title: Thalidomide represses inflammatory response and reduces radiculopathic pain by inhibiting IRAK-1 and NF-κB/p38/JNK signaling.
abstract: Intervertebral disc (IVD) disease, the most common cause of disc failure and low back pain, is characterized by age-related changes in the adult disc. In this study we aimed to analyze the potential of thalidomide for the treatment of IVD disease, through identifying and explaining its anti-inflammatory and anti-catabolic activity in both in vitro IVD cell culture and in vivo animal model. Inflammatory response was induced by IL-1β, then the activity and expression of inflammatory mediators and pathways were assessed in the presence or absence of thalidomide. The p38 inhibitor SB203580 was also used to investigate the involvement of the MAPK pathway in the observed effects. Moreover the analgesic properties of thalidomide were analyzed by the von Frey filament test in Sprague-Dawley rats. Our results indicated that thalidomide significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB. Our current study strongly supports the potential of thalidomide for the treatment of pain and inflammation in degenerative disc disease.
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China. Electronic address: tysong1234@163.com.
authors.forename: Tieying
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Kunfeng
authors.initials: K
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050051, Hebei, China.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Pengxu
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, The Sixth Hospital of Shijiazhuang, Shijiazhuang 050054, Hebei, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Ruyv
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Anesthesiology, The First Hospital of Shijiazhuang, Shijiazhuang 050051, Hebei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ya
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011843:Radiculopathy / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D013792:Thalidomide; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Inflammatory response; Interleukin-1β; Intervertebral disc cells; Matrix metalloproteinase; Radiculopathy; Thalidomide