**4.1 Aetiology**

Most scientists regard osteoarthritis as an inflammatory process, being most frequent TMJ disorder, characterised with proliferative changes in the synovia and primary degeneration of the cartilage and surrounding tissues with destruction of the bone structures. (Holmlund & Axelsson, 1996; Emshoff , 2005). It is found that 28% of the adult population have signs of temporomandibular joint disorder. In systemic diseases (rheumatoid arthritis, psoriasis etc.) involvement of TMJ occurs (Voog et al., 2003b; 2004). Main aetiological factors of TMJ disorders are as follows: systemic diseases ( rheumatoid arthritis, psoriasis, pseudogout, ankylosing spondylitis etc.), secondary inflammatory component from the neighbouring regions (otitis, maxillary sinusitis, tonsillitis ), trauma (chronical), prevalence of dental arch defects e.g. missing of molar teeth, (Tallents et al. 2002), malocclusion, endocrinological disturbances, odontogenic infections (third molars). Presence of specific bacterial species as *Staphylococcus aureus, Streptococcus mitis, Mycoplasma fermentas, Actinobacillus actinomycetemcomitans (Aa)* in the synovial fluid have been found (Kim et al., 2003). Serum antibodies against *Chlamydia spp.* in patients with monoarthritis of the TMJ have been occurred. An association may exist between the presence of *Chlamydia trachomatis* and TMJ disease (Paegle et al., 2004).

## **4.2 Pathogenesis**

Knowledge about the pathogenesis on a molecular level of disorders of the TMJ has been improved in recent years giving a possibility to use these data for the evidence based treatment. Inflammation mainly affects the posterior disc attachement (Holmlund & Axelsson, 1996; Leibur et al., 2010). Several inflammatory mediators play an important role in the pathogenesis of TMJ diseases as tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), prostaglandin E2 (PGE2), leukotrien B4 (LkB4 ), matrix metalloproteinases (MMPs), serotonin- 5 hydroxytryptamine (5-HT), (Alstergren et al., 1999; Voog et al., 2003b). MMPs are responsible for the metabolism of extracellular matrix, being an early marker to determine TMJ arthritis. High level of MMP-3 has been determined in the synovial fluid in TMJ osteoarthritis patients (Kamada et al., 2000). Serotonin, mediator of pain and inflammation, is produced in the enterocromaffin cells of the gastrointestinal mucosa and absorbed by platelets. It is produced also in the synovial membrane and is present in the synovial fluid and in blood in case of rheumatoid arthritis and is involved in the mediation of TMJ pain in systemic inflammatory joint diseases (Alstergren & Kopp, 1997; Voog et al., 2000). It plays a role also in bone metabolism (Warden & Haney, 2008). Tissue response in case of inflammation is as follows: vasodilatation, extravasation, releasing of mediators, activation of nociceptors, release of neuropeptides as substance P (SP), neuropeptide Y (NPY), which stimulate releasing of histamin and serotonin from afferent nerve endings and hyperalgesia in TMJ occurs.
