1201 Investigating the Role of Sigma-1 Receptor Expression as an Origin for Discogenic Low Back Pain

INTRODUCTION: Despite the high prevalence of low back pain (LBP), identification of potentially modifiable pain generators remains a considerable challenge. Heightened expression of the Sigma-1 receptor (S1R) chaperone protein has been shown to modulate chronic pain in patients with hip/knee osteoarthritis, but has never been explored in degenerative spinal tissue. METHODS: Patients undergoing lumbar discectomy or interbody arthrodesis for discogenic LBP (with or without concomitant radiculopathy) were included. Inclusion criteria were: visual analog scale (VAS) pain scores =7, with type II or III Modic changes of the involved vertebral endplates, and Pfirrmann grade IV or V intervertebral disc degeneration on preoperative MRI. Fresh disc samples were sent for single-end RNA sequencing to quantify transcriptomic σ1R expression. Disc samples were grouped into elevated (=10 RPKM) or low (<10 RPKM) σ1R expression. Bivariate statistics were employed to identify differences in demographics, patient-reported outcome metrics (PROMs), and opioid consumption between groups. Linear regression analysis was used to explore the relationship between σ1R expression and baseline VAS while controlling for potential confounders. RESULTS: Fifteen disc samples were analyzed, with 7 exhibiting elevated σ1R levels. There were no significant differences in demographic variables or baseline analgesic intake between the two cohorts. Distribution of Modic changes was similar (p=0.71) between groups, while the elevated σ1R group had a greater proportion of patients with grade V Pfirrmann classification (85.7% vs. 12.5%, P = 0.018). Linear regression analysis revealed a significant association between S1R expression in the disc and greater baseline VAS pain scores (β=0.26, p=0.02). CONCLUSIONS: This study offers novel data suggesting the potential relationship between discogenic LBP and elevated σ1R at the tissue level. Further studies are needed to explore targeted therapeutic interventions against σ1R in the treatment of discogenic LBP.