{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T03:47:48Z","timestamp":1780976868520,"version":"3.54.1"},"reference-count":30,"publisher":"BMJ","issue":"3","funder":[{"name":"Central Colleges Basic Scientific Research Operating Expenses","award":["2632018PY12"],"award-info":[{"award-number":["2632018PY12"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["1600020009"],"award-info":[{"award-number":["1600020009"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation Youth Fund project","award":["81803752"],"award-info":[{"award-number":["81803752"]}]},{"DOI":"10.13039\/501100011360","name":"State Key Laboratory of Natural Medicines","doi-asserted-by":"crossref","award":["SKLNMZZCX201810"],"award-info":[{"award-number":["SKLNMZZCX201810"]}],"id":[{"id":"10.13039\/501100011360","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\"Double First-Class\" University project","award":["CPU2018GY32"],"award-info":[{"award-number":["CPU2018GY32"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2019,12,4]]},"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                  <jats:title>Background and objectives<\/jats:title>\n                  <jats:p>Neuropathic pain is partially refractory to currently available treatments. Although some studies have reported that apoptosis signal-regulating kinase 1 (ASK1) may inhibit chronic pain, the mechanisms underlying this process have not been fully elucidated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Chronic constriction injury (CCI) of the rat sciatic nerve was used to establish a neuropathic pain model. Nociception was assessed using von Frey hair and Hargreaves\u2019 methods. Western blot and immunofluorescence were used to detect the cell signaling pathway. BV2 cell line was cultured for in vitro evaluation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our results indicated that spinal ASK1 was co-expressed with the microglia marker ionized calcium binding adaptor 1. Additionally, intrathecal administration of ASK1 inhibitor suppressed the activation of spinal microglia and attenuated CCI-induced neuropathic pain. The ASK1 inhibitor also decreased the levels of phosphorylated ASK1 (p-ASK1), p65, p38 mitogen-activated protein kinase (MAPK) and tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2) messenger RNA in lipopolysaccharide-stimulated BV2 microglia cells. Intragastric administration of <jats:italic>levo<\/jats:italic>-corydalmine (<jats:italic>l<\/jats:italic>-CDL) significantly attenuated CCI-induced neuropathic pain and inhibited the expression of p-ASK1 in the spinal cord. <jats:italic>l<\/jats:italic>-CDL conspicuously suppressed the activation of spinal microglia in vitro and in vivo. Translocation of nuclearfactor-kappa B (NF-\u03baB) and upregulation of p-p65, TNF-\u03b1, IL-1\u03b2 were inhibited by <jats:italic>l-<\/jats:italic>CDL. Further, the analgesic effects of <jats:italic>l<\/jats:italic>-CDL were associated with reduced levels of phosphorylated protein kinase C (PKC \u03b3), c-JunNH2-terminal kinase, and extracellular signal-regulated kinase.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study showed that the expression of ASK1 in spinal microglia and ASK1 inhibitor suppressed microglia activation via suppression of p38 MAPK\/NF-\u03baB, which ultimately attenuated CCI-induced neuropathic pain. <jats:italic>l-<\/jats:italic>CDL also inhibited the ASK1-P38 MAPK\/NF-\u03baB axis to attenuate CCI-induced neuropathic pain.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rapm-2019-100875","type":"journal-article","created":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T10:14:52Z","timestamp":1577960092000},"page":"219-229","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Levo<i>-<\/i>corydalmine attenuates microglia activation and neuropathic pain by suppressing ASK1-p38 MAPK\/NF-\u03baB signaling pathways in rat spinal cord"],"prefix":"10.1136","volume":"45","author":[{"given":"Wen-Ling","family":"Dai","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ni","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Fa","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Shan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"},{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hua","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,1,2]]},"reference":[{"key":"2025101109323397000_45.3.219.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.01.057"},{"key":"2025101109323397000_45.3.219.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2015.01.018"},{"key":"2025101109323397000_45.3.219.3","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20871"},{"key":"2025101109323397000_45.3.219.4","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.neuron.2018.11.009","article-title":"Microglia in pain: detrimental and protective roles in pathogenesis and resolution of pain","volume":"100","author":"Chen","year":"2018","journal-title":"Neuron"},{"key":"2025101109323397000_45.3.219.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.rapm.2007.01.005"},{"key":"2025101109323397000_45.3.219.6","doi-asserted-by":"crossref","first-page":"9195","DOI":"10.3390\/molecules18089195","article-title":"Inhibition of lipopolysaccharide-induced proinflammatory responses by buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-kB and ERK1\/2 signaling","volume":"18","author":"WJ","year":"2013","journal-title":"Molecules"},{"key":"2025101109323397000_45.3.219.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.06.022"},{"key":"2025101109323397000_45.3.219.8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jbior.2017.10.004","article-title":"Therapeutic application of apoptosis signal-regulating kinase 1 inhibitors","volume":"66","author":"Fujisawa","year":"2017","journal-title":"Adv Biol Regul"},{"key":"2025101109323397000_45.3.219.9","doi-asserted-by":"crossref","unstructured":"Zheng S LY et al . 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