title: Protocadherin20 promotes excitatory synaptogenesis in dorsal horn and contributes to bone cancer pain.
abstract: The majority of patients with metastatic bone disease experience moderate to severe pain. Bone cancer pain is usually progressive as the disease advances, and is very difficult to treat due to the poor understanding of the underlying mechanisms. Recent studies demonstrated that synaptic plasticity induces spinal cord sensitization and contributes to bone cancer pain. However, whether the synaptic plasticity is due to modifications of existing synapses or the formation of new synaptic connections is still unknown. Here we showed that a carcinoma implantation into a rats' tibia induced a significant increase in the number of excitability synapses in the dorsal horn, which contributes to the development of bone cancer pain. Previous studies identified that non-clustered protocadherins play significant roles in neuronal development and other implications in neurological disorders. In the present study, we showed that Protocadherin20 was significantly increased in the dorsal horn of cancer-bearing rats, while knockdown of Protocadherin20 with RNAi lentivirus reversed bone cancer-induced pain behaviors and decreased excitatory synaptogenesis in ipsilateral dorsal horn. In an in vitro study, we showed that knockdown of Protocadherin20 inhibited neurite outgrowth and excitatory synapse formation of dorsal neurons. These findings indicate that Protocadherin20 is required for the development of bone cancer pain probably by promoting the excitability synaptogenesis.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province 442000, China.
authors.forename: Changbin
authors.initials: C
authors.lastname: Ke
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Caijuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province 442000, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Huilian
authors.initials: H
authors.lastname: Bu
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Cai
authors.affiliation: Integrative Molecular and Biomedical Sciences Graduate Program CNRC Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Antentor Othrell
authors.initials: AO
authors.lastname: Hinton
authors.affiliation: Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yktian@tjh.tjmu.edu.cn.
authors.forename: Yuke
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000150:complications*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010146:Pain / Q000209:etiology* / Q000473:pathology*; D010147:Pain Measurement; D020671:Posterior Horn Cells / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000473:pathology*; D013569:Synapses / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D015820:Cadherins; D009419:Nerve Tissue Proteins
keywords: BCP; Bone cancer; PCDH; Pain; Protocadherin20; RNA interference; RNAi; Spinal cord; Synapse; bone cancer pain; protocadherin