title: Involvement of EphB1 receptor/ephrinB1 ligand in bone cancer pain.
abstract: In prior studies, Eph/ephrin system was demonstrated to be involved in inflammatory and neuropathic pain modulation. The present study was to investigate whether the spinal Eph/ephrin signaling was involved in modulation of spinal inflammatory cytokines in bone cancer pain (BCP) of rats. BCP was induced by intra-tibial inoculation of Walker 256 mammary gland carcinoma cells. The expressions of EphB1/ephrinB1 in spinal cord (SC) and dorsal root ganglia (DRG) were determined. At 16 days post inoculation, the pain relieving effect and the mRNA levels of inflammatory cytokines were detected after intrathecal administration of EphB1-Fc (blocker of EphB1 receptor, 10μg). The results showed that the EphB1/ephrinB1 expression was significantly increased in SC, but ephrinB1 was decreased in DRG after Walker 256 inoculation. The mechanical allodynia induced by bone cancer was significantly alleviated by intrathecal administration of EphB1-Fc. Furthermore, the RT-PCR analysis showed that the mRNA levels of IL-1β, IL-6 and TNF-α were significantly increased at 16 days post Walker 256 inoculation and were significantly suppressed by intrathecal administration of EphB1-Fc in SC. We concluded that Eph/ephrin might be involved in the maintenance of mechanical allodynia, via modulating the expression of spinal inflammatory cytokines, in the present rat model of BCP. This study suggested that Eph/ephrin signaling would be a potential target for the treatment of BCP.
authors.affiliation: Department of Anesthesiology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Qi-Liang
authors.initials: QL
authors.lastname: Mao-Ying
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Chen
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Yang
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Wang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Tan
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D002279:Carcinoma 256, Walker / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D007150:Immunohistochemistry; D007278:Injections, Spinal; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D010146:Pain / Q000209:etiology* / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D036225:Receptor, EphB1 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D036225:Receptor, EphB1