骨癌疼痛（BCP）是癌症患者中最普遍和难治的症状之一，迫切需要解决。大量研究揭示了Cav3.2 T型钙通道在慢性疼痛中的关键作用，然而，它在BCP中的参与以及具体的分子机制尚未完全阐明。通过Western blot检测组织和细胞中的Cav3.2、胰岛素样生长因子1（IGF-1）、IGF-1受体（IGF-1R）和低氧诱导因子1α（HIF-1α）的表达水平。使用X射线和微CT检测大鼠骨破坏情况。采用免疫荧光法检测蛋白质的表达和空间定位在脊髓后角。电泳迁移实验用于验证HIF-1α与Cav3.2之间的相互作用。结果显示，Cav3.2通道的表达上调，阻断该通道可减轻BCP大鼠的机械触痛和热痛。此外，IGF-1/IGF-1R信号抑制不仅可以逆转BCP诱导的Cav3.2和HIF-1α的上调，还可以减轻BCP大鼠的痛觉敏感性。IGF-1的抑制增加了Cav3.2的表达水平，而HIF-1α siRNA预处理可消除这种效应。此外，核HIF-1α结合到Cav3.2的启动子上，调控Cav3.2的转录水平，HIF-1α的敲低抑制了IGF-1诱导的Cav3.2和痛觉行为的上调。这些发现表明，脊髓Cav3.2 T型钙通道通过调节IGF-1/IGF-1R/HIF-1α信号通路，在大鼠骨癌疼痛的发展过程中起着核心作用。© 2023作者。

Bone cancer pain (BCP) is one of the most ubiquitous and refractory symptoms of cancer patients that needs to be urgently addressed. Substantial studies have revealed the pivotal role of Cav3.2 T-type calcium channels in chronic pain, however, its involvement in BCP and the specific molecular mechanism have not been fully elucidated.The expression levels of Cav3.2, insulin-like growth factor 1(IGF-1), IGF-1 receptor (IGF-1R) and hypoxia-inducible factor-1α (HIF-1α) were detected by Western blot in tissues and cells. X-ray and Micro CT used to detect bone destruction in rats. Immunofluorescence was used to detect protein expression and spatial location in the spinal dorsal horn. Electrophoretic mobility shift assay used to verify the interaction between HIF-1α and Cav3.2.The results showed that the expression of Cav3.2 channel was upregulated and blockade of this channel alleviated mechanical allodynia and thermal hyperalgesia in BCP rats. Additionally, inhibition of IGF-1/IGF-1R signaling not only reversed the BCP-induced upregulation of Cav3.2 and HIF-1α, but also decreased nociceptive hypersensitivity in BCP rats. Inhibition of IGF-1 increased Cav3.2 expression levels, which were abolished by pretreatment with HIF-1α siRNA in PC12 cells. Furthermore, nuclear HIF-1α bound to the promoter of Cav3.2 to regulate the Cav3.2 transcription level, and knockdown of HIF-1α suppresses the IGF-1-induced upregulation of Cav3.2 and pain behaviors in rats with BCP.These findings suggest that spinal Cav3.2 T-type calcium channels play a central role during the development of bone cancer pain in rats via regulation of the IGF-1/IGF-1R/HIF-1α pathway.© 2023 The Author(s).