Fu Jie, Zhao Baoxia, Ni Chaobo, Ni Huadong, Xu Longsheng, He Qiuli, Xu Miao, Xu Chengfei, Luo Ge, Zhu Jianjun, Tao Jiachun, Yao Ming
The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University/The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
PPAR Res. 2021 Aug 25;2021:6086265. doi: 10.1155/2021/6086265. eCollection 2021.
Bone cancer pain (BCP) is a serious clinical problem that affects the quality of life of cancer patients. However, the current treatment methods for this condition are still unsatisfactory. This study investigated whether intrathecal injection of rosiglitazone modulates the noxious behaviors associated with BCP, and the possible mechanisms related to this effect were explored. We found that rosiglitazone treatment relieved bone cancer-induced mechanical hyperalgesia in a dose-dependent manner, promoted the expression of peroxisome proliferator-activated receptor- (PPAR-) in spinal cord neurons, and inhibited the activation of the nuclear factor-kappa B (NF-B)/nod-like receptor protein 3 (NLRP3) inflammatory axis induced by BCP. However, concurrent administration of the PPAR- antagonist GW9662 reversed these effects. The results show that rosiglitazone inhibits the NF-B/NLRP3 inflammation axis by activating PPAR- in spinal neurons, thereby alleviating BCP. Therefore, the PPAR-/NF-B/NLRP3 signaling pathway may be a potential target for the treatment of BCP in the future.
骨癌疼痛（BCP）是一个严重的临床问题，会影响癌症患者的生活质量。然而，目前针对这种情况的治疗方法仍不尽人意。本研究调查了鞘内注射罗格列酮是否能调节与BCP相关的伤害性反应，并探讨了与此效应相关的可能机制。我们发现，罗格列酮治疗以剂量依赖的方式减轻了骨癌诱导的机械性痛觉过敏，促进了脊髓神经元中过氧化物酶体增殖物激活受体-（PPAR-）的表达，并抑制了BCP诱导的核因子-κB（NF-κB）/NOD样受体蛋白3（NLRP3）炎症轴的激活。然而，同时给予PPAR-拮抗剂GW9662可逆转这些效应。结果表明，罗格列酮通过激活脊髓神经元中的PPAR-来抑制NF-κB/NLRP3炎症轴，从而减轻BCP。因此，PPAR-/NF-κB/NLRP3信号通路可能是未来治疗BCP的潜在靶点。
