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Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
LncRNA 51325 Alleviates Bone Cancer Induced Hyperalgesia Through Inhibition of Pum2
Yahui Wang1,2, Chengfei Xu3, Peng Liu2
1Department 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.
Insights
Bone cancer pain (BCP) is challenging. Spinal lncRNA51325 inhibits Pum2, reducing pain and anxiety, offering new therapeutic targets for BCP.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Bone cancer pain (BCP) is a significant challenge in cancer metastasis.
- Long non-coding RNAs (lncRNAs) show potential for neuropathic pain management.
- The role of lncRNAs in nociception processing is not well understood.
Purpose of the Study:
- To investigate the role of spinal lncRNA ENSRNOG00000051325 (lncRNA51325) in bone cancer pain.
- To explore the relationship between lncRNA51325 and Pumilio RNA binding family member 2 (Pum2).
- To elucidate the therapeutic potential of lncRNA51325 in BCP.
Main Methods:
- Established a rat model of BCP by injecting Walker 256 cells into the tibial plateau.
- Assessed pain behaviors and anxiety-like responses using von-Frey, gait analysis, and open field tests.
- Analyzed the expression of lncRNA51325 and Pum2 in spinal cord tissue.
Main Results:
- Overexpression of lncRNA51325 attenuated mechanical allodynia in BCP rats.
- Knockdown of lncRNA51325 induced pain and anxiety in naïve rats.
- lncRNA51325 negatively modulated Pum2 expression, suppressing its levels in BCP rats.
Conclusions:
- lncRNA51325 plays a crucial role in regulating bone cancer pain by inhibiting Pum2.
- Targeting lncRNA51325 offers a promising therapeutic strategy for nociceptive hypersensitivity in BCP.
- This study provides insights into the molecular mechanisms underlying BCP.
Related Concept Videos
lncRNA - Long Non-coding RNAs
Abnormal Proliferation
Nociception
Analgesia and Pain Management

