Association of presurgical circulating MicroRNAs with 1-year postsurgical pain reduction in spine facet osteoarthritis patients with lumbar spinal stenosis

Starlee Lively; Marie Milliot; Pratibha Potla; Osvaldo Espin-Garcia; Mehdi Layeghifard; Kala Sundararajan; Helal Endisha; Akihiro Nakamura; Anthony V Perruccio; Christian Veillette; Mohit Kapoor; Y Raja Rampersaud

doi:10.1016/j.ocarto.2022.100283

Association of presurgical circulating MicroRNAs with 1-year postsurgical pain reduction in spine facet osteoarthritis patients with lumbar spinal stenosis

Osteoarthr Cartil Open. 2022 Jun 3;4(3):100283. doi: 10.1016/j.ocarto.2022.100283. eCollection 2022 Sep.

Authors

Starlee Lively^{1

2}, Marie Milliot^{1

2}, Pratibha Potla^{1

2}, Osvaldo Espin-Garcia^{1

2

3

4}, Mehdi Layeghifard^{1

2

5}, Kala Sundararajan^{1

2}, Helal Endisha^{1

2}, Akihiro Nakamura^{1

2}, Anthony V Perruccio^{1

2

6}, Christian Veillette^{1

2

7}, Mohit Kapoor^{1

2

7

8}, Y Raja Rampersaud^{1

2

6}

Affiliations

¹ Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada.
² Krembil Research Institute, University Health Network, Toronto, ON, Canada.
³ Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
⁴ Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁵ Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁶ Institute of Health Policy, Management & Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁷ Department of Surgery, Division of Orthopaedic Surgery, University of Toronto, ON, Canada.
⁸ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Abstract

Purpose: Up to 30% of spine facet osteoarthritis patients with lumbar spinal stenosis (SF-OA + LSS) have little to no improvement in their pain after surgery. Lack of meaningful improvement in pain following surgery provides a unique opportunity to identify specific predictive biomarker signatures that might be associated with the outcomes of surgical treatment. The objective of the present study was to determine whether a microRNA (miRNA) biomarker signature could be identified in presurgical blood plasma that corresponded with levels of SF-OA + LSS patient post-surgical pain intensity one year later.

Methods: RNA was extracted from baseline plasma of SF-OA + LSS patients and prepared for miRNA sequencing. Statistical approaches were performed to identify differentially expressed miRNAs associated with reduced 1-year postsurgical pain (n = 56). Using an integrated computational approach, we further created predicted gene and pathway networks for each identified miRNA.

Results: We identified a panel of 4 circulating candidate miRNAs (hsa-miR-155-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-99b-5p) with higher levels at presurgical baseline that were associated with greater changes in % NPRS20Δ, reflecting reduced pain intensity levels at one year. Genes encoding hsa-let-7e-5p, hsa-miR-125a-5p, and hsa-miR-99b-5p are part of an evolutionarily conserved miRNA cluster. Using integrated computational analyses, we showed that mammalian target of rapamycin, transforming growth factor-β1 receptor, Wnt signaling, epithelial-mesenchymal transition regulators, and cholecystokinin signaling were enriched pathways of predicted gene targets.

Conclusions: Taken together, our findings suggest that 4 presurgical baseline circulating miRNAs correlate with 1-year postsurgical SF-OA + LSS patient pain intensity and represent possible candidate biomarker signature of surgical pain response.

Keywords: Lumbar spinal stenosis; Pain; Spine osteoarthritis; Surgery; miRNA.