title: Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.
abstract: OBJECTIVE
  To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats.
  
  
  METHODS
  A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro.
  
  
  RESULTS
  BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus.
  
  
  CONCLUSIONS
  Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Zhen-Peng
authors.initials: ZP
authors.lastname: Song
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Bing-Rui
authors.initials: BR
authors.lastname: Xiong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xue-Hai
authors.initials: XH
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.affiliation: School of Psychology, Social Work and Human Sciences, University of West London, Brentford, Middlesex, TW8 9GA, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Manyande
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ya-Qun
authors.initials: YQ
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yu-Ke
authors.initials: YK
authors.lastname: Tian
mesh_terms: D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D001859:Bone Neoplasms / Q000150:complications* / Q000276:immunology / Q000473:pathology; D000072716:Cancer Pain / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008911:Minocycline / Q000627:therapeutic use*; D016328:NF-kappa B / Q000276:immunology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000700:Analgesics; D000900:Anti-Bacterial Agents; D016328:NF-kappa B; D008911:Minocycline