Search Results (113)

Background: Fibromyalgia is a chronic disease that predominantly affects women and lasts over several months, causing problems both for individuals and society. While several studies have demonstrated the potential of electroacupuncture (EA) to alleviate fibromyalgia pain in mice, further research is needed to investigate its underlying mechanisms. Programmed cell death ligand 1 (PD-L1)/PD-1 were first identified to be involved in cancer immunotherapy, and their application to pain management has not been yet investigated. Methods: In this study, we aimed to explore the mechanism underlying the action of PD-L1 on the PD-1 pathway in a mouse model of fibromyalgia. Results: We established such a mouse model using intermittent cold stress (ICS) and confirmed mechanical (D4: 2.02 ± 0.13 g, n = 9) and thermal (D4: 4.28 ± 0.21 s, n = 9) hyperalgesia. We found that EA, intracerebral ventricle (ICV) PD-L1 injection, and transient receptor potential vanilloid 1 (Trpv1) knockout effectively counteracted hyperalgesia. We observed low PD-1 expression in the cerebellum of fibromyalgia mice but increased expression of TRPV1 and pain-related kinases. These phenomena could be further reversed by EA, ICV PD-L1 injection, and Trpv1 knockout. To confirm that these effects were caused by PD-L1 release, we added PD-L1-neutralizing antibodies to the EA and PD-L1 treatment. The analgesic effects and EA and PD-L1 mechanisms were inhibited. Conclusions: Our results elucidate the role of the PD-L1/PD-1 pathway in EA treatment of fibromyalgia and reveal its potential value for fibromyalgia management. Full article

Background: Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with limited treatment efficacy. Alternating current electroacupuncture (AC-EA) represents a novel neuromodulatory approach, though its mechanisms—particularly its influence on the gut–brain axis—remain underexplored. Methods: We investigated the neurobehavioral and microbiological effects of AC-EA in a rat model of PTSD induced by single prolonged stress. Animals received AC-EA at Baihui (GV20) and Mingmen (GV4) acupoints with varying parameters (0.5 mA/20 Hz, 1 mA/20 Hz, and 1 mA/2 Hz). Behavioral tests (open field test, elevated plus maze), histopathological assessments, immunofluorescence for TLR4, and 16S rRNA sequencing of gut microbiota were performed. Results: AC-EA at 1 mA/2 Hz significantly improved exploratory behavior and reduced anxiety-like responses (p < 0.05). This regimen also restored neuronal integrity in the hippocampus and cortex and reversed PTSD-induced gut dysbiosis, enriching beneficial genera such as Ligilactobacillus. Furthermore, AC-EA downregulated hepatic TLR4 expression, indicating suppression of neuroinflammatory signaling. Conclusions: Our findings demonstrate that AC-EA exerts neuromodulatory and microbiota-rebalancing effects via the gut–brain axis, highlighting its potential as a non-invasive therapeutic strategy for PTSD and related brain health disorders. Full article

Chronic pain significantly impairs functional performance in patients with cancer. Although acupuncture is effective for cancer-related pain, its impact on pain-related functional interference remains unclear. This secondary analysis of the PEACE randomized clinical trial included patients with prior cancer diagnoses and musculoskeletal pain for ≥3 months. Participants were randomized to groups undergoing 10 weeks of electro-acupuncture, auricular acupuncture, or a waitlist control. Functional performance was assessed using the Quick-Disability Arm/Shoulder/Hand (Q-DASH) for upper limbs and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscale for lower limbs (higher scores = worse function). Linear mixed models compared changes over time between groups, with week 12 as the primary endpoint. Functional changes were also compared between pain responders and non-responders in the acupuncture arms. Among 360 patients (mean [SD] age, 62.1 [12.7] years; 69.7% women), mean baseline Q-DASH and WOMAC scores were 33.2 (19.8) and 33.3 (20.3). At week 12, both electro-acupuncture and auricular acupuncture significantly improved function versus waitlist: Q-DASH by −7.18 and −9.64 points, respectively, and WOMAC by −6.89 and −7.61 points (all p < 0.001). No differences were found between the two acupuncture groups. Treatment effects on Q-DASH diminished during follow-up, while improvements on WOMAC persisted. Within the acupuncture groups, pain responders achieved greater functional gains than non-responders (Q-DASH, −6.74; WOMAC, −6.16; both p < 0.001). Electro-acupuncture and auricular acupuncture improved upper and lower extremity function in cancer patients with chronic pain. These findings support acupuncture as a potential adjunct in functional rehabilitation for cancer survivors. Full article

Chronic gastritis (CG) is a prevalent digestive disorder. It progresses through multiple stages, has an insidious onset, and can lead to severe complications if untreated. Modern treatments primarily aim to eradicate Helicobacter pylori and relieve symptoms. However, drug resistance and adverse effects often limit their effectiveness. As a primary traditional Chinese medicine (TCM) therapy, acupuncture treats CG through multi-target mechanisms. This review systematically outlines the classification and pathology of CG. It also comprehensively analyzes animal and clinical studies on acupuncture for CG from the past decade. The study summarizes the mechanisms of acupuncture and related therapies for CG, covering gastric mucosal function, metabolism, intestinal flora, gastrointestinal hormones, apoptosis, inflammation, and oxidative stress. It further explores the relationships among diseases, interventions, acupoints, and molecular pathways. Additionally, it compares the therapeutic profiles of different external therapies. The review also examines the current state of clinical research, including the selection of acupoints, treatment duration, and outcome assessment. The results demonstrate that external therapies effectively alleviate common CG symptoms such as abdominal distension, acid reflux, and stomach pain. These treatments also improve gastric mucosal health and modulate serum levels of inflammatory factors, oxidative stress markers, and gastrointestinal hormones. In vivo experiments using chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG) models confirm these benefits, showing changes in key biomarkers and elucidating potential mechanisms. Nevertheless, future high-quality, large-sample clinical trials are still needed to firmly establish efficacy. Further mechanistic studies are also needed to validate the interconnections among relevant signaling pathways. Full article

Background: Alzheimer’s disease (AD) lacks effective therapeutic strategies. Electroacupuncture (EA) offers promising neuroprotective effects, but its underlying mechanisms remain unclear. Objective: To explore the mechanisms of EA’s neuroprotective effects on AD via microbiome and metabolome integration. Methods: Utilizing a well-established model of AD, Senescence-Accelerated Mouse Prone 8 (SAMP8), EA intervention was performed. 16S ribosomal RNA (rRNA) sequencing and serum metabolomics were conducted on SAMP8 mice, SAMP8 mice after EA intervention, and their normal control group Senescence-Accelerated Mouse Resistant 1 (SAMR1) mice. Results: SAMP8 mice were subjected to electroacupuncture (EA) treatment at the Baihui (GV20) and Shenshu (BL23) acupoints for 15 min daily over a period of four weeks. EA enhanced cognitive function and reduced neuronal damage in AD models. The treatment lowered pro-inflammatory cytokines (TNF-α, IL-1β) and AD-related pathologies (tau, Aβ_1-42). EA also rebalanced gut microbiota by increasing beneficial Gastranaerophilales while decreasing harmful Proteobacteria. Additionally, it restored purine and phenylpropanoid metabolism by regulating key metabolites. Importantly, EA reduced levels of specific metabolites linked to pro-inflammatory bacteria (Sphingomonas, Massilia, Escherichia-Shigella), simultaneously decreasing their abundance. These findings highlight EA’s multi-target effects on neuroinflammation, gut microbiota, and metabolic pathways in AD. Notably, the interactions between EA-regulated key metabolites and AD-related targets, predicted via PubChem and ChEMBL databases, remain computational and have not been validated by experimental studies. Conclusions: EA exerts neuroprotective effects in AD via modulation of gut microbiota and metabolic pathways, representing a novel non-pharmacological therapeutic strategy. Full article

This study aimed to evaluate the effects of acupuncture–moxibustion (AM) combined with Locomotor Training (LT) on functional recovery after surgery for Cervical Intervertebral Disc Herniation (IVDH) in dogs. Seventy-nine dogs undergoing ventral slot decompression (VSD) between 2022 and 2025 were enrolled and assigned to either the AM plus LT group (ALRG group) or the LT-only group (LRG group) based on postoperative rehabilitation protocols. To control for bias, post hoc analysis used propensity score matching (PSM) stratified by Rusbridge Grade. Primary outcomes included time to standing and walking recovery, along with Olby scores at five postoperative time points. Secondary endpoints included postoperative analgesic usage rate and duration, as well as long-term prognosis at 6–8 months postoperatively. After PSM, each group comprised 20 dogs. Compared with the LRG group, the ALRG group demonstrated shorter time to standing and walking recovery, better Olby score improvement, and significantly reduced opioid usage duration. Long-term follow-up revealed a higher complete success rate in the ALRG group. All trends were more pronounced in severe cases classified as Rusbridge grades 3 and 4. This study demonstrates the clinical feasibility of combining AM with LT rehabilitation for postoperative recovery in dogs with cervical IVDH. It provided new evidence for optimizing postoperative rehabilitation protocols and supports future large-scale prospective studies. Full article

Background: Insomnia is strongly associated with stimulant use across various populations and for a wide range of substances. It represents a significant clinical problem among individuals with stimulant use disorders, yet treatment guidelines for this specific population are limited. This gap underscores the need for a systematic review to analyze the pharmacological and non-pharmacological treatments for insomnia in individuals with stimulant use disorders. The aim of this review is to determine the efficacy, safety, and limitations of these approaches and their impact on psychiatric symptoms, stimulant use, and adverse events. Methodology: A systematic review was conducted through January–July 2025 using PubMed, Scopus, and Web of Science. The review focused on the management of chronic insomnia associated with stimulant use, including substances such as amphetamines, methylphenidate, nicotine, caffeine, and cocaine. The systematic review was structured in accordance with the PRISMA guidelines, and identified studies were assessed by title/abstract and full-text evaluation. Results: A total of twenty studies were included in the systematic review. Seven studies examined pharmacological interventions, including modafinil, naltrexone/buprenorphine-naloxone, varenicline, combination NRT, and ramelteon. Thirteen studies investigated non-pharmacological approaches, including Cognitive Behavioral Therapy (CBT), Repetitive Transcranial Magnetic Stimulation (rTMS), Electrical Vestibular Nerve Stimulation (VeNS), maximal strength training, electroacupuncture (EA), and probiotics. The majority of interventions demonstrated positive outcomes in reducing insomnia severity, with some participants achieving non-clinical levels. Commonly reported clinical symptoms related to insomnia included difficulty initiating or maintaining sleep, early morning awakening, and sleep dissatisfaction. Conclusions: Both pharmacological and non-pharmacological interventions showed promise. However, the lack of validated guidelines underscores the need for integrated therapeutic approaches that address the complex comorbidity of insomnia, stimulant use, and co-occurring psychiatric conditions. Full article

Background: Shoulder subluxation and pain are common complications of stroke that impair upper limb function. Objectives: This study conducted a systematic review and network meta-analysis to compare multiple therapeutic interventions for post-stroke shoulder subluxation, establishing an evidence-based hierarchy of treatment efficacy to optimize rehabilitation strategies and guide clinical practice. Methods: A comprehensive search was conducted using the MEDLINE, EMBASE, Cochrane, Scopus, and Web of Science databases until 8 August 2025. Randomized controlled trials evaluating treatments for shoulder subluxation, including neuromuscular electrical stimulation (NMES), Kinesio taping, corticosteroid injections, slings, repetitive peripheral magnetic stimulation, and electroacupuncture, were included. The follow-up duration in the included trials ranged from 1 to 12 weeks. Effect sizes were calculated using standardized mean differences with a random-effects model, and treatment rankings were determined using surface under the cumulative ranking curve (SUCRA). Results: Thirteen studies including 402 patients were analyzed. NMES was the most effective intervention for reducing subluxation distance (SUCRA: 84.9), while corticosteroid injections provided the greatest pain relief at rest (SUCRA: 73.6). Kinesio taping was most effective for functional recovery, as measured by the Fugl–Meyer Assessment (SUCRA: 98.5), and for pain relief during activity (SUCRA: 87.7). Conclusions: Our network meta-analysis suggests that different interventions are optimal for specific aspects of post-stroke shoulder impairment. NMES most effectively reduces subluxation distance, whereas corticosteroid injections are most effective for alleviating pain at rest. Kinesio taping appears superior for enhancing functional recovery and reducing pain during movement. These findings, based on short-term follow-up durations (1–12 weeks), provide an evidence-based ranking of interventions to support multimodal rehabilitation and inform clinical decision-making. The observed heterogeneity across studies underscores the need for standardized treatment protocols and rigorous long-term investigations. Full article

Fibromyalgia (FM) is characterized by widespread musculoskeletal pain and tenderness, cognitive dysfunction, fatigue, and insomnia. Electroacupuncture (EA) has documented efficacy against FM-associated pain, while cannabinoid receptor 1 (CB1) plays a critical role in endogenous analgesia. Herein, we examined whether pain relief initiated by EA was linked with differing cerebellar CB1 levels and signaling in an intermittent cold stress (ICS) mouse model of FM. FM-like hyperalgesia and recovery were assessed by measuring mechanical and thermal nociceptive thresholds. Compared to control mice, ICS-induced FM-model mice exhibited a significantly reduced mechanical withdrawal threshold (2.3 ± 0.1 g) and shorter thermal withdrawal latency (4.0 ± 0.5 s), indicative of mechanical and thermal hyperalgesia. Both conditions were reversed by 2 Hz EA but not sham EA. Hyperalgesia was associated with reduced CB1 receptor expression and the enhanced activity of multiple nociceptive signaling pathways (PKA, PI3K, Akt, mTOR, ERK, and NF-kB) in the mouse cerebellum. The 2 Hz EA treatment reliably reversed these abnormalities, while the sham EA treatment did not. Intracerebroventricular injection of the CB1 agonist anandamide (AEA) recapitulated the effects of EA on pain thresholds, while the analgesic effects of EA were blocked by the CB1 antagonist AM251. Precise chemogenetic stimulation at the paraventricular nucleus (PVN) of the hypothalamus reliably induced FM pain. Chemogenetic inhibition at the PVN diminished FM through the CB1 pathway in the cerebellum. Our findings suggest that dysregulation of CB1 expression and aberrant hyperactivity of nociceptive signaling pathways in the cerebellum contribute to the etiology of FM and that the upregulation of CB1 signaling mediates the analgesic efficacy of EA. Full article

Electroacupuncture (EA) has shown analgesic potential for neuropathic pain, yet its underlying molecular mechanisms remain incompletely understood. This study aimed to investigate whether EA relieves neuropathic pain by modulating CCL2/CCR2 signaling and microglial activation in the spinal cord. Neuropathic pain was induced in rats by L5 spinal nerve ligation. EA was administered at acupoints ST36 and GB34 (1 mA, 2 Hz, 30 min) daily from postoperative days 3 to 7. Rats were assigned to anesthetized control (ANE), non-acupoint stimulation (NAP), and acupoint stimulation (ACU) groups. Pain behavior was evaluated using paw withdrawal threshold and latency. Western blot and immunofluorescence were used to assess CCL2, CCR2, Iba1, IL-1β, and TNF-α expression in the L4–L6 spinal cord. EA significantly attenuated mechanical allodynia and thermal hyperalgesia in the ACU group, accompanied by reductions in CCL2, CCR2, microglial marker Iba1, and pro-inflammatory cytokines. Most importantly, intrathecal administration of recombinant CCL2 completely abolished EA’s analgesic effects, establishing the causal necessity of CCL2/CCR2 signaling in EA-mediated analgesia. These findings suggest that EA exerts its analgesic effects through downregulation of the CCL2/CCR2 pathway and inhibition of microglial activation. The reversal of EA’s effects by exogenous CCL2 supports the critical role of spinal chemokine signaling in EA-mediated analgesia. Full article

Background/Objectives: Fibromyalgia causes chronic long-term pain, with symptoms lasting for months to years. Given the lack of evidence-based methods for diagnosing and assessing fibromyalgia, it ranks among the most difficult chronic pain conditions to treat. Programmed cell death ligand 1 (PD-L1) can inhibit acute and chronic pain transmission by inhibiting neuronal ion channels. Methods: Here, we aimed to explore the analgesic efficacy and mechanism of PD-L1/PD1 in an intermittent cold stress-induced fibromyalgia pain mouse model. Results: Von Frey and Hargreaves tests were performed, showing that the mouse model exhibited mechanical (day 4: 2.08 ± 0.13 g, n = 9) and thermal hyperalgesia (day 4: 3.93 ± 0.45 s, n = 9). Electroacupuncture (EA) or intraventricular PD-L1 injection effectively alleviated the nociceptive response and led to low PD-1 levels in the mouse dorsal root ganglia, spinal cord, thalamus, somatosensory cortex, and cerebellum, as measured through Western blots. In contrast, the pain-related kinase levels increased after fibromyalgia induction; these effects were reversed by EA and PD-L1 via the inhibition of microglia/astrocytes and Toll-like receptor 4. Conclusions: Our results show that EA can treat fibromyalgia pain in mice through effects on the PD-L1/PD1 pathway, indicating its potential as a therapeutic target in fibromyalgia. Full article

Background/Objectives: Fibromyalgia is a chronic pain syndrome with unclear etiology, meaning that it is difficult to treat effectively. The stimulation of cannabinoid receptor 1 (CB1) suppresses neuronal excitability and synaptic transmission in nociceptive pathways via reducing activity in the calcium channel and promoting the opening of the potassium channel. Methods: In this study, we examined whether CB1 activity contributes to the antinociceptive efficacy of electroacupuncture (EA) in a mouse fibromyalgia (FM) pain model established using intermittent cold stress (ICS). The model mice demonstrated both mechanical and thermal hyperalgesia measured using the von Frey and Hargreaves tests, respectively. Results: Electroacupuncture effectively reduced both forms of hyperalgesia and enhanced CB1 expression in the dorsal root ganglia, spinal cord, hypothalamus, and periaqueductal gray. In addition, EA attenuated the fibromyalgia-associated reactive transformation of microglia and astrocytes and the activation of the pain-related TLR4–MyD88–TRAF6 signaling pathway. The effects of ICS were also mitigated by the deletion of Trpv1, the gene encoding the transient receptor potential cation channel TRPV1 (capsaicin channel) implicated in nociceptive and inflammatory signaling. Further, the antinociceptive efficacy of EA was partially recapitulated by the acupoint injection of a CB1 agonist and abolished by the injection of a CB1 antagonist, suggesting that activating CB1 is essential for this therapeutic effect. Conclusions: Electroacupuncture can effectively alleviate mechanical and thermal hyperalgesia in a mouse model affected by fibromyalgia pain by activating the CB1 pathway, highlighting the therapeutic potential of CB1 agonism as a therapeutic strategy. Full article

Background: Heat therapy (HT) and electroacupuncture (EA) are widely utilized pain relief methods, but the analgesic mechanisms of their combined application remain unclear. Methods: In acetic acid (AA)-induced writhing test and complete Freund’s adjuvant (CFA)-induced inflammatory pain tests, mice received one of three treatments: EA at bilateral ST36, HT via a 45 °C heating pad, or the combination (EA + HT). To probe underlying pathways, separate groups were pretreated with caffeine, DPCPX (a selective adenosine A₁ receptor antagonist), or naloxone (an opioid receptor antagonist). Spinal expression of glial fibrillary acidic protein (GFAP) and phosphorylated p38 (p-p38) was examined by Western blot and immunofluorescence. Results: Both EA and HT individually reduced AA-induced writhing, with the combination (EA + HT) exhibiting the greatest analgesic effect. EA’s analgesic effect was reversed by caffeine and DPCPX and partially by naloxone, while HT’s effect was reversed by caffeine and DPCPX but was unaffected by naloxone. AA injection elevated spinal p-p38 and GFAP expression, which were attenuated by either EA or HT, with the most substantial suppression observed in the EA + HT group. In the CFA model, both treatments alleviated mechanical allodynia, while the combined treatment resulted in significantly greater analgesia compared to either treatment alone. Conclusions: EA combined with HT synergistically enhances analgesia in both AA and CFA pain models, accompanied by reduced spinal inflammation and astrocyte activation. EA’s analgesic effects appear to involve adenosine A₁ receptor pathways and, to a lesser extent, opioid receptor mechanisms, whereas HT’s effects involve adenosine A₁ receptor pathways. Full article

Background: Percutaneous electrolysis (PE) is a minimally invasive procedure that utilizes galvanic current delivered through a needle. PE is increasingly employed for musculoskeletal disorders, despite the scarcity of scientific evidence supporting its use. The aim of this systematic review is to synthesize the existing evidence and explore the applications of PE in rehabilitation. Methods: In line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search was conducted across the PubMed, Web of Science, Scopus, and PEDro databases from inception to July 2025. The search strategy employed the term “Percutaneous Electrolysis” without applying additional filters or time restrictions, ensuring a comprehensive search. Cited references from screened articles were also evaluated for potential inclusion. Studies were included if they met the following criteria: peer-reviewed articles, intervention-based research, relevance to the topic, and publication in English. Results: Of the 181 papers retrieved, 143 were excluded for various reasons, leaving 38 studies. The evidence suggests that PE appears effective in reducing pain and improving function, particularly when combined with exercises such as eccentric training or stretching, though inconsistencies in protocols and patient characteristics, along with unclear mechanisms, show that it warrants further investigation. Conclusions: In conclusion, while PE emerges as a promising therapeutic strategy for musculoskeletal disorders, its full integration into rehabilitation practice necessitates further rigorous research to standardize treatment protocols, elucidate the underlying mechanism, and validate its cost-effectiveness. These steps are essential to establish PE as a robust and evidence-based option within the field of rehabilitation. Full article

This study investigates the effects of transcutaneous electroacupuncture stimulation (TEAS) on eyeblink rate, EEG, and heart rate variability (HRV), emphasising whether eyeblink data—often dismissed as artefacts—can serve as useful physiological markers. Sixty-six participants underwent four TEAS sessions with different stimulation frequencies (2.5, 10, 80, and 160 pps, with 160 pps as a low-amplitude sham). EEG, ECG, PPG, and respiration data were recorded before, during, and after stimulation. Using non-parametric statistical analyses, including Friedman’s test, Wilcoxon, Conover–Iman, and bootstrapping, the study found significant changes across eyeblink, EEG, and HRV measures. Eyeblink laterality, particularly at 2.5 and 10 pps, showed strong frequency-specific effects. EEG power asymmetry and spectral centroids were associated with HRV indices, and 2.5 pps stimulation produced the strongest parasympathetic HRV response. Blink rate correlated with increased sympathetic and decreased parasympathetic activity. Baseline HRV measures, such as lower heart rate, predicted participant dropout. Eyeblinks were analysed using BLINKER software (v. 1.1.0), and additional complexity and entropy (‘CEPS-BLINKER’) metrics were derived. These measures were more predictive of adverse reactions than EEG-derived indices. Overall, TEAS modulates multiple physiological markers in a frequency-specific manner. Eyeblink characteristics, especially laterality, may offer valuable insights into autonomic function and TEAS efficacy in neuromodulation research. Full article