INTRODUCTION: While intervertebral disc degeneration (IDD) is implicated in LBP, the overlapping occurrence of IDD in symptomatic and asymptomatic individuals makes it challenging to identify the painful features provoking LBP.  It is thus prudent to examine the initiating mechanisms of LBP in individuals whose symptoms can be noninvasively induced and alleviated.  Standing induced LBP is common in young, back-healthy adults, and they experience sustained LBP symptoms after periods of prolonged standing (~2 hours). Pain-developers’ (PDs’) are three times more likely to experience a near-future bout of clinical LBP than non-pain developers (NPDs) [2]. We hypothesized NPDs and PDs exhibit differential adaptations of the IVD in prolonged standing, and the adaptations of the IVD are associated with the pain symptoms.

METHODS: 40 human back-healthy participants (; 18-30 yo; 21F, 19M) were recruited for a cross-sectional observational MRI study with approval by the Washington University SOM HRPO.  T2 weighted sagittal images were collected using a 0.6T pMRI [2]. Subjects were imaged after 15 minutes in the supine position, and for 105 minutes in the standing position in intervals of 15 minutes with reporting of pain severity using the Visual Analogue Scale (VAS) Those who reported sustained, non-zero pain at any time point were classified as PDs, else they were classified as NPDs.  The 3D structure of each of the five lumbar IVDs (L1L2 – L5S1) were characterized by measurements of each disc’s central height, major axis diameter, minor axis diameter, axis diameter ratio, whole disc (WD) volume, nucleus pulposus (NP) volume, NP volume fraction, intervertebral angle (IV Angle), and anterior-to-posterior height ratio (AP). The sagittal Cobb angle was measured at each time point. In the supine and initial standing positions, the degeneration grade was determined to consensus by two board-certified radiologists using a modified Pfirrmann scale. The ratio of the T2 signal intensity of the NP to the WD (NIDI) defined from the contoured segmentations. Analyses with temporally repeated measures were modeled using an autoregressive covariance structure [3]. 

RESULTS: WD volume was significantly reduced after standing in both males and females (p < 0.001, p < 0.05). The MRIs acquired in the supine or the initial standing positions were not sufficient to differentiate PDs from NPDs.   Comparing the changes from supine to initial standing, female PDs exhibited a significant reduction of NIDI (5.7%, p < 0.001).  Male PDs did not differ from NPDs. Pain status was a significant main effect on female disc height during prolonged standing, with female PDs exhibiting 7.8% reduction in disc heights compared to NPDs (p < 0.01).  Finally, we found that L3L4 and L4L5 morphologies are associated with pain in females, while L1L2 and L2L3 levels morphologies are associated with pain metrics in males (Table 1).

DISCUSSION: While male PDs could not be differentiated from NPDs, we identified the position- and level- specific IVD changes that predict the magnitude of pain in both males and females PDs.  The results here suggest that there may be sex-specific variations in the anatomical locations of the pain generator.