Abstract
Low back pain (LBP) is a prevalent symptom that more than 80% of the population experience once in their lifetime. This can lead to severe impairment of the workaday life and cause enormous costs in the society. Because LBP mostly appears as a non-specific back pain symptom, provoked by the spine or its environment, the evaluation of the source is bearing some challenge. Whereas the pathomorphological source of pain is well defined in the specific spinal pathology, such as in the case of a scoliosis or sciatica, finding a correlation between the source of pain and a certain abnormality is difficult in non-specific LPB symptoms. This is accompanied by the disadvantage of finding a suitable treatment. One possible source of LPB represents the intervertebral disc (IVD), which can alter from a pain free (asymptomatic) to a painful (symptomatic) IVD during degeneration, leading to so called discogenic back pain. Provocative discography is to date the only means to assign LBP to a degenerated disc, with its usage being under dispute. The IVD has an important function as a shock absorber, as there is a high load on the spine. During a lifetime, our IVD becomes degenerated which means its matrix is more catabolized then anabolized, leading to an overall matrix breakdown and decreased quality of the IVD. The matrix consists of long protein chains and sugars, responsible for the ability to attract water, comparable to a sponge. Due to the reduction and loss of these main components during degeneration, the IVD loses height and we get smaller during aging. This is a normal process which is pain free in most cases, meaning asymptomatic. But there is a certain subpopulation complaining about pain without showing any special pathomorphological changes. Thus far it was demonstrated that symptomatic degenerated IVDs produce more cytokines (IL-6, IL-8, IL-1, TNF-) and that these molecules are able to provoke pain sensation directly. The first part of this thesis aims to identify factors leading to a pro- inflammatory cascade in a degenerated IVD as well as the involved pathways. The matrix of the IVD consists of abundant structure proteins such as collagen or fibronectin as well as of a special sugar, the hyaluronic acid. During disc degeneration, these huge molecules become fragmented and catabolized. In this study we were able to show that hyaluronic acid fragments (fHA) provoked a pro-inflammatory and catabolic cascade in IVD cells in vitro. With gene silencing and inhibition of activity, we could detect TLR2 to be engaged in the up-regulation of IL-6 synthesis in fHA treated IVD cells.
Quero, Lilian