microRNA let-7i-5p mediates the relationship between muscle fat infiltration and neck pain disability following motor vehicle collision: a preliminary study

Abstract

Persistent neck-pain disability (PNPD) is common following traumatic stress exposures such as motor vehicle collision (MVC). Substantial literature indicates that fat infiltration into neck muscle (MFI) is associated with post-MVC PNPD. However, little is known about the molecular mediators underlying this association. In the current study, we assessed whether microRNA expression signatures predict PNPD and whether microRNA mediate the relationship between neck MFI and PNPD. A nested cohort of 43 individuals from a longitudinal study of MVC survivors, who provided blood (PAXgene RNA) and underwent magnetic resonance imaging (MRI), were included in the current study. Peritraumatic microRNA expression levels were quantified via small RNA sequencing, neck MFI via MRI, and PNPD via the Neck Disability Index two-weeks, three-months, and twelve-months following MVC. Repeated measures regression models were used to assess the relationship between microRNA and PNPD and to perform mediation analyses. Seventeen microRNA predicted PNPD following MVC. One microRNA, let-7i-5p, mediated the relationship between neck MFI and PNPD. Peritraumatic blood-based microRNA expression levels predict PNPD following MVC and let-7i-5p might contribute to the underlying effects of neck MFI on persistent disability. In conclusion, additional studies are needed to validate this finding.

Expression and Biological Functions of miRNAs in Chronic Pain: A Review on Human Studies

“…Biologic pathways targeted by pain-associated miRNAs include extracellular matrix receptor interaction, TGF-β signaling, amphetamine addiction and axon guidance, all contributing to stress, pain pathogenesis and persistent posttraumatic disability related to neck pain. Furthermore, let-7i-5p expression, previously associated with adipose tissue function, appeared to mediate the association between neck muscles fat infiltration and neck-pain related disability [ 62 ].…”

Morphology and composition of the ventral neck muscles in individuals with chronic whiplash related disorders compared to matched healthy controls: a cross-sectional case–control study

“…When the fat signal was removed from the MRI imaging in the study by Elliott et al [ 25 ] the results regarding muscle size of SCM was inconsistent between healthy and controls. Differences in findings among the studies may be caused by different aims, study populations, scanning techniques, different segmental levels measured, different measurements of CSA, MFI and combining muscles [ 9 , 39 ].…”

“…Despite the lack of understanding the precise mechanisms underlying these changes, findings from the basic sciences point to specific molecular processes. For example, the micro ribonucleic acid (RNA) let-7i-5p, which participants in the recruitment and function of brite adipocytes [ 38 ], was shown to mediate the relationship between MFI and neck disability after a whiplash injury, giving a new piece in the complicated puzzle [ 39 ]. There remains inconclusive evidence if the muscles changes are local to the site of injury (e.g., cervical spine) or extend to the distal muscles, suggesting a more systemic consequence [ 40 ].…”

Fat Infiltration of Multifidus Muscle Is Correlated with Neck Disability in Patients with Non-Specific Chronic Neck Pain

“…A clear limitation of our study was the neglect to measure all flexor and extensor muscles (both deep and superficial) as well as serum inflammatory biomarker levels (notably TNF-α) [ 55 ] or microRNA let-7i-5p [ 59 ] in exploring the relationship between muscle function measures and morphological change. Future studies might also examine the relationship between muscle morphological change and other factors such as psychological states.…”