Correlation of miRNA expression with intensity of neuropathic pain in man

Abstract

Background Peripheral nerve injury causes changes in expression of multiple receptors and mediators that participate in pain processing. We investigated the expression of microRNAs (miRNAs) – a class of post-transcriptional regulators involved in many physiological and pathophysiological processes – and their potential role in the development or maintenance of chronic neuropathic pain following lingual nerve injury in human and rat. Methods We profiled miRNA expression in Sprague-Dawley rat and human lingual nerve neuromas using TaqMan® low-density array cards. Expression of miRNAs of interest was validated via specific probes and correlated with nerve injury-related behavioural change in rat (time spent drinking) and clinical pain (visual analogue scale (VAS) score). Target prediction was performed using publicly available algorithms; gene enrichment and pathway analysis were conducted with MetaCore. Networks of miRNAs and putative target genes were created with Cytoscape; interaction of miRNAs and target genomes in rat and human was displayed graphically using CircosPlot. Results rno-miR-138 was upregulated in lingual nerve of injured rats versus sham controls. rno-miR-138 and rno-miR-667 expression correlated with behavioural change at day 3 post-injury (with negative (rno-miR-138) and positive (rno-miR-667) correlations between expression and time spent drinking). In human, hsa-miR-29a was downregulated in lingual nerve neuromas of patients with higher pain VAS scores (painful group) versus patients with lower pain VAS scores (non-painful). A statistically significant negative correlation was observed between expression of both hsa-miR-29a and hsa-miR-500a, and pain VAS score. Conclusions Our results show that following lingual nerve injury, there are highly significant correlations between abundance of specific miRNAs, altered behaviour and pain scores. This study provides the first demonstration of correlations between human miRNA levels and VAS scores for neuropathic pain and suggests a potential contribution of specific miRNAs to the development of chronic pain following lingual nerve injury. Putative targets for candidate miRNAs include genes related to interleukin and chemokine receptors and potassium channels.

MicroRNA profiling of the pig periaqueductal grey (PAG) region reveals candidates potentially related to sex-dependent differences

“…Two more miRNAs identified in complex regional pain syndrome (let-7c, miR-185) [92] and fibromyalgia suffering patients (miR-103a-3p, miR-30b-5p) [93] were also DE in this study. Furthermore, Leinders and colleagues reported miR-146a-5p to be altered in peripheral neuropathies [97], while Tavares-Ferreira's team identified altered expression of miR-138 in lingual nerve neuromas [100]. When it comes to profiled migraine miRNAs, the differential expression of miR-27b [94] and miR-34c, -124-3p, -375, and -532-5p [95] was also shown in our study in females vs. males.…”

“…Furthermore, numerous studies allowed characterization of miRNAome signatures of patients suffering from different types of pain and identification of miRNAs with potential to serve as pain subtype and intensity biomarkers [92][93][94][95][96][97][98][99][100]. A handful of those miRNAs was also identified in this study as differentially expressed in the PAG region between females and males (Supplementary file 2).…”

Identifying the Biomarkers of Spinal Cord Injury and the effects of Neurotrophin-3 Based on MicroRNA and mRNA Signature

“…MiR-3072 has been found to be related to the decrease of damage and paralysis of lower limbs following spinal cord injury (SCI) [21]. rno-miR-667 may be associated with presence of nerve injury-induced hypersensitivity [22]. Therefore, we speculated that OPRL1 targeted by rno-miR-3072 and rno-miR-667-5p could play an important role in neurological injury and the neurotrophin-3 treatment.…”

A Review of the Clinical and Therapeutic Implications of Neuropathic Pain

“…The role of exosomes, or extracellular microvesicles involved in intercellular communication, is not negligible in this context. These types of structures are involved in pathologies that determine both inflammatory and NP, namely osteoarthritis, rheumatoid arthritis, inflammatory bowel diseases, neurodegenerative pathologies, complex regional pain syndrome, and peripheral nerve injury [ 96 , 97 , 98 , 99 , 100 , 101 ]. Regarding NP, exosomes are released and taken up by neurons based on synaptic activity, enabling inter-neuronal communication [ 102 ].…”