Based on extensive research the anatomic components that have been considered to cause back pain include the intervertebral disks, paraspinal muscles, spinal ligaments, facet joint capsules, dorsal roots and dorsal root ganglia. While mechanical strain is an important causative factor in the initiation of spinal pain, biochemical irritation plays an important role in sensitizing nerve endings in the injured tissue. In addition, central sensitization at the spinal cord level can be an important contributor to persistent spinal pain. The mechanical input that results in back pain includes both acute mechanical loading and repetitive cyclic loading. The latter is particularly important in disc injury and degeneration and in muscle fatigue to the lumbar spine. In this chapter the biomechanics and neural mechanisms of thoracolumbar pain are described in the following order:​ (1) mechanisms of pain initiation and maintenance (nociceptive pain vs. neuropathic pain, acute vs. chronic pain, peripheral sensitization, central sensitization), (2) biomechanics of noxious loading of the thoraco-lumbar spine, (3) joint, ligament and skeletal pain (involving intervertebral disc, anterior and posterior longitudinal ligaments, ligamentum flavum, dura, facet joints, bone and periosteum), (4) neuropathic pain (involving nerve roots and dorsal root ganglia) and (5) muscle pain. Further research is required to better characterize the relationship between measured mechanical input to tissues of the spine and the molecular, histological and neurophysiologic outcomes that result in spinal pain. This understanding can help in the development of preventive strategies to reduce the risk of spinal injury and pain.