Systemic administration of NIS-lncRNA antisense oligonucleotide alleviates neuropathic pain

被引:1
|
作者
Berkman, Tolga [1 ]
Li, Xiang [1 ]
Liang, Yingping [1 ]
Korban, Anna [1 ]
Bekker, Alex [1 ]
Tao, Yuan-Xiang [1 ,2 ,3 ,4 ]
机构
[1] State Univ New Jersey, New Jersey Med Sch Rutgers, Dept Anesthesiol, Newark, NJ 07103 USA
[2] State Univ New Jersey, Rutgers New Jersey Med Sch, Dept Pharmacol Physiol & Neurosci, Newark, NJ USA
[3] State Univ New Jersey, Dept Cell Biol & Mol Med, Rutgers New Jersey Med Sch, Newark, NJ 07103 USA
[4] Rutgers State Univ, Dept Anesthesiol, New Jersey Med Sch, 185 S Orange Ave,MSB,F-661, Newark, NJ 07103 USA
关键词
Antisense oligonucleotides; Nerve injury-specific long noncoding RNA; Systemic administration; Dorsal root ganglion; Nerve trauma; Neuropathic pain; DORSAL-ROOT GANGLION; SPINAL-CORD; NERVE TRAUMA; CONTRIBUTES; RECEPTOR;
D O I
10.1016/j.neulet.2023.137512
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Objective: The antisense oligonucleotide (ASO) is an FDA-approved strategy in the treatment of neurological diseases. We have shown the viability of using intrathecal ASO to suppress nerve injury-specific long noncoding RNA (NIS-lncRNA) in dorsal root ganglion (DRG), resulting in a stable and long-lasting antinociceptive effect on NP. This study examined whether systemic administration of NIS-lncRNA ASO relieved the chronic constriction injury (CCI)-induced nociceptive hypersensitivity. Methods: A single subcutaneous injection of NIS-lncRNA ASO at a dose of 1,000 mu g was carried out 7 days after CCI or sham surgery in male mice. Behavioral tests were performed one day before surgery and at different days after surgery. DRG and spinal cord were finally collected for quantitative real-time RT-PCR and Western blot assays. Results: NIS-lncRNA ASO significantly alleviated CCI-induced mechanical allodynia, heat hyperalgesia, and cold hyperalgesia starting on day 14 or 21 post-ASO injection and lasting for at least 7 days on the ipsilateral side. Additionally, CCI-induced spontaneous pain and ipsilateral dorsal horn neuronal and astrocyte hyperactivation were blocked on day 28 after NIS-lncRNA ASO injection. As predicted, the CCI-induced increases in the levels of NIS-lncRNA and its downstream target C-C motif chemokine ligand 2 in the ipsilateral lumbar 3 and 4 DRGs were attenuated on day 28 following NIS-lncRNA ASO injection. Conclusion: Our findings indicate that systemic administration of NIS-lncRNA ASO also produces a stable and long-lasting antinociceptive effect on neuropathic pain. NIS-lncRNA ASO may have potential clinical application in the treatment of this disorder.
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页数:6
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