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

Osteoarthritis and Cartilage Open (Sep 2022)

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

Affiliations

Starlee Lively: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada
Marie Milliot: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada
Pratibha Potla: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada
Osvaldo Espin-Garcia: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada; Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
Mehdi Layeghifard: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada; Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
Kala Sundararajan: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada
Helal Endisha: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada
Akihiro Nakamura: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada
Anthony V. Perruccio: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada; Institute of Health Policy, Management & Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
Christian Veillette: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada; Department of Surgery, Division of Orthopaedic Surgery, University of Toronto, ON, Canada
Mohit Kapoor: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada; Department of Surgery, Division of Orthopaedic Surgery, University of Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Corresponding author. Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, 5KD-426, 60 Leonard Avenue, Toronto, Ontario, M5T 0S8, Canada.
Y. Raja Rampersaud: Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada; Krembil Research Institute, University Health Network, Toronto, ON, Canada; Institute of Health Policy, Management & Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Corresponding author. Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, East Wing 1-441, 399 Bathurst Street, Toronto, ON, M5T 2S8, USA.

Journal volume & issue: Vol. 4, no. 3
p. 100283

Abstract

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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.

Published in Osteoarthritis and Cartilage Open

ISSN: 2665-9131 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the musculoskeletal system
Website: https://www.journals.elsevier.com/osteoarthritis-and-cartilage-open/

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