Uloga oksidativnog stresa i opiorfina u temporomandibularnim poremećajima

The role of oxidative stress and opiorphin in temporomandibular disorders

Temporomandibularni poremećaji (TMP) kronični su bolni poremećaji koji zahvaćaju čeljusni zglob, žvačne mišiće i okolna tkiva, s prevalencijom u populaciji od 3,6 do 7%. Patološki supstrat uglavnom izostaje, a uzrok je često nepoznat. Psihološki i mehanički stresni čimbenici mogu doprinijeti nastanku oksidativnog stresa (OS) i rezultirati TMP-om. Cilj je kvantificirati markere OS, totalni antioksidativni kapacitet (TAK) te nedavno izolirani endogeni peptid opiorfin (OP) u slini pacijenata s TMP-om i usporediti ih s kontrolnom skupinom. Kako kronična izloženost stresu može uzrokovati hiperalgeziju koja nastaje kao posljedica odgovora na stres u hipotalamičko-hipofizno-adrenalnoj (HHA) osi, cilj je istražiti ovaj mehanizam uspoređujući OP i markere OS s razinom salivarnog kortizola (SK). Hipoteze: OS ima ulogu u nastanku i održavanju TMP-a, stoga će markeri OS u slini rasti i/ili će se TAK smanjiti; opiorfin utječe na orofacijalne bolne sindrome kao što je TMP i njegove vrijednosti u slini će se razlikovati između bolesnika s TMP-om i kontrole. Poremećena HHA osovina je u podlozi povećanog OS i promjena razina OP u bolesnika s TMP-om. U 50 bolesnika s TMP-om (dijagnosticiranih pomoću kriterija i MRI nalaza) i 50 kontrolnih ispitanika sakupit će se slina. Za određivanje markera OS koristit će se ELISA sa spektrofotometrijom. Razine OP mjerit će se HPLC-MS/MS metodom koju smo sami razvili. Za određivanje SK koristit će se elektrokemiluminiscentna imunokemijska metoda s prethodnom ekstrakcijom. Pacijenti s TMP-om će biti randomizirani u 2 skupine (1:stabilizacijska udlaga + placebo tablete; 2:placebo udlaga + 1g vitamina C). Mjerenja će se ponoviti nakon 3 i 6 mjeseci. Praćenje OP, OS markera i SK tijekom tog razdoblja će, ovisno o promjenama simptoma TMP-a, dodatno rasvijetliti predloženi podliježeći mehanizam. Novi pristup u objašnjavanja neuroendokrinih mehanizama u TMP-u i uporaba sline kao neinvazivno pristupačne dijagnostičke tekućine predstavlja značajan napredak.

Temporomandibular disorders (TMD) are chronic painful conditions involving joints, masticatory muscles and associated tissues that affect 3.6-7% of the population. Observable pathology is mostly absent, and the cause is unknown. Psychological and mechanical stress factors could contribute to oxidative stress (OS) and lead to TMD. Aims are to quantify salivary OS markers and total antioxidant capacity (TAC) and to quantify recently isolated endogenous peptide opiorphin (OP) in saliva of TMD patients and compare them to controls. As chronic exposure to stress may cause hyperalgesia as a result of the stress response in the hypothalamic-pituitary-adrenal (HPA) axis, aim is to test this as an underlying mechanism by correlating OP and OS markers to salivary cortisol (SC) levels. Hypotheses: OS has a role in TMD onset and maintenance, thus salivary markers of OS will increase and/or TAC will decrease; OP influences orofacial pain syndromes, such as TMD, and its salivary level will differ between TMD patients and controls. Disbalanced HPA axis underlies the increase of OS and OP level changes in TMD patients. Saliva of 50 TMD patients (diagnosed by validated diagnostic criteria and MRI) and 50 controls will be collected. OS markers will be assessed by ELISA with spectrophotometric detection and by spectrophotometric reagent kits. OP levels will be measured by HPLC-MS/MS method, developed by team members. The electrochemiluminescence immunoassay ECLIA will be used for measuring SC. TMD patients will be randomized in 2 treatment groups (1:stabilization splint + placebo pills; 2:placebo splint + 1g of vitamin C). Measurements will be repeated after 3 and 6 months of treatment. Monitoring of OP, OS markers and SC during that period will, in relation to TMD symptoms changes, further elucidate underlying proposed mechanism. Novel approach to understanding neuroendocrine mechanisms in TMD and use of saliva as non-invasively available biofluid represent significant advances.

temporomandibularni poremećaji, oksidativni stres, opiorfin, orofacijalna bol, ELISA, HPLC MS, slina

temporomandibular disorders, oxidative stress, opiorphin, orofacial pain, ELISA, HPLC MS, saliva