microRNAs in nociceptive circuits as predictors of future clinical applications

Abstract

Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs – and microRNAs (miRNAs) in particular – regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesized as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioral components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals.

Practical Considerations of Convection Enhanced Delivery for Novel Therapies Treating Spinal Cord Injury Related Neuropathic Pain

“…Different disease processes, such as peripheral nerve injury, inflammatory diseases, cancer, and spinal cord injury show an alteration in miRNA expression suggesting that novel treatments could developed to respond to this alteration. Specific miRNAs may develop as new molecular targets for pain prevention and relief [64]. Sequencing of miRNA utilized to identify miRNAs in primary sensory neurons related to neuropathic pain [65].…”

Role of MicroRNA in Visceral Pain

“…Several studies identified a deregulation of miR-29a/b in pain conditions such as in spinal dorsal horn-induced muscle inflammation, complex regional pain syndrome (CRPS), and chronic constriction injury. 84,85 However, the target proteins of miR-29a/b and their subsequent regulatory mechanisms in pain processing are not clearly defined.…”

Circulating microRNA Signatures in Rodent Models of Pain

“…miRNAs are known to play an important role in many diseases [7] and their stability in bodily fluids make them highly suitable as potential biomarkers [8]. Recent reviews have catalogued the studies linking miRNAs to various pain conditions, and miRNAs likely play a role in the development of chronic pain owing to their alteration of gene expression [9][10][11][12][13][14].…”

“…Studies that attempt to pursue similar molecular biomarkers between animals and humans may provide valuable information to align preclinical studies with human outcomes. Several studies have examined miRNA expression in the dorsal root ganglion (DRG), trigeminal ganglion, and spinal cord resulting from inflammatory pain models such as complete Freund's adjuvant (CFA), capsaicin, and carrageenan, as well as neuropathic pain models such as spinal nerve ligation (SNL), spared nerve injury (SNI), chronic constriction injury, and sciatic nerve crush [9][10][11][12][13][14]. However, changes in miRNA expression in whole blood from these models have not previously been reported.…”