title: [Effects of intrathecal injection PI3K antagonist on inflammatory cytokines in spinal cord of bone cancer pain model in rats].
abstract: OBJECTIVE
  To investigate the roles of PI3K in bone cancer pain, the present study was performed to demonstrate the changes of pain-related behavior and the production of IL-1β, IL-6 and TNF-α after intrathecal injection of wortmannin (antagonist of PI3K receptors) in rat model.
  
  
  METHODS
  A total of 44 SD rats were randomly divided into 4 groups, sham group (group S), sham + wormannin group (group SW), cancer group (group A), cancer + wortmannin group (group AW). Group S and group W were injected with 10 μl Hank's solution into left tibial medullary cavity; group A and group AW received injections of Walker 256 mammary cancer cells(10 μl, 2×10 cells/ml) into the same place to establish the model of bone cancer pain. In the meantime intratheacal catheterization was performed between L3 and L4 vertrbra on the rats of every group. Nine days after the operation, group S and group A received a single intratheacal injection of saline (0.9%, 10 μl), group SW and group AW received intratheacal wortmannin 0.5 μg/10 μl. Mechanical withdrawal thresholds were measured on the left hind paw before and every 10 min after intrathecal injection. Then the L4-L6 sections of spinal cord 30 min after injection were collected to determine the expression of IL-1β, IL-6 and TNF-α.
  
  
  RESULTS
  At 30 min post-injection, mechanical withdrawal thresholds of groups S, SW, A and AW were (30.1±4.3), (31.7±1.3), (17.2±2.0), (24.8±2.3) g respectively at Day 9 postinoculation (F=22.403, P<0.01), the mechanical withdrawal thresholds in group AW increased obviously versus group A. The expressions of TNF-α in groups S, SW, A and AW were (84.5±6.3), (78.7±12.5), (110.5±7.3), (57.8±4.6) pg/ml. Compared with groups S and W, the expression of TNF-α in group A showed a significant upregulation (F=28.119, P<0.01).
  
  
  CONCLUSIONS
  An intrathecal injection of wortmannin may alleviate hyperalgesia, and inhibit the up-regulated expression of spinal cord inflammatory cytokines TNF-α in rats with bone cancer. PI3K may be involved in the development of bone cancer pain by regulating the expressions of TNF-α.
authors.affiliation: Department of Anesthesiology and Pain Medical center, the First Affiliated Hospital of Jiaxing University, Jiaxing 314000, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Longsheng
authors.initials: L
authors.lastname: Xu
authors.forename: Hanqi
authors.initials: H
authors.lastname: Wang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.forename: Xuyan
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001859:Bone Neoplasms; D001842:Bone and Bones; D016207:Cytokines; D004195:Disease Models, Animal; D006930:Hyperalgesia; D007249:Inflammation; D007278:Injections, Spinal; D012516:Osteosarcoma; D010146:Pain; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors