{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T07:02:45Z","timestamp":1779951765456,"version":"3.53.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study investigates the effects of needle-warming moxibustion (NWM) on cervical spondylotic radiculopathy (CSR) by regulating the activation of the nuclear factor-kappa B (NF-\u03baB) pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A CSR rat model was prepared using the fish wire extrusion method and administered postoperative treatment with NWM or injection with MitoTEMPO, with pain pressure threshold and mechanical pain threshold evaluated. Limb spasm pain-caused gait disorders were assessed using the Kawakami method. Pain mediators [Substance P (SP), Prostaglandin E2 (PGE2), and Neuropeptide Y (NPY)] and inflammatory cytokines, ROS levels, spinal cord tissue damage and positive neurons were assessed by ELISA, DHE, HE, and TUNEL staining, respectively. Serum samples from 100 CSR patients treated with NWM were collected before and after treatment. Serum inflammatory factors were determined by ELISA. Visual Analogue Scale (VAS) scores and Neck Disability Index (NDI) scores were assessed before and after treatment for CSR patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NWM increased pain thresholds and decreased SP, PGE2, and NPY protein expression and gait scores in CSR rats, indicating that NWM alleviated pain and improved motor function in CSR rats. NWM reduced inflammatory factor levels and TUNEL-positive neurons. NWM reduced ROS levels and the NLRP3 pyroptosis pathway and the NF-\u03baB signaling axis-related protein expression in damaged tissue of CSR rats. NWM treatment reduced serum inflammatory factors and VAS and NDI scores in CSR patients. Improvements in NDI scores were positively correlated with reduced levels of IL-1\u03b2, TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      , and IL-6.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NWM attenuates CSR by regulating the activation of the NF-\u03baB pathway, reducing ROS, affecting the activation of the NLRP3 inflammasome, and inhibiting mitochondrial dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1769489","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:18:10Z","timestamp":1779949090000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Needle-warming moxibustion alleviates pain in rats with cervical spondylotic radiculopathy by modulating the NF-\u03baB\/ROS\/NLRP3 pathway"],"prefix":"10.3389","volume":"18","author":[{"given":"Bing","family":"Li","sequence":"first","affiliation":[{"name":"The Fourth Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"The Fourth Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wu","sequence":"additional","affiliation":[{"name":"The Fourth Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Fourth Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Mao","sequence":"additional","affiliation":[{"name":"The Fourth Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1148\/radiol.2016152083","article-title":"Cervical Spondylotic myelopathy: metabolite changes in the primary motor cortex after surgery","volume":"282","author":"Aleksanderek","year":"2017","journal-title":"Radiology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1016\/j.apsb.2021.02.006","article-title":"Gasdermin D in pyroptosis","volume":"11","author":"Burdette","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e2545","DOI":"10.1002\/brb3.2545","article-title":"Direct moxibustion exerts an analgesic effect on cervical spondylotic radiculopathy by increasing autophagy via the act a\/Smads signaling pathway","volume":"12","author":"Cai","year":"2022","journal-title":"Brain Behav."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"799","DOI":"10.13702\/j.1000-0607.191004","article-title":"Effects of mild moxibustion on Beclin-1\/Bcl-2 expression in spinal cord of rats with cervical spondylotic radiculopathy","volume":"45","author":"Cai","year":"2020","journal-title":"Zhen Ci Yan Jiu"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"812362","DOI":"10.3389\/fphar.2022.812362","article-title":"Salidroside ameliorates depression by suppressing Nlrp3-mediated Pyroptosis via P2X7\/Nf-kappaB\/Nlrp3 signaling pathway","volume":"13","author":"Chai","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e029052","DOI":"10.1136\/bmjopen-2019-029052","article-title":"Acupotomy versus acupuncture for cervical spondylotic radiculopathy: protocol of a systematic review and meta-analysis","volume":"9","author":"Chen","year":"2019","journal-title":"BMJ Open"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"284","DOI":"10.3389\/fnmol.2017.00284","article-title":"Methods used to evaluate pain behaviors in rodents","volume":"10","author":"Deuis","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"109505","DOI":"10.1016\/j.intimp.2022.109505","article-title":"Huc-Mscs-derived exosomes attenuate neuropathic pain by inhibiting activation of the Tlr2\/MyD88\/Nf-kappaB signaling pathway in the spinal microglia by targeting Rsad2","volume":"114","author":"Gao","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.3892\/ijmm.2019.4163","article-title":"Role of the thioredoxin interacting protein in diabetic nephropathy and the mechanism of regulating nod-like receptor protein 3 inflammatory corpuscle","volume":"43","author":"Gu","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"102010","DOI":"10.1016\/j.redox.2021.102010","article-title":"Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between Nlrp3 inflammasome and mitophagy","volume":"44","author":"Han","year":"2021","journal-title":"Redox Biol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e36664","DOI":"10.1016\/j.heliyon.2024.e36664","article-title":"Transcriptome and proteomic analysis reveal the protective mechanism of acupuncture on reproductive function in mice with asthenospermia","volume":"10","author":"Hao","year":"2024","journal-title":"Heliyon"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1038\/s41386-024-01863-w","article-title":"Substance P in the medial amygdala regulates aggressive behaviors in male mice","volume":"49","author":"He","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1007\/s11655-024-3821-6","article-title":"Electroacupuncture promotes gastric motility by suppressing Pyroptosis via Nlrp3\/Caspase-1\/Gsdmd signaling pathway in diabetic gastroparesis rats","volume":"31","author":"Huang","year":"2025","journal-title":"Chin. J. Integr. Med."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.nbd.2013.02.013","article-title":"A novel experimental model of cervical spondylotic myelopathy (Csm) to facilitate translational research","volume":"54","author":"Karadimas","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"115099","DOI":"10.1016\/j.fct.2024.115099","article-title":"Apigenin attenuates cisplatin-induced hair cell damage in the zebrafish lateral line","volume":"194","author":"Kong","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1002\/nau.24037","article-title":"Acute spinal cord injury is associated with mitochondrial dysfunction in mouse urothelium","volume":"38","author":"Kullmann","year":"2019","journal-title":"Neurourol. Urodyn."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1111\/ajt.17034","article-title":"Ifi16-sting-Nf-kappaB signaling controls exogenous mitochondrion-induced endothelial activation","volume":"22","author":"Li","year":"2022","journal-title":"Am. J. Transplant."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.bja.2025.04.048","article-title":"Microglia-neuronal communication mediated by P2X4R-Bdnf-TrkB promotes synaptic plasticity and anterior cingulate cortex hyperactivity in muscle pain chronicity","volume":"135","author":"Liang","year":"2025","journal-title":"Br. J. Anaesth."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"4547","DOI":"10.2147\/JIR.S373614","article-title":"Txnip participated in Nlrp3-mediated inflammation in a rat model of cervical Spondylotic myelopathy","volume":"15","author":"Liu","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e26643","DOI":"10.1097\/MD.0000000000026643","article-title":"Investigation on the mechanisms of guiqi huoxue capsule for treating cervical spondylosis based on network pharmacology and molecular docking","volume":"100","author":"Liu","year":"2021","journal-title":"Medicine (Baltimore)"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1151196","DOI":"10.3389\/fphar.2023.1151196","article-title":"The role of Nlrp3 inflammasome-mediated pyroptosis in ischemic stroke and the intervention of traditional Chinese medicine","volume":"14","author":"Long","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref22","first-page":"5059","article-title":"The effect of warm needle moxibustion on lumbar disc herniation","volume":"13","author":"Lu","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1177\/21925682221075290","article-title":"Management of Cervical Spondylotic Radiculopathy: a systematic review","volume":"12","author":"Luyao","year":"2022","journal-title":"Global Spine J"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"6614574","DOI":"10.1155\/2021\/6614574","article-title":"Salidroside suppresses the proliferation and migration of human lung Cancer cells through Ampk-dependent Nlrp3 Inflammasome regulation","volume":"2021","author":"Ma","year":"2021","journal-title":"Oxidative Med. Cell. 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Neuroinflammation"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s11916-016-0552-1","article-title":"The role of acupuncture in pain management","volume":"20","author":"Patil","year":"2016","journal-title":"Curr. Pain Headache Rep."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e3177","DOI":"10.1002\/brb3.3177","article-title":"Electroacupuncture ameliorates pain in cervical spondylotic radiculopathy rat by inhibiting the Camkii\/Creb\/Bdnf signaling pathway and regulating spinal synaptic plasticity","volume":"13","author":"Su","year":"2023","journal-title":"Brain Behav."},{"key":"ref30","first-page":"106","article-title":"Euonymus alatus and its monomers alleviate liver fibrosis both in mice and Lx2 cells by blocking TbetaR1-Smad2\/3 and Tnf-alpha-Nf-kappaB pathways","volume":"11","author":"Wan","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"173266","DOI":"10.1016\/j.ejphar.2020.173266","article-title":"Quercetin attenuates diabetic neuropathic pain by inhibiting mtor\/p70S6K pathway-mediated changes of synaptic morphology and synaptic protein levels in spinal dorsal horn of db\/db mice","volume":"882","author":"Wang","year":"","journal-title":"Eur. J. Pharmacol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e18851","DOI":"10.1097\/MD.0000000000018851","article-title":"Meta-analysis of the therapeutic effect of acupuncture and chiropractic on cervical spondylosis radiculopathy: a systematic review and meta-analysis protocol","volume":"99","author":"Wang","year":"","journal-title":"Medicine (Baltimore)"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1515\/jcim-2024-0132","article-title":"The efficacy of thread embedding acupuncture on pain score, neck disability index, and pressure pain threshold for myofascial pain therapy in the upper trapezius muscle","volume":"22","author":"Winarno","year":"2025","journal-title":"J Complement Integr Med"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"11941","DOI":"10.2147\/IJN.S483091","article-title":"Therapeutic potential of ginger exosome-like nanoparticles for alleviating periodontitis-induced tissue damage","volume":"19","author":"Xie","year":"2024","journal-title":"Int. J. Nanomedicine"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"112817","DOI":"10.1016\/j.intimp.2024.112817","article-title":"Arg2 knockdown promotes G0\/G1 cell cycle arrest and mitochondrial dysfunction in adenomyosis via regulation Nf-kappaB and Wnt\/Beta-catenin signaling cascades","volume":"140","author":"Xu","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.2147\/JPR.S415111","article-title":"Electroacupuncture attenuates neuropathic pain in a rat model of cervical Spondylotic radiculopathy: involvement of spinal cord synaptic plasticity","volume":"16","author":"Yang","year":"2023","journal-title":"J. Pain Res."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e39058","DOI":"10.1016\/j.heliyon.2024.e39058","article-title":"Efficacy and safety of warm needle acupuncture for allergic rhinitis: a systematic review and meta-analysis with trial sequential analysis","volume":"10","author":"Yang","year":"","journal-title":"Heliyon"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1142\/S0192415X24500745","article-title":"Acupuncture and Moxibustion for inflammatory bowel disease: regulatory mechanisms revealed by microbiome and Metabolomic analysis","volume":"52","author":"Yang","year":"","journal-title":"Am. J. Chin. Med."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s40122-022-00357-1","article-title":"Diagnosis and treatment of cervical Spondylotic radiculopathy using selective nerve root block (Snrb): where are we now?","volume":"11","author":"Yang","year":"2022","journal-title":"Pain Ther."},{"key":"ref40","first-page":"463","article-title":"Warming-needle moxibustion for cervical headache: a randomized controlled trial","volume":"36","author":"Yao","year":"2016","journal-title":"Zhongguo Zhen Jiu"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.neulet.2016.09.016","article-title":"Spinal mitochondrial-derived Ros contributes to remifentanil-induced postoperative hyperalgesia via modulating Nmda receptor in rats","volume":"634","author":"Ye","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/mds.21720","article-title":"The role of executive function and attention in gait","volume":"23","author":"Yogev-Seligmann","year":"2008","journal-title":"Mov. Disord."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"3634908","DOI":"10.1155\/2022\/3634908","article-title":"Metformin protects against spinal cord injury and cell Pyroptosis via Ampk\/Nlrp3 Inflammasome pathway","volume":"2022","author":"Yuan","year":"2022","journal-title":"Anal. Cell. Pathol. (Amst.)"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1097\/j.pain.0000000000001489","article-title":"Sirtuin 1 alleviates diabetic neuropathic pain by regulating synaptic plasticity of spinal dorsal horn neurons","volume":"160","author":"Zhang","year":"2019","journal-title":"Pain"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1061220","DOI":"10.3389\/fnmol.2023.1061220","article-title":"Spinal cannabinoid receptor 2 activation alleviates neuropathic pain by regulating microglia and suppressing P2X7 receptor","volume":"16","author":"Zhou","year":"2023","journal-title":"Front. Mol. Neurosci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/jnc.15011","article-title":"Muscone suppresses inflammatory responses and neuronal damage in a rat model of cervical spondylotic myelopathy by regulating Drp1-dependent mitochondrial fission","volume":"155","author":"Zhou","year":"2020","journal-title":"J. Neurochem."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e869","DOI":"10.1002\/iid3.869","article-title":"Comparisons of nonpharmaceutical analgesia and pharmaceutical analgesia on the labor analgesia effect of parturient women","volume":"11","author":"Zhu","year":"2023","journal-title":"Immun Inflamm Dis"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"116901","DOI":"10.1016\/j.jep.2023.116901","article-title":"Shenqisherong pill ameliorates neuronal apoptosis by inhibiting the Jnk\/caspase-3 signaling pathway in a rat model of cervical cord compression","volume":"318","author":"Zhu","year":"","journal-title":"J. Ethnopharmacol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s11011-024-01459-9","article-title":"Bushen Huoxue acupuncture ameliorates Alzheimer's disease by upregulating Marchf3 to induce Nlrp3 ubiquitination and inhibit caspase-1-dependent pyroptosis","volume":"40","author":"Zhu","year":"","journal-title":"Metab. 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