Background: Neuropathic pain is an incurable disease which is defined as a chronic pain caused by a
disease or lesion of the nervous systems. Current treatments can provide a long-lasting pain relief only in a very
limited number of patients with neuropathic pain. MicroRNA can regulate multiple genes and pathways involved
in human diseases. This review focuses on: a) Molecular mechanisms of microRNA biogenesis. b) Targeting,
modifications, and delivery of microRNAs. c) Aberrant expression of microRNAs and their potential therapeutic
targets in neuropathic pain. d) Potential challenges of microRNA therapy in clinical practice, such as off-target effects,
toxicity, delivery hurdles, and target prediction.
Results: This review introduces: 1. Canonical/non-canonical pathway of microRNA biogenesis. 2. Viral/non-viral vectors transporting
microRNAs into target cells. 3. MicroRNA mimics/inhibitors targeting strategies. 4. Aberrantly expressed microRNAs in different animal
neuropathic pain models and their links to underlying mechanisms such as inflammation and ion channel expression. 5. Potential
challenges of microRNAs therapy such as off-target effect, pseudogenes, liver toxicity, delivery hurdles and target prediction.
Conclusion: Although using microRNAs to target neuropathic pain seem promising, their off-target/toxic effects and delivery hurdles
still need to be surmounted.