title: Inhibitory effects of intrathecal p38β antisense oligonucleotide on bone cancer pain in rats.
abstract: OBJECTIVE
  To evaluate the effects of intrathecal administration p38β antisense oligonucleotide on the development of bone cancer pain rats.
  
  
  METHODS
  Forty female SD rats weighing 180~220 g were randomly divided into 4 groups (n = 10 each): Group A (control group): intra-tibial injection of 3 μl Hank's solution; group B (model group): intra-tibial injection of 3 μl MADB-106 mammary gland carcinoma cells of rats (4.8 × 10(3)/μl); group C (p38β-SODN 20 μg); group D (p38β-ASODN 20 μg). The model procedures in group C and D were same to those in the group B. From the 14th day after operation, p38β-SODN 20 μg and p38β-ASODN 20 μg were respectively intrathecally administrated in group C and D once daily for 6 days whereas normal saline was for group A and B. Mechanical withdrawal threshold and radiant heat threshold of rat hind paws were measured before operation and every other day until 22 d of post-operation. The lumbar 4-6 spinal cord was removed on the 22(nd) day. The expression of spinal p38β protein was determined by Western blot.
  
  
  RESULTS
  No significant differences in mechanical withdrawal threshold and radiant heat threshold were found at all time points in control group. During the first 6 days after operation there were obvious differences in radiant heat stimulus between control group between the other groups (P < 0.05); During 14-22 days after operation, mechanical pain threshold and radiant heat threshold between p38β-SODN group and Model group were significantly changed compared with that in control group (P < 0.05). However, the differences were not remarkable between control group and p38β-ASODN group (P > 0.05). The expression of p38β protein in lumbar spinal cord was significantly higher between p38β-SODN group and Model group than that in control group (P < 0.05). There was no significant difference in p38β protein expression between p38β-ASODN group and control group (P > 0.05).
  
  
  CONCLUSIONS
  Hyperalgesia induced by bone cancer can be inhibited by intrathecal administration of p38β antisense oligonucleotide, which is achieved by reducing expression of p38β protein.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital, Jianghan University Wuhan 430072, P. R. China ; Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430030, P. R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430030, P. R. China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Xiang
authors.affiliation: Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430030, P. R. China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Ye
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan 430030, P. R. China.
authors.forename: Xue-Bi
authors.initials: XB
authors.lastname: Tian
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007278:Injections, Spinal; D048290:Mitogen-Activated Protein Kinase 11 / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D048290:Mitogen-Activated Protein Kinase 11
keywords: Bone cancer pain; antisense oligonucleotides; hyperalgesia; p38beta; spinal dorsal horn