Therapeutic Implication of miRNAs as an Active Regulatory Player in the Management of Pain: A Review

Abstract

Chronic pain is frequently associated with neuropathy, inflammation, or the malfunctioning of nerves. Chronic pain is associated with a significant burden of morbidity due to opioid use, associated with addiction and tolerance, and disability. MicroRNAs (miRs) are emerging therapeutic targets to treat chronic pain through the regulation of genes associated with inflammation, neuronal excitability, survival, or de-differentiation. In this review, we discuss the possible involvement of miRs in pain-related molecular pathways. miRs are known to regulate high-conviction pain genes, supporting their potential as therapeutic targets.

Keywords: miRNAs; pain; pain management; receptor.

Figure 1

Role of miRs in altered gene expression and pain receptors [49]. Diagram showing the targets of miRs that are dysregulated in neuropathic pain and how they are implicated in intracellular signaling. The miRs (miR144, miR206, miR93, miR98, miR544, and miR206) are downregulated during neuropathic pain, according to red downward arrows; in contrast, upward green arrows indicate the elevation of miRs (miR15, miR16, miR155, miR221, and miR7a) during neuropathic pain.

Figure 2

miR-199, TRPV1, visceral hypersensitivity, and visceral pain may have a mechanistic link. Several potentially special benefits over traditional retroviral gene delivery methods are provided by lentiviruses, which deliver miRs in vivo. The primary functions of these are to infect non-dividing cells, including dorsal root ganglion neuron cells, and to produce stable, long-lasting gene/miRNA expression. This work delivered and overexpressed miR-199a to suppress the expression of TRPV1 using lentiviruses. Pictures depict the associated molecular pathways. Lower left panel: Stressors in the environment cause damage to the stomach, which starts a chain reaction that makes the body hypersensitive to certain stimulants. A reduction in miR-199 and an increase in TRPV1 expression could be indicative of this hypersensitive condition [99].

Figure 3

Polymorphism effect of miRs. The figure shows the formation of miRs and their polymorphism effects, like translation repression and DNA degradation, by targeting mRNA.