Yahui Wang: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China. ORCID
Chengfei Xu: Department of Anesthesiology, Bengbu Third People's Hospital, Bengbu City, 233000, People's Republic of China.
Peng Liu: Department of Pain Management, the First Affiliated Hospital of Bengbu Medical College, Bengbu City, 233000, People's Republic of China.
Qiuli He: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China.
Shihua Zhang: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China.
Zhihao Liu: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China.
Chaobo Ni: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China.
Liping Chen: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China.
Tong Zhi: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China.
Longsheng Xu: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China. ORCID
Liang Cheng: Department of Anesthesiology, Bengbu Third People's Hospital, Bengbu City, 233000, People's Republic of China.
Xuewu Lin: Department of Pain Management, the First Affiliated Hospital of Bengbu Medical College, Bengbu City, 233000, People's Republic of China.
Ming Yao: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China. ORCID
Huadong Ni: Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People's Republic of China.
Background: Bone cancer pain (BCP) represents one of the most challenging comorbidities associated with cancer metastasis. Long non-coding RNAs (lncRNAs) have garnered attention as potential therapeutic agents in managing neuropathic pain. However, their role in the regulation of nociceptive information processing remains poorly understood. In this study, we observed a significant down-regulation of the spinal lncRNA ENSRNOG00000051325 (lncRNA51325) in a rat model of bone cancer pain. Our study sought to elucidate the potential involvement of lncRNA51325 in the development of BCP by modulating the expression of molecules associated with pain modulation. Methods: We established the BCP model by injecting Walker 256 cells into the tibial plateau of rats. We conducted tests on the pain behaviors and anxiety-like responses of rats through von-Frey test, Gait analysis, and Open Field Test. Spinal lumbar expansion was harvested for molecular biology experiments to explore the relationship between lncRNA51325 and Pumilio RNA binding family member 2 (Pum2). Results: Notably, the overexpression of lncRNA51325 effectively attenuated mechanical allodynia in rats afflicted with BCP, whereas the knockdown of lncRNA51325 induced pain behaviors and anxiety-like responses in naïve rats. Additionally, we observed a time-dependent increase in the expression of Pum2 in BCP-afflicted rats, and intrathecal injection of Pum2-siRNA alleviated hyperalgesia. Furthermore, our investigations revealed that lncRNA51325 exerts a negative modulatory effect on Pum2 expression. The overexpression of lncRNA51325 significantly suppressed Pum2 expression in BCP rats, while the knockdown of lncRNA51325 led to elevated Pum2 protein levels in the spinal cord of naïve rats. Subsequent treatment with Pum2-siRNA mitigated the downregulation of lncRNA51325-induced mechanical allodynia in naïve rats. Conclusion: Our findings indicate that lncRNA51325 plays a role in regulating bone cancer pain by inhibiting Pum2 expression, offering a promising avenue for novel treatments targeting nociceptive hypersensitivity induced by bone metastatic cancer.
