Introduction

Lumbar Spinal Stenosis (LSS) and Chronic Low Back Pain (CLBP) are two serious conditions affecting the lumbar spine, both often resulting in significant pain, decreased function, and poor treatment outcomes. There is growing consensus that plasma biomarkers could become clinically useful to better understand and treat these conditions. Nonetheless, the literature on plasma proteomics for these two conditions is lacking, and so is the understanding of what could be common pathways and shared contributing factors. This pilot comparative study used plasma proteomics analysis on two independent populations (one with LSS and one with CLBP) to explore significant similarities and differences in circulatory proteins.

Methods

Two independent sample cohorts were used (LSS; n=259 and CLBP; n=186) to select high clinically severe (HCS) subjects to compare against the less clinically severe (LCS) subjects. The comparison was done among the 2 groups within each cohort, and significant results were then compared between cohorts to highlight possible common proteins. Subjects were chosen based on VAS and ODI score

In the LSS population, participants in the LCS group (n=10) had a mean pain score (VAS) of 1.2 and Oswestry Disability Index (ODI) of 17.4.  The HCS group (n=10) consisted of subjects with mean VAS=8.4 and ODI= 57.8.  For the CLBP population, participants in the LCS group (n=18) had a mean pain score of 2.7 and an ODI mean of 13.6, while those in the HCS group (n=19) had a mean pain score of 7.7 and ODI mean of 49.4.

Differential Mass Spectrometry was performed on collected plasma. 385 plasma proteins were detected and quantified and compared between the two groups of the LSS population, while 377 proteins were quantified and compared between the two groups of the CLBP population. The relative abundance of these proteins was assessed using student’s t-test (Log2 transformed) with a p-value cut-off of 0.02.

Results

In the LSS samples, 11 plasma proteins were significantly elevated in the HCS group. In the CLBP sample, 31 plasma proteins were significantly elevated and 2 were significantly decreased in the HCS group. The only protein that was found to be significantly different in both populations (LSS and CLBP) was Factor 5 (F5), which was increased in the HCS group for both cohorts.

Discussion

Our finding is thought-provoking and unexpected. Interestingly, in addition to its role in the coagulation system, F5 is implicated in platelet degranulation, which is known to play a role in inflammatory responses and immune modulation. While there is an established body of evidence highlighting the relevance of inflammation in CLBP and LSS, research on F5 as an inflammatory mediator in these two conditions is lacking.

In conclusion, our study highlights a possible novel area of research to explore the potential role of F5 in LSS and CLBP both as a biomarker for clinical severity and as a potential shared mechanism.  Confirming the finding in larger cohorts and in association with other mediators of inflammation will be important to determine the significance of this finding.