Effect of intrathecal NIS-lncRNA antisense oligonucleotides on neuropathic pain caused by nerve trauma, chemotherapy, or diabetes mellitus

British Journal of Anaesthesia, 2023 · DOI: 10.1016/j.bja.2022.09.027 · Published: November 24, 2022

Simple Explanation

This study investigates a new approach to treating neuropathic pain using antisense oligonucleotides (ASOs) to target a specific non-coding RNA called NIS-lncRNA. The rationale is that blocking the increased expression of NIS-lncRNA in injured dorsal root ganglia (DRG) can mitigate neuropathic pain. The researchers tested the effects of intrathecal injections of NIS-lncRNA ASOs in mice with neuropathic pain caused by nerve trauma, chemotherapy, or diabetes. They examined the expression of DRG NIS-lncRNA and CCL2 (an NIS-lncRNA downstream target) and assessed nociceptive hypersensitivity. The study found that intrathecal NIS-lncRNA ASOs attenuated pain responses in all three models of neuropathic pain without causing cellular toxicity, suggesting a potential clinical application for neuropathic pain management.

Study Duration

Not specified

Participants

Adult male CD1 mice (about 7e8 weeks)

Evidence Level

Not specified

Key Findings

1
Intrathecal NIS-lncRNA antisense oligonucleotides attenuated CCI-induced mechanical allodynia, heat hyperalgesia, cold hyperalgesia, and ongoing nociceptive responses, without changing basal or acute nociceptive responses and locomotor function.
2
Intrathecal NIS-lncRNA antisense oligonucleotides blocked CCI-induced increases in NIS-lncRNA and CCL2 in the ipsilateral L3 and L4 DRG and hyperactivities of neurones and astrocytes in the ipsilateral L3 and L4 spinal cord dorsal horn.
3
Similar results were found in antisense oligonucleotides-treated mice after spinal nerve ligation or intraperitoneal injection of paclitaxel or streptozotocin.

Research Summary

This study examined the effect of intrathecal injection of NIS-lncRNA antisense oligonucleotides on neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve, spinal nerve ligation, or chemotherapy/diabetes induction. The results showed that intrathecal NIS-lncRNA antisense oligonucleotides attenuated CCI-induced mechanical allodynia, heat hyperalgesia, cold hyperalgesia, and ongoing nociceptive responses, without changing basal or acute nociceptive responses and locomotor function. These ﬁndings further validate the role of NIS-lncRNA in trauma-, chemotherapy-, or diabetes-induced neuropathic pain and demonstrate potential clinical application of NIS-lncRNA antisense oligonucleotides for neuropathic pain management.

Practical Implications

Potential Clinical Application

NIS-lncRNA antisense oligonucleotides might have utility in the treatment of neuropathic pain in a clinical setting, given that antisense oligonucleotides are an FDA-approved approach.

Novel Therapeutic Target

NIS-lncRNA represents a novel therapeutic target for neuropathic pain, particularly given its role in multiple etiologies including trauma, chemotherapy, and diabetes.

Mechanism of Action

The antinociceptive effect of NIS-lncRNA ASOs is likely attributable to the consequent absence of increased CCL2 expression, the reductions in DRG neuronal hyperexcitability and primary afferent neurotransmitter release, and ultimately mediating decrease in dorsal horn central sensitisation.

Study Limitations

1
Potential unwanted effects on renal or hepatic function, coagulation, and complement or antibody activation need to be considered.
2
Further studies are needed to determine whether systemic administration of NIS-lncRNA antisense oligonucleotides can lead to anti-nociceptive effects on neuropathic pain.
3
The reason why ASOs did not signiﬁcantly affect basal DRG NIS-lncRNA expression is unknown.

Your Feedback

Was this summary helpful?

Back to Pharmacology