Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant disorder associated with chronic low back pain is intervertebral disc degeneration. There are twenty-three intervertebral discs in the human body, all located between vertebral bodies of the spine to impart flexibility, shock absorption, and load dissipation. Due to natural causes or traumatic events, the intervertebral discs can break down in a process known as disc degeneration. Coinciding degeneration, nerves can sprout into the intervertebral disc tissue where they are chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to study the pathomechanisms of pain and screen therapeutics.
While many research teams have created models of disc degeneration, the translation of these platforms to disc-associated pain models has been limited by inconsistent chronic pain-like behavior. Further, the few models which measure disc-associated pain have been established in mice, which are not amenable to surgical treatment procedures due to their small size. This deficiency has driven the need for a model of disc-associated pain where pain-like behavior is measurable in animals with intervertebral discs large enough for surgical procedures. These criteria promote rats as the optimal platform for a disc-associated model of chronic low back pain.
In this defense, a model of disc-associated pain will be described that exhibits chronic pain-like behavior, overt disc degeneration, and nerve sprouting in the intervertebral disc. In addition to the model, a novel method for measuring disc degeneration real-time, non-invasively, will be delineated which exhibits remarkable precision and accuracy. Finally, a next generation treatment, derived from decellularized, porcine nucleus pulposus tissue will be described which is injectable, thermally fibrillogenic, and cytocompatible. In our model of disc-associated pain, this biomaterial restores degenerated disc volume, dramatically decreases pain-like behavior, and returns disc mechanics to a quasi-healthy state.