Uloga oksidativnog stresa i opiorfina u temporomandibularnim poremećajima
Rostro-TMD
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 našeg kliničkog istraživanja 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 40 bolesnika s TMP-om (dijagnosticiranih pomoću DC/TMD protokola) i 40 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 razvili sami. Pacijenti s TMP-om će biti randomizirani u 2 skupine (1:stabilizacijska udlaga ; 2:placebo udlaga). Mjerenja će se ponoviti nakon 1., 3. i 6. mjeseca. 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 most common chronic orofacial pain conditions of non-dental origin, with prevalence in the general population of 3.6% to 7%. Despite signs and symptoms being well described in the literature, there is still an absence of underlying pathophysiological mechanisms. Evidence based strategies for diagnosis and management of temporomandibular pain still aren't available. Psychological and mechanical stress factors could contribute to oxidative stress (OS) and lead to TMD. Aim of our study is to quantify salivary OS markers and total antioxidant capacity (TAC), as well as recently isolated endogenous peptide opiorphin (OP), in 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. If decreased OP levels in TMD patients were encountered, we hypothesize that OP downregulation contributes to TMD onset as its analgesic effect is absent. Conversely, increased OP levels would suggest that OP is upregulated merely as a reaction to painful stimuli. Disbalanced SC levels in TMD patients would corroborate involvement of HPA axis in TMD mechanism, which is known to affect the intensity of OS. Saliva of 40 TMD patients (diagnosed by validated diagnostic criteria) and 40 controls will be collected. TMD patients will be randomized in 2 treatment groups (1: stabilization; 2: placebo splint). Measurements will be repeated after 1, 3 and 6 months of treatment. Monitoring of OP, OS markers and SC during that period will, depending on observed changes in TMD symptoms, further elucidate underlying proposed mechanism by performing multivariate analyses including treatment outcomes. This translational research aims to make basic science findings useful for clinical applications. Novel approach to understanding neuroendocrine mechanisms in TMD and their links to OS, as well and use of saliva as non-invasively available diagnostic biofluid represent significant scientific advances.
"The Role of Oxidative Stress and Opiorphin in Temporomandibular Disorders"
Temporomandibular disorders (TMD) are most common chronic orofacial pain conditions of non-dental origin, with prevalence in the general population of 3.6% to 7%. Despite signs and symptoms being well described in the literature, there is still an absence of underlying pathophysiological mechanisms. Evidence based strategies for diagnosis and management of temporomandibular pain still aren't available. Psychological and mechanical stress factors could contribute to oxidative stress (OS) and lead to TMD. Aim of our study is to quantify salivary OS markers and total antioxidant capacity (TAC), as well as recently isolated endogenous peptide opiorphin (OP), in 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. If decreased OP levels in TMD patients were encountered, we hypothesize that OP downregulation contributes to TMD onset as its analgesic effect is absent. Conversely, increased OP levels would suggest that OP is upregulated merely as a reaction to painful stimuli. Disbalanced SC levels in TMD patients would corroborate involvement of HPA axis in TMD mechanism, which is known to affect the intensity of OS. Saliva of 40 TMD patients (diagnosed by validated diagnostic criteria) and 40 controls will be collected. TMD patients will be randomized in 2 treatment groups (1: stabilization; 2: placebo splint). Measurements will be repeated after 1, 3 and 6 months of treatment. Monitoring of OP, OS markers and SC during that period will, depending on observed changes in TMD symptoms, further elucidate underlying proposed mechanism by performing multivariate analyses including treatment outcomes. This translational research aims to make basic science findings useful for clinical applications. Novel approach to understanding neuroendocrine mechanisms in TMD and their links to OS, as well and use of saliva as non-invasively available diagnostic biofluid represent significant scientific advances.
ISTRAŽIVAČKI PROJEKT HRVATSKE ZAKLADE ZA ZNANOST
ISTRAŽIVAČKI PROJEKT HRVATSKE ZAKLADE ZA ZNANOST
SVEUČILIŠTE U ZAGREBU, STOMATOLOŠKI FAKULTET
SVEUČILIŠTE U ZAGREBU, STOMATOLOŠKI FAKULTET