AbstractThe mechanisms underlying pain relief following spinal manipulative therapy (SMT) are not understood fully although biomechanical and neurophysiological processes have been proposed. As such, we designed this randomized trial to elucidate the contributions of biomechanical and neurophysiological processes. A total of 132 participants with low back pain were randomly assigned to receive SMT at either the lumbar segment measured as the stiffest or the segment measured as having the lowest pain threshold. The primary outcome was patient reported low back pain intensity following treatment. Secondary outcomes were biomechanical stiffness and neurophysiological pressure pain threshold. All outcomes were measured at baseline, after the fourth and final session and at 2-weeks follow-up. Data were analyzed using linear mixed models, and demonstrated that the SMT application site did not influence patient reported low back pain intensity or stiffness. However, a large and significant difference in pressure pain threshold was observed between groups. This study provides support that SMT impacts neurophysiological parameters through a segment-dependent neurological reflex pathway, although this do not seem to be a proxy for improvement. This study was limited by the assumption that the applied treatment was sufficient to impact the primary outcome.