Degenerative disc disease: a routine pathology with many unknowns (brief literature review)

Abstract

the human population. Its course is usually chronic and progressive, and the clinical correlate is pain. Despite such a concise portfolio, upon closer examination, it becomes clear that DDD is a conventional pathophysiological term without clear semantic limits. This type of pathology is often accompanied by more complex neurological symptoms, and etiology and pathogenesis of this pathology are poorly understood. Moreover, it remains unclear what is «normal aging» of the disc, and what is DDD. This article provides a synopsis of modern ideas about the morphology and physiology of human intervertebral discs (IVD) as well as the pathogenesis of DDD.From a perspective and practical point of view, for the laconic demonstration of the state of affairs in the DDD problem, we have chosen an apophatic method – the list of issues that need prior solving. Thus, there is no clear definition of DDD, comparison of clinical and pathomorphological characteristics of this pathology, and a clear understanding of its epidemiology. The exact composition and architecture of the intercellular matrix of IVD remain unknown, and ideas about the molecular mechanisms of its homeostasis are fragmentary. There is a lack of clarity regarding the mechanisms of the water-electrolyte balance of IVD, on which its biomechanical parameters depend. There is no satisfactory physicochemical model of the entry of metabolites into one or another part of the IVD, and ideas about the phenotype, features of vital activity, and regeneration of cell populations of the IVD are scant. The exact sources of the regional blood supply of the human IVD, and the peculiarities of the blood flow and angiogenesis in the IVD remain unclear. Similarly, there is no specific data on the sources of innervation of the human IVD, the phenotype of nerve fibers, and the molecular mechanisms of sensitization of IVD nociceptors. Concepts about the biomechanics of the lumbar spine, the role of different parts of the IVD in the transfer of axial load, and the values of this load according to the background of various motor activities of a person are minimal. There is a lack of empirical data on the harmfulness of prolonged sitting from the point of view of the development of DDD and the effectiveness of the relieving action of intra-abdominal pressure. The list of genetic variations and epigenetic factors that could cause DDD begins at the beginning of formation. Finally, the role of such phenomena as cellular epigenetic and transcriptomic regulation, oxidative stress and mitochondrial dysfunction of IVD cells, cellular senescence, apoptosis, autophagy, ferroptosis, necroptosis, pyroptosis and other types of cell death, as well as local immune reactions in IVD, mechanobiological properties of IVD cells, the role of systemic metabolic and vascular regulation in the pathogenesis of DDD, etc.It can be stated that DDD, being at first look a simple and population-routine disease with zero or casuistic level of mortality is a complex medico-biological phenomenon, which, given its dramatic prevalence, requires further careful study.