{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:24:39Z","timestamp":1791858279770,"version":"4.3.4"},"reference-count":195,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82405597, 82174526, 82274676, 82374613"],"award-info":[{"award-number":["82405597, 82174526, 82274676, 82374613"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Neuroinflammation is a key immunological driver of spinal sensitization and the transition from acute to chronic pain. Although mechanical interventions can reduce pain, the immuno-inflammatory mechanisms linking mechanical cues to resolution of spinal neuroinflammation remain poorly integrated and inconsistently defined. A major gap is the lack of a mechanobiological framework that connects mechanotransduction with glial activation, cytokine\/chemokine signaling, and neuroimmune synaptic plasticity, and translates these mechanisms into measurable biomarkers and reproducible protocols. Here, we synthesize preclinical and clinical evidence showing how mechanical stimuli may modulate neuroinflammation-driven sensitization. We summarize mechanotransduction pathways that shape microglial and astrocytic reactivity, inflammatory signaling, and downstream remodeling of ion channels, receptors, and synaptic circuits. We also discuss how mechanical interventions may shift the spinal inflammatory microenvironment by improving perfusion and metabolic homeostasis. Finally, we outline candidate biomarker panels and highlight key limitations, including heterogeneity in dosing, outcomes, and translational models. Overall, mechanical forces may act as immunomodulatory cues that reprogram neuroinflammation and weaken spinal sensitization, supporting a mechanistic basis for non-pharmacological analgesia. Future progress requires standardized mechanical dosing, mechanism-informed biomarkers, and rigorous translational pipelines to enable quantifiable, personalized mechanotherapy for chronic pain.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1791900","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:21:31Z","timestamp":1777522891000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Mechanical cues as immunomodulators in neuroinflammation-driven spinal sensitization: analgesic mechanisms and therapeutic strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Li-ya","family":"Tang","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-shang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-xia","family":"Kuang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of University of South China","place":["Hengyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-shan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese 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