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.
Keywords: BCP; Bone cancer; PCDH; Pain; Protocadherin20; RNA interference; RNAi; Spinal cord; Synapse; bone cancer pain; protocadherin.
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