Introduction: Peripheral nerve injury affects approximately 20 million Americans annually, costing the healthcare system over $150 billion each year. Although current therapies attempt to promote nerve regeneration, only 50% of persons fully regain motor and sensory function, while others retain poor motor control and neuropathic pain. Injured peripheral axons can regenerate, but this is rarely complete due to the slow rate of regeneration. A new therapeutic approach for accelerating peripheral nerve regeneration is needed. One approach is through micro RNA (miRNA) and anti-miRNA therapy, which has already proved fruitful in clinical application for other diseases. Here, we clarify the role of miRNA let-7a and 23b post-injury and assess the efficacy of blocking let7a miRNA in vivo to accelerate the regeneration process.
Methods: Male Sprague-Dawley rats were assigned into three groups: experimental (n=12), sham surgery (n=6) and control (n=6). Sciatic nerve crush (SNC) was performed in the experimental and sham surgery groups, but not in the control group. Data was collected at 7 days post-injury. Animals in the experimental group received a single, 240mg/kg dose of miR-let7a antagomir (an inhibitor of miRNA) via intrathecal injection. We assessed the extent of nerve regeneration and changes in nerve growth factor (NGF) and glutaminase (GLS) expression following SNC and antagomir delivery in the dorsal root ganglia (DRG), the spinal cord (SC) and the sciatic nerve (SN).
Results: miRNA let-7a and 23b correlate with NGF and GLS expression in the SC and DRG. Administration of let-7a antagomirs resulted in upregulation of nerve growth factor (NGF) expression and was associated with improved neural recovery.
Conclusions: Intrathecal administration of Let-7a antagomirs accelerates nerve regeneration and improves functional recovery. We reveal a novel approach to accelerating nerve regeneration and improving the neuropathic pain.
Patient Care: Current study describes a novel approach to accelerating pain regeneration and reducing neuropathic pain. This approach has the potential for translation into the clinical setting.
Learning Objectives: By the conclusion of this session, participants will be able to:
1) Describe the approach to using miRNA inhibitors for accelerating peripheral nerve regeneration
2) Discuss the feasibility of translating these findings into the clinical setting
3) Identify an effective treatment for neuropathic pain, which results from peripheral nerve injury