Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314001, P.R. China.
Department of Anesthesiology, Zhuzhou Central Hospital, Zhuzhou, Hunan 412000, P.R. China.
Mol Med Rep. 2019 Nov;20(5):4695-4705. doi: 10.3892/mmr.2019.10702. Epub 2019 Sep 24.
Treatment of cancer‑induced bone pain (CIBP) is challenging in clinical settings. Oxycodone (OXY) is used to treat CIBP; however, a lack of understanding of the mechanisms underlying CIBP limits the application of OXY. In the present study, all rats were randomly divided into three groups: The sham group, the CIBP group, and the OXY group. Then, a rat model of CIBP was established by inoculation of Walker 256 tumor cells from rat tibia. Phosphoproteomic profiling of the OXY‑treated spinal dorsal cords of rats with CIBP was performed, and 1,679 phosphorylated proteins were identified, of which 160 proteins were significantly different between the CIBP and sham groups, and 113 proteins were significantly different between the CIBP and OXY groups. Gene Ontology analysis revealed that these proteins mainly clustered as synaptic‑associated cellular components; among these, disks large homolog 3 expression was markedly increased in rats with CIBP and was reversed by OXY treatment. Subsequent domain analysis of the differential proteins revealed several significant synaptic‑associated domains. In conclusion, synaptic‑associated cellular components may be critical in OXY‑induced analgesia in rats with CIBP.
治疗癌症相关性骨痛（CIBP）在临床环境中具有挑战性。羟考酮（OXY）用于治疗 CIBP；然而，对 CIBP 潜在机制的理解不足限制了 OXY 的应用。在本研究中，所有大鼠被随机分为三组：假手术组、CIBP 组和 OXY 组。然后，通过接种来自大鼠胫骨的 Walker 256 肿瘤细胞建立 CIBP 大鼠模型。对 CIBP 大鼠 OXY 处理的脊髓背根中的磷酸化蛋白质组进行分析，鉴定出 1,679 个磷酸化蛋白，其中 160 个蛋白在 CIBP 和假手术组之间存在显著差异，113 个蛋白在 CIBP 和 OXY 组之间存在显著差异。GO 分析显示这些蛋白主要聚类为突触相关细胞成分；其中，CIBP 大鼠中 disks large homolog 3 的表达明显增加，OXY 治疗可逆转这种情况。随后对差异蛋白进行结构域分析，揭示了几个显著的突触相关结构域。总之，突触相关细胞成分可能是 OXY 诱导 CIBP 大鼠镇痛的关键。
