{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:04:51Z","timestamp":1790535891396,"version":"4.1.0"},"reference-count":237,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"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":["81870873"],"award-info":[{"award-number":["81870873"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801111"],"award-info":[{"award-number":["81801111"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022A1515012198"],"award-info":[{"award-number":["2022A1515012198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Guangdong Province of China","award":["81870873"],"award-info":[{"award-number":["81870873"]}]},{"name":"Natural Science Foundation of Guangdong Province of China","award":["81801111"],"award-info":[{"award-number":["81801111"]}]},{"name":"Natural Science Foundation of Guangdong Province of China","award":["2022A1515012198"],"award-info":[{"award-number":["2022A1515012198"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The neuroimmune mechanism underlying neuropathic pain has been extensively studied. Tumor necrosis factor-alpha (TNF-\u03b1), a key pro-inflammatory cytokine that drives cytokine storm and stimulates a cascade of other cytokines in pain-related pathways, induces and modulates neuropathic pain by facilitating peripheral (primary afferents) and central (spinal cord) sensitization. Functionally, TNF-\u03b1 controls the balance between cell survival and death by inducing an inflammatory response and two programmed cell death mechanisms (apoptosis and necroptosis). Necroptosis, a novel form of programmed cell death, is receiving increasing attraction and may trigger neuroinflammation to promote neuropathic pain. Chronic pain is often accompanied by adverse pain-associated emotional reactions and cognitive disorders. Overproduction of TNF-\u03b1 in supraspinal structures such as the anterior cingulate cortex (ACC) and hippocampus plays an important role in pain-associated emotional disorders and memory deficits and also participates in the modulation of pain transduction. At present, studies reporting on the role of the TNF-\u03b1\u2013necroptosis pathway in pain-related disorders are lacking. This review indicates the important research prospects of this pathway in pain modulation based on its role in anxiety, depression and memory deficits associated with other neurodegenerative diseases. In addition, we have summarized studies related to the underlying mechanisms of neuropathic pain mediated by TNF-\u03b1 and discussed the role of the TNF-\u03b1\u2013necroptosis pathway in detail, which may represent an avenue for future therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms23137191","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T23:59:22Z","timestamp":1656460762000},"page":"7191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Neuroimmune Mechanisms Underlying Neuropathic Pain: The Potential Role of TNF-\u03b1-Necroptosis Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Yi-Wen","family":"Duan","sequence":"first","affiliation":[{"name":"Pain Research Center and Department of Physiology, Zhongshan Medical School, Sun Yat-sen University, 74 Zhongshan Road. 2, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Xia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao-Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Pain Research Center and Department of Physiology, Zhongshan Medical School, Sun Yat-sen University, 74 Zhongshan Road. 2, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zang","sequence":"additional","affiliation":[{"name":"Pain Research Center and Department of Physiology, Zhongshan Medical School, Sun Yat-sen University, 74 Zhongshan Road. 2, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1089\/jir.2019.0085","article-title":"Constitutive Inflammatory Cytokine Storm: A Major Threat to Human Health","volume":"40","author":"Gupta","year":"2020","journal-title":"J. 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