicity of CRPS-I remain unknown. Here, we identified the presence of long-lasting infiltration of macrophages in local dorsal root ganglia (DRG) of a rat model of CRPS-I. We demonstrate that regenerating islet-derived 3β (Reg3β) is specifically produced by DRG neurons upon model establishment and functions as an important signaling molecule to drive proinflammatory macrophage infiltration in local DRG. Infiltrated macrophages produce TNF-α, which causes hyperexcitability of nociceptive DRG neurons and reciprocally promotes Reg3β overexpression and secretion from DRG neurons to recruit more macrophages. Our work reveals a positive feedback signaling conveyed by neuronal Reg3β/macrophage TNF-α that contributes to neuroinflammation in DRG, resulting in persistent pain in a rat model of CRPS-I. This finding provides insights into the neuroimmune interaction in local DRG that contributes to pain chronicity of CRPS-I.

Evidence indicates that the interplay between pain and anxiety poses clinical challenges for the evaluation and management of chronic pain, yet effective therapies for these comorbidities are limited. This study aimed to elucidate the effects and mechanisms of electroacupuncture (EA) on pain-anxiety comorbidities. Mice injected with Complete Freund's adjuvant (CFA) in the ipsilateral hind paw developed persistent inflammatory pain and anxiety-like behaviors, as assessed by the von Frey, open field, elevated plus maze, and novelty-suppressed feeding tests. EA was administered 12-17d after CFA injection with once daily. rAAV virus and chemogenetics were used to manipulate parvalbumin (PV) interneurons and astrocytes excitation in the anterior cingulate cortex (ACC). Immunofluorescence, morphological analysis, patch clamp and in vivo fiber Ca2+ imaging were used to examine the activation of PV interneurons and astrocytes. The effect of EPCPX (antagonist of A1R) and chemogenetics activated astrocytes on EA analgesia were observed in a subset of mice prior to EA. EA administration alleviated pain and anxiety-like behaviors in CFA mice, activated PV interneurons, and inhibited astrocytes activation in the ACC. Furthermore, both PV interneurons activation and astrocyte inhibition in the ACC elicited effects similar to those elicited by EA on pain and anxiety. Chemogenetic activation of ACC astrocytes reversed the effects of EA. Additionally, astrocyte activation in the ACC suppressed PV interneurons and induced pain-anxiety like behaviors in mice. Adenosine A1 receptors, crucial for mediating the interaction between astrocytes and PV interneurons in the ACC, were also found to be involved in the effects of EA on pain-anxiety comorbidity. These findings reveal that EA alleviates the pain and anxiety comorbidity through a potential mechanism involving the activation of PV interneurons, which are modulated by the inhibition of astrocytes in the ACC, thus providing a promising therapeutic strategy for persistent pain and concurrent anxiety.

Various acupuncture techniques are widely applied in clinics for pain control and dysfunction relief in patients with knee osteoarthritis (KOA). The purpose of this trial was to investigate whether the different acupuncture techniques were more effective in treating joint pain and dysfunction than were sham acupuncture or drug treatment in patients with KOA and to determine the differences in efficacy among them. In this multi-center, single-blind, randomized, controlled trial, participants were randomly assigned to the manual acupuncture (MA), electroacupuncture (EA), warm-needling acupuncture (WA), mild moxibustion (MM), sham acupuncture (SA), or drug treatment (Celebrex) groups. Each participant in the above groups received individual treatments for 4 consecutive weeks. The primary outcome measures included the visual analog scale score (VAS) and the physical function score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Compared with the SA group, the acupuncture technique groups (MA, EA, WA, and MM) had markedly lower patient VAS scores (− 0.61; 95

BackgroundAlthough the relationship between viscera and somato remains unclear, a deeper comprehension of the relationship will maximize the diagnostic and therapeutic benefits. Therefore, this study was conducted to explore the specificity of visceral-somatic associations in the pathological state of chronic stable angina pectoris (CSAP).Methods40 individuals with CSAP participated in the study, while 40 individuals in the healthy control group were age-matched healthy individuals. Four distinct somatic locations dispersed along the heart and lung meridians were subjected to laser doppler flowmetry, infrared thermography, and functional near-infrared spectroscopy in order to assess (1) perfusion unit (PU), (2) temperature, and (3) regional oxygen saturation (rSO2). These three outcomes represented the somatic sites' microcirculatory, thermal, and metabolic properties.ResultsRegarding the microcirculatory characteristics, PU at the somatic sites of the heart meridian (Shenmen(HT7)/Shaohai(HT3)) in the CSAP group substantially increased (P < 0.05) compared to the healthy control group, while there was no statistically significant difference in PU at the somatic sites of the lung meridian between the two groups. Regarding the thermal characteristics, compared with the healthy control group, the temperature of the somatic sites of the heart meridian (Shenmen(HT7)/Shaohai(HT3)), as well as Taiyuan (LU9) of the lung meridian, increased significantly (P < 0.05). With regard to the metabolic features, rSO2 of the somatic site of the heart meridian (Shaohai (HT3)) in the CSAP group decreased significantly (P < 0.05) as compared to the healthy control group. The between-group difference in rSO2 in the lung and heart meridians (Taiyuan (LU9)/Chize (LU5)) and Shenmen (HT7), respectively, was not statistically significant.ConclusionsSpecific somatic sites in the heart meridian typically exhibit more significant changes in their microcirculatory, thermal, and metabolic characteristics than those in the lung meridian, thereby supporting the relative specificity for the visceral-somatic association in the disease state of CSAP. Trial registration: Clinicaltrials.gov (registration number: NCT04046640).

Pain memory, which includes sensory and emotional memory, is one of the main causes of pain complications and prolongation. Recent research has identified the insular cortex (IC) as a critical brain region involved in the integration of information pertaining to pain, emotion, reward, cognition and memory. GABAergic neuronal activity in the IC has been demonstrated to be strongly correlated with the manifestation of pain-related aversive behavior. Electroacupuncture (EA) relieves pain-related aversive memory by activating μ opioid receptors (MORs) in the IC. The results of this study demonstrate that activating MORs in the IC may inhibit GABAergic neuron activity and thus alleviate the relapse of behaviors associated with pain sensory memory and pain-related aversive memory. The relapse of such behaviors was found to be alleviated by EA in model mice; however, antagonism of MORs in the IC reversed the therapeutic effect of EA. In consideration of these findings, we suggest that EA may affect GABAergic neuron activity through activation of MORs in the IC thereby alleviating the relapse of behaviors associated with pain sensory memory and pain-related aversive memory. The study provides novel insights into the mechanisms by which EA chronic pain and behaviors associated with chronic pain-related aversive memory.

BackgroundAdolescent insomnia is a prevalent issue with significant implications for mental and physical well-being. Given the increasing incidence of sleep disorders, there is an urgent need for safe and efficient treatment modalities, particularly non-pharmacological interventions. Auricular point therapy, a prominent element of acupuncture in China, is often employed to address insomnia. However, there remains a lack of research on the efficacy of auricular point-vagus nerve stimulation in managing insomnia among teenagers. To evaluate the efficacy of this interventions and explore the regulatory mechanisms of brain function, a randomized trial is planned.Methods/designThis trial is a single-center, single-blind, randomized controlled study. A total of 174 adolescent patients with insomnia will be randomly assigned to either the treatment or control groups. Over a period of 4 weeks, patients in the experimental group will undergo bilateral auricular point-vagus nerve stimulation, while those in the control group will receive bilateral non-auricular acupoint-vagus nerve stimulation. Data collection will occur at baseline, 1 week into the intervention, 4 weeks post-treatment initiation, and 4 weeks post-treatment completion. The primary outcome measures will include the Pittsburgh Sleep Quality Index (PSQI), Adolescent Sleep Hygiene Habits Scale (ASHS), and Adolescent Sleep Assessment Questionnaire (DSM). Secondary outcome measures encompass the Self-Assessment Scale for Anxiety (SAS), Self-Depression Scale (SDS), Quality of Life Scale (SF-36), and Autonomic Composite Score (COMPASS-31). Other indicators will involve the use of functional magnetic resonance imaging (fMRI), heart rate variability (HRV), and polysomnography (PSG).DiscussionThe findings of this study will provide strong support for the use of auricular-vagus nerve stimulation as a safe and effective non-pharmacological intervention for insomnia. This approach will offer advantages over medication by mitigating the risks of addiction and adverse effects associated with prolonged drug therapy. Furthermore, the results will align with prior research that underscores the positive impact of auricular acupuncture point stimulation on enhancing sleep quality.Clinical trial registrationhttps://www.chictr.org.cn, ChiCTR2400087889.