Summary Statement. Repetitive loading of degenerated human intervertebral discs in combined axial compression, flexion and axial rotation, typical of manual handling lifing activities, causes: an increase in intradiscal maximum shear strains, circumferential annular tears and nuclear seperation from the endplate. Introduction. Chronic low back pain (LBP) is a crippling condition that affects quality of life and is a significant burden to the health care system and the workforce. The mechanisms of LBP are poorly understood, however it is well known that loss of intervertebral disc (disc) height due to degeneration is a common cause of chronic low back and referred pain. Gross disc injury such as herniation can be caused by sudden overload or by damage accumulation via repetitive loading, which is a cause of acute LBP and an accelerant of disc degeneration. The aim of this study was to determine for the first time the relationship between combined repetitive compression, flexion and axial rotation motion of degenerated cadaver lumbar spine segments, and the progression of three-dimensional (3D) internal disc strains that may lead to disc herniation and macroscopic tissue damage. Patients & Methods. Seven degenerated human lumbar functional spinal units (FSUs) underwent pre-test MRI, had a grid of tantalum wires inserted into the mid-transverse plane of the disc and were subjected to 20,000 cycles of repetitive loading in combined compression (1.7 MPa), flexion (11–13°) and right axial rotation (2–3°) in a six degree of freedom hexapod robot. Stereoradiographs were taken at cyclic intervals (1, 500, 1000, 5000, 10000, 15000 and 20000 cycles) from which 3D intradiscal principal strains and maximum shear strains (MSS) were calculated and partitioned into nine disc anatomical regions. After testing the discs underwent post-test MRI followed by macroscopic assessment to identify tissue damage. A repeated measures ANOVA having a within-subjects factor of cycle number, and a between-subjects factor of disc region was used to examine the effects of cycle number and disc region on MSS. Results. No visible evidence of disc herniation occurred after 20,000 cycles, however circumferential annular tears and nucleus separation from the endplate were observed in all specimens in agreement with observed signal changes in post-test MRI images. There was a significant effect of both cycle number, disc region and the interaction of cycle number x disc region on MSS (p<0.001). MSS was significantly larger after 20,000 cycles compared with the first loading cycle in the anterior, left anterolateral, left lateral, and left posterolateral disc regions (p<0.037). Minor changes in MSS were seen in the posterior and nucleus regions. The largest increases were observed in the left anterolateral and left posterolateral regions after 20,000 cycles. Discussion/Conclusion. A significant increase in MSS was observed across most regions in the disc after 20,000 repetitive loading cycles, especially in the left anterolateral and left posterolateral regions. No herniation was observed, although macroscopic and MRI evidence of circumferential annular tears and nuclear separation from the endplate occurred, suggesting internal disc tissue disorganisation that may indicate a progression towards eventual herniation