Neurogenic pain rises because of nervous system damage or dysfunction and is the most difficult to treat among other pathological pains. Acupuncture has been reported as a great treatment option for neurogenic pain owing to its unlimited advantages. However, previous studies on the analgesic effects of acupuncture for NP were scattered and did not form a whole. In this study, we first comprehensively review the relevant basic articles on acupuncture for NP published in the last 5 years and summarize the analgesic mechanisms of acupuncture in terms of nerve signaling, neuro-immune crosstalk, and metabolic and oxidative stress regulation. Acupuncture inhibits the upstream excitatory system and suppresses neuronal transmission efficiency by downregulating glutamate, NMDA receptors, P2XR, SP, CGRP, and other neurotransmitters and receptors in the spinal cord, as well as plasma channels such as TRPV1, HCN. It can also activate the downstream pain inhibitory pathway by upregulating opioid peptide (β-endorphin), MOR receptors, GABA and GABA receptors, bi-directional regulating 5-hydroxytryptamine (5-HT) and its receptors (upregulate 5-HT 1A and downregulate 5-HT7R) and stimulating hypothalamic appetite-modifying neurons. Moreover, neuroinflammation in pain can be inhibited by acupuncture through inhibiting JAK2/STAT3, PI3K/mTOR pathways, down regulating chemokine receptor CX3CR1 on microglia and up regulating adenosine receptor A1Rs on astrocytes, inhibiting the activation of glia and reducing TNF-α and other inflammatory substances. Acupuncture also inhibits neuronal glucose metabolism by downregulating mPFC's GLUT-3 and promotes metabolic alterations of the brain, thus exerting an analgesic effect. In conclusion, the regulation of nerve signal transduction and neuroimmune crosstalk at the peripheral and central levels mediates the analgesic effects of acupuncture for neuropathic pain in an integrated manner. These findings provide a reliable basis for better clinical application of acupuncture in the management of neuropathic pain.

To know the research progress of cupping therapy all over the world, the authors analyze the research of cupping therapy in recent 5 years. It indicates that cupping therapy can be applied to extensive curable disease, but has poor clinical evidence. Some improvements in the mechanism research of cupping therapy have been made, but it needs further research. The adverse events of cupping therapy attract attention. The standardization of cupping therapy has emerged.

Cerebral edema, erupting simultaneously with severe ischemic stroke, might lead to increased intracranial pressure, cerebral herniation, and ultimately death. Studies conducted previously by our team have demonstrated the fact that bloodletting puncture at hand twelve Jing-well points (HTWP) could alleviate cerebral edema, which mainly results from the disruption of blood-brain barrier (BBB). The study, therefore, was first designed to demonstrate whether BBB-protection serves an important role in the edema-relief effect of HTWP bloodletting, based on which to research the molecular mechanism underlying. The rats were made into model suffering from permanent middle cerebral artery occlusion (pMCAO) and then bloodletting puncture were treated at HTWP once a day. Wet and dry weight method was adopted to evaluate the degree of brain edema, evans blue extravasation and electron microscopy were used to evaluate the integrity of the BBB, and RT-qPCR was carried out to analyze the expression level of occludin, claudin-5, ICAM-1, and VEGF. Results revealed that bloodletting puncture treatment could reduce water content of brain and the permeability of BBB caused by ischemic stroke. In bloodletting puncture group, ameliorated tight junctions could be observed under electron microscopy. It was demonstrated in further study that, in bloodletting group, compared with pMCAO one, the expression levels of occludin and claudin-5 were up-regulated, while ICAM-1 and VEGF were down-regulated. In conclusion, bloodletting puncture at HTWP might play a significant role in protecting the tight junctions of BBB, thus alleviating cerebral edema induced by ischemic stroke. Therefore, the therapy of bloodletting puncture at HTWP may be a promising strategy for acute ischemic stroke in the future.

Cognitive impairment is a prevalent neurological disorder that burdens families and the healthcare system. Current conventional therapies for cognitive impairment, such as cholinesterase inhibitors and N-methyl-d-aspartate receptor antagonists, are unable to completely stop or reverse the progression of the disease. Also, these medicines may cause serious problems with the digestive system, cardiovascular system, and sleep. Clinically, stimulation of acupoints has the potential to ameliorate the common symptoms of a variety of cognitive disorders, such as memory deficit, language dysfunction, executive dysfunction, reduced ability to live independently, etc. There are common acupoint stimulation mechanisms for treating various types of cognitive impairment, but few systematic analyses of the underlying mechanisms in this domain have been performed. This study comprehensively reviewed the basic research from the last 20 years and found that acupoint stimulation can effectively improve the spatial learning and memory of animals. The common mechanism may be that acupoint stimulation protects hippocampal neurons by preventing apoptosis and scavenging toxic proteins. Additionally, acupoint stimulation has antioxidant and anti-inflammatory effects, promoting neural regeneration, regulating synaptic plasticity, and normalizing neural circuits by restoring brain functional activity and connectivity. Acupoint stimulation also inhibits the production of amyloid β-peptide and the phosphorylation of Tau protein, suggesting that it may protect neurons by promoting correct protein folding and regulating the degradation of toxic proteins via the autophagy-lysosomal pathway. However, the benefits of acupoint stimulation still need to be further explored in more high-quality studies in the future.

Knee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by progressive articular cartilage degeneration, synovial inflammation, and abnormal subchondral bone remodeling, with no curative treatment currently available. Mesenchymal stem cells (MSCs) and their extracellular vesicles (MSC-EVs) have emerged as promising therapeutic strategies for KOA due to their anti-inflammatory, regenerative, and immunomodulatory properties. Clinical studies demonstrate that intra-articular MSCs injection significantly alleviates pain, improves joint function, and exhibits a favorable safety profile. MSC-EVs show enhanced therapeutic potential owing to their low immunogenicity, high stability, and targeted delivery capabilities. This review systematically examines the therapeutic role of MSCs and MSC-EVs in KOA treatment. Mechanistic studies reveal that MSC-EVs ameliorate joint inflammatory microenvironments by regulating macrophage polarization, inhibiting key inflammatory pathways (NF-κB, MAPK), and suppressing pro-inflammatory cytokine release (IL-1β, TNF-α). Furthermore, MSC-EVs protect extracellular matrix integrity and promote cartilage regeneration by upregulating chondrogenic markers (Sox9, aggrecan, type II collagen) while downregulating matrix-degrading enzymes (MMP-13, ADAMTS5). Additionally, MSC-EVs enhance chondrocyte proliferation and migration while inhibiting apoptosis and senescence, potentially through activation of YAP and JAK/STAT signaling pathways. These multifaceted mechanisms collectively facilitate cartilage repair and regeneration. Advances in engineered EVs technology and novel delivery systems provide strategies to further enhance MSC-EVs efficacy. Engineered EVs modified with chondrocyte-targeting peptides or loaded with therapeutic molecules (drugs, miRNAs, siRNAs) can deliver bioactive compounds to specific sites and precisely regulate chondrocyte function, thereby alleviating KOA symptoms. This review comprehensively examines the clinical efficacy and underlying mechanisms of MSCs and MSC-EVs in KOA treatment, discusses current clinical application challenges, and outlines future research directions for advancing precision therapeutic strategies.