Phenotypes of pathologic vertebral endplate degeneration

University Of California, San Francisco, San Francisco CA

Investigators

Linked publications, trials & patents

Abstract

Chronic low back pain (CLBP) is a significant cause of morbidity and societal expense. The intervertebral disc is thought to be a primary pain source, but mechanisms by which discs degenerate and hurt are poorly understood. Historical data suggest that the endplate can be a significant source of pain in some ?discogenic? patients due to pathological crosstalk between discs and adjacent vertebra. Further, our studies with NASA astronauts indicate that pathologic crosstalk is exacerbated by paraspinal muscle atrophy that alters spinal mechanics and endplate loading. Over the past funding period, we focused our efforts on developing new evidence for disc pain mechanisms, and based on these, advanced imaging tools that are sensitive and specific for low back pathology. We established imaging biomarkers for key aspects of pathologic crosstalk: 1) endplate damage (UTE MRI); bone marrow edema and paraspinal muscle atrophy (IDEAL MRI); and disc chemistry/infection (MRS). We also investigated cellular mechanisms by which crosstalk triggers vertebral bone marrow lesions (Modic changes; MC) that our data indicate are a common pain generator in CLBP patients. To further clarify the mechanisms and clinical relevance of endplate damage and MC, we now propose to characterize MC natural history in relation to etiology (inflammation versus infection) in an animals and humans. We will use our established imaging biomarkers to link architectural and biological data from MC induced in rats, to pain severity in association with MC progression and paraspinal muscle atrophy in humans. We will test the hypothesis that imaging biomarkers of endplate damage, disc chemistry, and muscle atrophy forecast MC progression and symptom severity. Three aims are proposed. In Aim 1 we will characterize MC mechanisms and natural history in relation to etiology (inflammation or infection) using a rat-tail model. In Aim 2 we will conduct a longitudinal study of CLBP patients to test the hypothesis that MC severity and progression is proportional to the extent of endplate damage (which facilitates crosstalk), and the presence of an adjacent ?Modic disc?, where ischemia drives the expression of inflammatory cytokines and pain-related factors (ischemic, sterile inflammation), or where inflammatory factors are upregulated by Propionibacteria acnes (infectious inflammation). In Aim 3 we will investigate the role paraspinal muscle atrophy toward exacerbating endplate damage, MC, and patient symptoms via altered segmental alignment (lordosis) and intersegmental mechanics (dynamic motion). Overall, we hypothesize that MC and symptom natural history will vary depending on both disc and paraspinal muscle condition - MC due to a sterile inflammation will resolve over time when paraspinal muscle quality is good. Alternatively, MC due to an infections stimulus will progress (since the underlying infection is ongoing). Through this work, we will validate an imaging suite that researchers can use to study the spine pathologies in clinical cohorts, and clinicians can use to localize pain generators, predict the future course of symptoms, and improve care of CLBP patients.