{"title":"Meridian systems as spatiotemporal networks: An internal body geographic information system.","authors":"Yeonhee Ryu, Younbyoung Chae","doi":"10.1016/j.joim.2026.08.004","DOIUrl":"https://doi.org/10.1016/j.joim.2026.08.004","url":null,"abstract":"<p><p>We propose a conceptual and methodological approach that treats the human body as an internal geographic information system (GIS) for studying meridian-related phenomena. Instead of searching for a single anatomical substrate, we reinterpret meridians as functional networks embedded in a body-centered coordinate system, where acupoints are modeled as both discrete nodes and probabilistic three-dimensional locations. This body-based spatial platform incorporates two key constructs: reaction fields, which map stimulation-evoked responses across body space and time, and indication fields, which map the spatial distribution of clinical indications. A multilayer body GIS can integrate sensation maps, pain drawings, thermography, electrophysiology, neuroimaging and indication databases. It can then quantify clustering, anisotropy and diffusion-like propagation, and compare meridian-based partitions with dermatomes, nerve fields and indication-based zones. By integrating spatial science and network theory, this perspective shifts meridian research from ontological debates toward empirically testable questions about internal geography. It establishes a spatial foundation for interpreting traditional East Asian medical concepts, and developing shared data structures, quantitative methods and reporting standards for meridian research. Please cite this article as: Ryu Y, Chae Y. Meridian systems as spatiotemporal networks: An internal body geographic information system. J Integr Med. 2026; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei-Ling Huang, Li-Li Wang, Jian-Rong Shi, Qing Liu
{"title":"Acupuncture for Alzheimer's disease: A systematic review and meta-analysis integrating traditional insights and scientific evidence.","authors":"Wei-Ling Huang, Li-Li Wang, Jian-Rong Shi, Qing Liu","doi":"10.1016/j.joim.2026.08.002","DOIUrl":"https://doi.org/10.1016/j.joim.2026.08.002","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD), a leading cause of dementia in the elderly, is characterized by progressive cognitive impairment, and still lacks effective therapeutic interventions.</p><p><strong>Objective: </strong>This systematic review synthesizes the classical theoretical foundations, clinical evidence, and modern mechanistic insights for the use of acupuncture to treat AD.</p><p><strong>Search strategy: </strong>A meta-analysis was conducted based on a comprehensive literature search of PubMed, Embase, the Cochrane Library, CNKI, VIP information, and Wanfang Data, covering the period from inception until September 2025.</p><p><strong>Inclusion criteria: </strong>Eligible randomized controlled trials (RCTs) compared acupuncture (manual or electroacupuncture) with control interventions, including sham acupuncture, donepezil, placebo, or no treatment.</p><p><strong>Data extraction and analysis: </strong>Data were extracted by two reviewers working independently and then analyzed using the meta and meta for packages in R (v4.3.2). Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated.</p><p><strong>Results: </strong>A total of 21 RCTs comprising 1354 participants met the inclusion criteria. Compared with no-treatment controls, acupuncture significantly improved cognitive performance, as measured by the Mini-Mental State Examination (MMSE) (WMD = 3.74, 95% CI: 1.34-6.14), and outperformed placebo controls (WMD = 2.13, 95% CI: 1.39-2.87). Acupuncture showed efficacy comparable to that of donepezil on MMSE and Activity of Daily Living (ADL), suggesting non-inferiority to standard pharmacotherapy. Frequently used acupoints included GV20, ST36, GB20, LR3, and ST40, often combining local (GV24, EX-HN1) and distal (SP10, KI3) points. Reported adverse events were mild and transient, with no significant difference from controls. Biomarker analyses indicated that acupuncture enhanced acetylcholine levels and reduced plasma Aβ<sub>1-40</sub>, Aβ<sub>1-42</sub>, and Tau levels, implying modulation of cholinergic transmission and AD-related pathology.</p><p><strong>Conclusion: </strong>This review highlights acupuncture as a holistic, multi-targeted therapy with promising potential for managing AD. Future research should aim to standardize acupuncture protocols, integrate TCM syndrome differentiation, and adopt neurobiological and imaging techniques to explore mechanisms. Please cite this article as: Huang WL, Wang LL, Shi JR, Liu Q. Acupuncture for Alzheimer's disease: A systematic review and meta-analysis integrating traditional insights and scientific evidence. J Integr Med. 2026; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bridging the gap between syndrome differentiation advocacy and RCT practice: A reflection on the integration of Chinese and Western medicines.","authors":"Si-Yuan Zhu","doi":"10.1016/j.joim.2026.08.001","DOIUrl":"https://doi.org/10.1016/j.joim.2026.08.001","url":null,"abstract":"<p><p>Please cite this article as: Zhu SY. Bridging the gap between syndrome differentiation advocacy and RCT practice: A reflection on the integration of Chinese and Western medicines. J Integr Med. 2026; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quercetin for brain diseases: Preclinical evidence and therapeutic potentials.","authors":"Xiao-Ling Fang, Hui-Ru Chen, Zi-Qiao Xu, Jia-Qi Xu, Xuan-Ying Yin, Hong-Ying Yang, Qi Wang, Shui-Qing Huang","doi":"10.1016/j.joim.2026.07.009","DOIUrl":"https://doi.org/10.1016/j.joim.2026.07.009","url":null,"abstract":"<p><p>This review compiles the preclinical evidence on the therapeutic effects of quercetin in brain diseases, outlines its underlying mechanisms and highlights new insights and future research needs. Quercetin shows robust preclinical efficacy across diverse models of brain diseases, improving neurological function as well as cognitive and behavioral outcomes. The reported benefits include reductions in infarct volume, blood-brain barrier (BBB) disruption, inflammation and oxidative damage, with trends toward structural and functional recovery. These effects stem from pleiotropic, multi-target mechanisms, most consistently involving antioxidant, anti-apoptotic and anti-inflammatory actions, as well as modulation of mitochondrial function and regulation of cell-death/quality-control pathways (e.g., autophagy and ferroptosis). Studies also describe delivery strategies (e.g., nanoparticles, liposomes and exosomes) and combination regimens that enhance brain delivery and overall efficacy. However, its clinical translation is hampered by the BBB permeability and the hormetic dose-response properties of quercetin. Evidence suggests that the dose- and timing-dependent bidirectional effects imply a relatively narrow therapeutic window and potential toxicity or loss of protection at high doses or under specific conditions. Quercetin is a promising neuroprotective candidate or adjunctive strategy that can synergistically target multiple pathological processes associated with brain diseases. These findings provide valuable information for the discovery of new drugs from traditional medicines and natural products. However, translation is constrained due to its poor aqueous solubility, limited bioavailability, suboptimal BBB penetration and rapid metabolism, as well as the need to define safety limits related to dose-, schedule- and metabolite-dependent bidirectional effects. Future work should optimize the delivery system and appropriate combinations, clarify exposure-response relationships, elucidate key active metabolites and long-term safety profiles, define appropriate patient populations and confirm clinically significant benefits through rigorous clinical studies. Please cite this article as: Fang XL, Chen HR, Xu ZQ, Xu JQ, Yin XY, Yang HY, Wang Q, Huang SQ. Quercetin for brain diseases: Preclinical evidence and therapeutic potentials. J Integr Med. 2026; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hangzhou declaration on the global development of artificial intelligence in traditional Chinese medicine.","authors":"Xiao-Hui Fan, Yu Li, Xiao-Bo Lai, Jun-Hua Zhang, Hai-Yan Li, Kong-Fa Hu, Jie Li, Jian-Xin Chen, Hu-Dan Pan, Chuan-Biao Wen, Qing Ye, Hong-Xing Kan, Xin-Xue Li, Pan-Fei Li, Yu Hu, Kai-Xian Chen, Bo-Li Zhang","doi":"10.1016/j.joim.2026.07.010","DOIUrl":"https://doi.org/10.1016/j.joim.2026.07.010","url":null,"abstract":"<p><p>Artificial intelligence (AI) is having a profound impact on the production of medical knowledge, research paradigms, healthcare services and the health industry. Traditional Chinese medicine (TCM), a valuable part of human heritage and an important global health resource, is entering a period of historic innovation through its integration with AI. This convergence offers significant opportunities for the collation of classical literature, the inheritance of clinical experience, diagnosis and treatment, drug discovery, talent cultivation, industrial upgrading and health management. However, AI-enabled TCM is still in its infancy and faces challenges relating to theoretical compatibility, data quality, scientific evaluation, algorithmic transparency, ethical governance, standardization, interdisciplinary training and international coordination. The Hangzhou Declaration on the Global Development of Artificial Intelligence in Traditional Chinese Medicine sets out a shared position and a consensus based on principles for trustworthy innovation in this emerging field. It emphasizes preserving the essence of TCM while pursuing innovation, prioritizing clinical value and patient safety, strengthening ethical governance, improving data standards and scientific evaluation, fostering interdisciplinary collaboration, advancing international standards, bridging the digital divide, and cultivating globally competent talent. The Declaration aims to guide the responsible, open, inclusive and sustainable development of AI-enabled TCM, contributing to the health and well-being of humanity. Please cite this article as: Fan XH, Li Y, Lai XB, Zhang JH, Li HY, Hu KF, Li J, Chen JX, Pan HD, Wen CB, Ye Q, Kan HX, Li XX, Li PF, Hu Y, Chen KX, Zhang BL. Hangzhou declaration on the global development of artificial intelligence in traditional Chinese medicine. J Integr Med. 2026; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A commentary on the cautious use of moxibustion at Chize (LU5) and Weizhong (BL40) from the perspective of classical theory: Interpreting the divergent thermal effects in a modern randomized controlled trial.","authors":"Dong'e Huang, Jun-Qing Dong","doi":"10.1016/j.joim.2026.07.008","DOIUrl":"https://doi.org/10.1016/j.joim.2026.07.008","url":null,"abstract":"","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Letter to the editor regarding \"Photothermal effect of invasive laser acupuncture: A computational study with experimental validation\".","authors":"Hao-Li Zhang, Hong-Liang Fu, Ai-de Chen","doi":"10.1016/j.joim.2026.07.007","DOIUrl":"https://doi.org/10.1016/j.joim.2026.07.007","url":null,"abstract":"","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diana Rodríguez-Vera, Marvin A Soriano-Ursúa, Rodolfo Pinto-Almazán, Ivonne Maciel Arciniega-Martínez, Aldo Arturo Reséndiz-Albor, Arely Vergara-Castañeda, Carmen Valadez-Vega, Ángel Morales-González, Eduardo Osiris Madrigal-Santillán, Jazmín García-Machorro, Gabriela Ibañez-Cervantes, José A Morales-González
{"title":"Berberine as a modulator in autism: Insights into mechanisms of action and therapeutic potential.","authors":"Diana Rodríguez-Vera, Marvin A Soriano-Ursúa, Rodolfo Pinto-Almazán, Ivonne Maciel Arciniega-Martínez, Aldo Arturo Reséndiz-Albor, Arely Vergara-Castañeda, Carmen Valadez-Vega, Ángel Morales-González, Eduardo Osiris Madrigal-Santillán, Jazmín García-Machorro, Gabriela Ibañez-Cervantes, José A Morales-González","doi":"10.1016/j.joim.2026.07.006","DOIUrl":"https://doi.org/10.1016/j.joim.2026.07.006","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a broad neurodevelopmental disorder characterized by impairments in social communication and limited, repetitive patterns of behavior and interests. It is frequently associated with comorbidities, including gastrointestinal dysfunction, and immune and oxidative disturbances. Recent discoveries have revealed that nutritional therapies designed to target certain pathophysiological processes may serve as adjunctive treatments. Berberine is a natural isoquinoline alkaloid isolated from various medicinal herbs. It possesses anti-inflammatory and antioxidant activities and has demonstrated neuroprotective effects in preclinical models. Recent preclinical studies have shown that berberine may help modulate key pathways implicated in ASD, such as gut microbiota-brain axis, neuroinflammatory cascades, mitochondrial dysfunction and oxidative stress responses. Berberine can restore intestinal barrier integrity, suppress microglial activation, balance neurotransmitter systems, and regulate key signaling pathways including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2), which is considered a plausible basis for investigating it as an adjunctive strategy for ASD-associated biological pathways. Moreover, the impact of berberine on the composition of gut microbiota may be associated with behavioral modulation and immune homeostasis. This review explores the mechanistic basis of berberine activity in ASD. Existing preclinical evidence and indirect clinical data suggest that berberine can be regarded as an adjunct intervention and a biological therapeutic approach targeting ASD-related biological pathways. However, current evidence remains preliminary and needs to be further validated in subsequent clinical studies. Please cite this article as: Rodríguez-Vera D, Soriano-Ursúa MA, Pinto-Almazán R, Arciniega-Martínez IM, Reséndiz-Albor AA, Vergara-Castañeda A, Valadez-Vega C, Morales-González Á, Madrigal-Santillán EO, García-Machorro J, Ibañez-Cervantes G, Morales-González JA. Berberine as a modulator in autism: Insights into mechanisms of action and therapeutic potential. J Integr Med. 2026; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Zhao, Lin-Xin You, Jing-Yu Zhang, Wei Wang, Si-Jia Li, Ji-Quan Li
{"title":"Electroacupuncture at LI11 and SP10 attenuates inflammation and pruritus in a rat model of passive cutaneous anaphylaxis-like urticaria via mast cell modulation related to transient receptor potential vanilloid 1.","authors":"Yan Zhao, Lin-Xin You, Jing-Yu Zhang, Wei Wang, Si-Jia Li, Ji-Quan Li","doi":"10.1016/j.joim.2026.07.004","DOIUrl":"https://doi.org/10.1016/j.joim.2026.07.004","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the effects of electroacupuncture (EA) on mast cell activation and transient receptor potential vanilloid 1 (TRPV1)-related signaling in skin tissue using a rat model of passive cutaneous anaphylaxis (PCA)-like urticaria.</p><p><strong>Methods: </strong>An immunoglobulin E (IgE)/high-affinity Fc receptor for IgE (FcεRI)-mediated PCA-like urticaria model was established in rats by anti-ovalbumin serum injection followed by ovalbumin challenge. Rats were randomly divided into negative control, model, EA, Cap (capsaicin + model), and Cap + EA groups. Capsaicin was administered subcutaneously in the Cap and Cap + EA groups to activate cutaneous TRPV1. After model establishment, rats in the EA and Cap + EA groups underwent EA stimulation at LI11 (Quchi) and SP10 (Xuehai) for seven consecutive days. Urticarial responses were assessed using Evans blue dye extravasation, wheal area, and scratching bouts. Histopathological changes were assessed using hematoxylin-eosin staining, and mast cell numbers were quantified by toluidine blue staining. Mast cell-derived mediators in sensitized skin and serum cytokine levels were quantified using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry, immunofluorescence, and Western blot analyses were performed to assess TRPV1-related protein expression.</p><p><strong>Results: </strong>EA significantly alleviated inflammatory responses and pruritic behavior in rats in the ovalbumin-induced PCA-like urticaria model. Histopathological examination revealed marked attenuation of skin lesions and reduced mast cell-associated pathological changes following EA. ELISA demonstrated decreased levels of mast cell-derived mediators in sensitized skin, accompanied by reduced serum inflammatory cytokine levels. Immunohistochemistry, immunofluorescence, and Western blot analyses further showed that EA suppressed TRPV1-related protein expression and mast cell-mediated inflammatory responses.</p><p><strong>Conclusion: </strong>EA at LI11 and SP10 alleviates local inflammation and pruritus in a PCA-like urticaria model, with effects associated with mast cell regulation and modulation of TRPV1-related signaling. Please cite this article as: Zhao Y, You LX, Zhang JY, Wang W, Li SJ, Li JQ. Electroacupuncture at LI11 and SP10 attenuates inflammation and pruritus in a rat model of passive cutaneous anaphylaxis-like urticaria via mast cell modulation related to transient receptor potential vanilloid 1. J Integr Med. 2026; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Low-frequency electroacupuncture alleviates neuropathic pain via cannabinoid receptor type 2 signaling in the spinal cord dorsal horn.","authors":"Zhou-Yuan Wei, Jing-Jing Zhang, Can Lin, Si-Yi Li, Yu-Rong Kang, Jing-Qi Liang, Zhou-Qi Liu, Xiao-Fen He, Xiao-Mei Shao, Jian-Qiao Fang, Yong-Liang Jiang","doi":"10.1016/j.joim.2026.07.005","DOIUrl":"https://doi.org/10.1016/j.joim.2026.07.005","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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, Z","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148608880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}