Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2011; 15: 1296-1300 Combined occlusal and pharmacological therapy in the treatment of temporo-mandibular disorders F. INCHINGOLO 2, M. TATULLO 3,4 , M. MARRELLI 3, A.M. INCHINGOLO 6, A. TARULLO 5, A.D. INCHINGOLO 5, G. DIPALMA 3, S. PODO BRUNETTI 1, A. TARULLO 1, R. CAGIANO 1 1Department of Biomedical Sciences and Human Oncology, Toxicology Unit, University of Bari, Bari (Italy) 2Department of Dental Sciences and Surgery, University of Bari, Bari (Italy) 3Department of Maxillofacial Surgery, Calabrodental, Crotone (Italy) 4Department of Medical Biochemistry, Medical Biology and Physics, University of Bari, Bari (Italy) 5Dental School, School of Medicine, University of Bari, Bari (Italy) 6Dental School, School of Medicine, University of Milan, Milan (Italy) Abstract. – Objective: Aim of the present be guessed by the wide range of terms used over work is to assess the effectiveness of a scientif - the years to point out the alterations of the masti - ic protocol built up to relieve pain in chronic catory system, creating further confusion in a temporo-mandibular disorders (TMD) using field characterized by an interesting and wide Michigan splint together with a pharmacological multiplicity of nuances 1,2 . Nowadays, the term therapy compared to the traditional occlusal Temporo-Mandibular Disorder (TMD) is general - thePratpiyenbtys: Michigan splint alone. 35 adult patients, with signs and symp - ly used. It includes all the alterations connected to toms of TMD lasting more than 6 months, were en - the function of the entire masticatory system. Re - rolled into this study and divided into two groups: cently, epidemiological studies indicate that the first receiving occlusal therapy by Michigan around 60% of the total population shows splint and pharmacological therapy with Delo - myoarthropathy symptoms. In particular, the razepam and Thiocolchicoside, while the second re - ceiving occlusal therapy by Michigan splint and prevalence of symptoms seems to be around 59%, “placebo” administration. The comparisons be - while the prevalence of signs reaches almost the tween the two experimental groups were assessed 80% of the total population. This high prevalence usiRngesau5ltsstepasnvdisuCaol-nancalulosgiuoenssc: ale (V.A.S.). highlights a clear picture of their wide spread dif - The outcomes fusion, although this is certainly due to the inclu - from the experimental groups were statistically sion, in many scientific works, of signs and compared resulting significantly different with symptoms of little importance 3-11 . The Michigan an improvement or disappearance of signs and symptoms in the treated group with respect to splint is a removable appliance frequently used in the placebo group at 12 and 1p8 months from the the treatment of patients with TMD and related beginning of the experiment ( < 0.001). diseases, such as tensive headache. Key Words: The aim of the present study is to assess the effectiveness of a new protocol built up to relieve TMDs, Combined occlusal and pharmacological ther - pain with pharmacological treatment of chronic apy, Michigan splint, Delorazepam, Thiocolchicoside. TMD, compared to the traditional occlusal thera - py protocol by Michigan splint without effective pharmacological therapy. Introduction Materials and Methods The term myoarthropathy of the masticatory system refers to a large number of pathologic 35 patients were enrolled in this study, 21 conditions affecting the masticatory musculature women (40 ± 10 years old) and 14 men (30 ± 5 and/or the Temporo-Mandibular Articulation years old), who were diagnosed for TMDs; clin - (TMA). The complexity of this subject matter can ical criteria were palpation-related pain and Corresponding Author: Raffaele Cagiano, MD; e-mail: [email protected] 1296 Combined occlusal and pharmacological therapy in the treatment of temporo-mandibular disorders cy of its chloride ion channel resulting in the therapeutic benzodiazepines actions 13 . Thiocolchicoside Thiocolchicoside is a muscle relaxant with an - ti-inflammatory and analgesic effects. It acts as a competitive GABA-A receptor antagonist and al - so inhibits glycine receptors with similar potency and nicotinic acetylcholine receptors to a much lesser extent. It has powerful convulsant activity and should not be used in seizure-prone individu - als. It is a natural glucoside of colchicum without curare-like effects. Thiocolchicoside does not al - terate voluntary motility and does not interfere with respiratory muscles. It has no valuable ef - fects on the cardiovascular system. Instrumental examinations were performed by panoramic X-ray (OPT) and magnetic resonance of the TMA. A visual-analogue scale (V.A.S.) 14 was used in order to evaluate the intensity pain referred by patients consequent to palpation (Table I). The first group (treated group = 19 patients) re - ceived an occlusal therapy with “ Michigan splint ” (Figure 3) and pharmacological therapy with “de - lorazepam drops” and “thiocolchicoside tablets”. Figure 1. Palpation of the masticatory muscles. The second group (placebo group – 16 patients) received occlusal therapy with “Michigan splint” and “Placebo” administration: tablets and drops, clicking or limited mouth opening. The clinical diagnosis of TMDs was based on a patient symptom questionnaire including intra -oral and extra -oral muscle examination (Figure 1). All patients were examined by the same investiga - tor in order to avoid any kind of bias. Further - more, all subjects signed an informed consent form confirming their voluntary participation in this study. During the objective exams, all pa - tients referred spontaneous and palpation-relat - ed pain (Figure 2). Used Drugs Delorazepam Delorazepam (Chlordemethyldiazepam) is a long acting benzodiazepine with anxiolytic, hyp - noinducing, myorelaxant and anticonvulsant ac - tivities. It is considered a short-acting benzodi - azepine drug which exerts both therapeutic and adverse effects linking with high affinity to GABA A receptor sites in the central nervous sys - Figure 2. 12 Magnetic Resonance of the TMA of a patient be - tem enhancing the effects of GABA at the fore our therapy. Anterior subdislocation of the right TMA’s GABA A receptor increasing the opening frequen - meniscus. 1297 F. Inchingolo, M. Tatullo, M. Marrelli, A.M. Inchingolo, A. Tarullo, A.D. Inchingolo, et al. Table I. Visual-analogue scale. The greatest No Mild Troublesome imaginable pain pain pain Intense pain pain 001212 33445 5 6677 89 8 9 10 prepared by a pharmacist, were similar to those and Wednesday on the 2nd week, Sunday, Tues - used in the first group, but without the active drugs. day and Friday on the 3rd week, Sunday, Tues - Patients were asked to express their pain inten - day Thursday and Saturday on the 4th week and sity marking a point on a straight line, whose left wearing it only on Sunday for the next 2 weeks. limit was 0 (corresponding to absence of pain ) The remaining period of time (6 weeks) was con - and right limit was 10 (corresponding to the sidered necessary for a full wash-out from phar - greatest imaginable pain ). The VAS data were macological treatment. collected at T 0 and after 6 (T1), 12 ( T2) and 18 Statistical Analysis months (T max ) from the beginning of treatment . Data collected from the experimental group V.A.S. data were statistically evaluated using treated with “Michigan splint” and “delorazepam Unpaired t-test . Analysis of variances was fur - and thiocolchicoside” were compared with data ther performed with a nonparametric test. p value collected from experimental group treated with was statistically significant when < 0.05. occlusal therapy and “Michigan splint” alone. Furthermore, regarding the occlusal therapy, pa - Results tients were asked to wear their splint overnight along the first 12 months, positioned on superior arch. About the pharmacological therapy, the daily Comparisons between VAS values of the two dose used were: experimental groups (Unpaired t-test) before to • Delorazepam drops, 1 mg/day (12 drops/day) begin the treatment, gave not significant results along 12 months, decreasing 1 drop every month (p=0.2990) (two-tailed p=0.6479, t=0.461; up to 1 drop/day during the whole 12 th month ; df=33) allowing us to proceed . • Thiocolchicoside, 1 tablet 4 mg/12 hours along VAS values of the two experimental groups 12 months . were further compared: Soon after the 12 months treatment, all pa - tients were asked to gradually discard their splint At 6 months from the beginning of the treatment, the not wearing it on Sunday in the 1st week, Sunday comparisons between VAS values of the two experi - mental groups gave the following results: (two-tailed p < 0.0088; t=2.785; df=33); F test comparing vari - ances gave no significant results (F=1.739; DFn=18; Dfd=15; n.s.) ; At 12 months from the beginning of the treat - ment, VAS data comparisons gave significant results (two tailed p < 0.0001 ; t=7.728; df=33); F test comparing variances (F=3.343; DFn=18; Dfd=15; p < 0.0112); At 18 months from the beginning of the treat - ment , VAS data comparison also gave signifi - cant results (two-tailed p < 0.0001); t=9.041; Figure 3. df=33). F test comparing variances (F= 4.754; Michigan splint. DFn=18; Dfd=15; p < 0.0019). 1298 Combined occlusal and pharmacological therapy in the treatment of temporo-mandibular disorders Some patients regularly using the Michigan occlusal problems, they were considered the only splint (28 patients=80%) declared