Systemic administration of NIS-lncRNA antisense oligonucleotide alleviates neuropathic pain

Neurosci Lett., 2023 · DOI: 10.1016/j.neulet.2023.137512 · Published: November 20, 2023

Simple Explanation

Neuropathic pain (NP) is a significant health issue with limited effective treatments. The study explores a new strategy using antisense oligonucleotides (ASO) to target nerve injury-specific long noncoding RNA (NIS-lncRNA). The ASO approach has been FDA-approved for neurological diseases, and this research investigates whether systemic administration of NIS-lncRNA ASO can alleviate NP caused by nerve injury. The study found that systemic injection of NIS-lncRNA ASO in mice reduced pain hypersensitivity, suggesting its potential as a clinical treatment for neuropathic pain.

Study Duration

35 days

Participants

Male CD1 mice (7–8 weeks)

Evidence Level

Not specified

Key Findings

1
Systemic administration of NIS-lncRNA ASO significantly alleviated CCI-induced mechanical allodynia, heat hyperalgesia, and cold hyperalgesia in mice.
2
The ASO treatment also mitigated CCI-induced spontaneous pain and reduced hyperactivation of neurons and astrocytes in the spinal cord dorsal horn.
3
NIS-lncRNA ASO blocked the CCI-induced increases in NIS-lncRNA and Ccl2 mRNA levels in the injured dorsal root ganglion (DRG).

Research Summary

This study investigates the effectiveness of systemic administration of NIS-lncRNA ASO in alleviating neuropathic pain (NP) in mice with chronic constriction injury (CCI). The results demonstrate that subcutaneous injection of NIS-lncRNA ASO significantly reduces CCI-induced mechanical allodynia, heat hyperalgesia, and cold hyperalgesia, along with spontaneous pain. The study concludes that systemic administration of NIS-lncRNA ASO produces a stable and long-lasting antinociceptive effect on neuropathic pain, suggesting its potential clinical application.

Practical Implications

Potential Clinical Application

NIS-lncRNA ASO may have utility in neuropathic pain treatment in a clinical setting, offering a new therapeutic avenue.

Less Burdensome Administration

Systemic administration is less burdensome for patients compared to intrathecal administration, potentially improving patient compliance.

Targeted Pain Relief

The ASO strategy provides a targeted approach to pain relief by suppressing the expression of specific genes involved in neuropathic pain.

Study Limitations

1
Potential side effects caused by s.c. injection of NIS-lncRNA ASO should be paid attention to.
2
The polar nature of ASO makes it difficult to cross the blood-brain barrier.
3
Why intrathecal or s.c. ASO takes at least several days to produce analgesic effects remains mysterious

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