Serum and salivary inflammatory biomarkers in juvenile idiopathic arthritis-an explorative cross-sectional study.

BACKGROUND: Biomarkers may be useful in monitoring disease activity in juvenile idiopathic arthritis (JIA). With new treatment options and treatment goals in JIA, there is an urgent need for more sensitive and responsive biomarkers. OBJECTIVE: We aimed to investigate the patterns of 92 inflammation-related biomarkers in serum and saliva in a group of Norwegian children and adolescents with JIA and controls and in active and inactive JIA. In addition, we explored whether treatment with tumor necrosis factor inhibitors (TNFi) affected the biomarker levels. METHODS: This explorative, cross-sectional study comprised a subset of children and adolescents with non-systemic JIA and matched controls from the Norwegian juvenile idiopathic arthritis study (NorJIA Study). The JIA group included individuals with clinically active or inactive JIA. Serum and unstimulated saliva were analyzed using a multiplex assay of 92 inflammation-related biomarkers. Welch's t-test and Mann-Whitney U-test were used to analyze the differences in biomarker levels between JIA and controls and between active and inactive disease. RESULTS: We included 42 participants with JIA and 30 controls, predominantly females, with a median age of 14 years. Of the 92 biomarkers, 87 were detected in serum, 73 in saliva, and 71 in both biofluids. A pronounced difference between serum and salivary biomarker patterns was found. Most biomarkers had higher levels in serum and lower levels in saliva in JIA versus controls, and in active versus inactive disease. In serum, TNF and S100A12 levels were notably higher in JIA and active disease. The TNF increase was less pronounced when excluding TNFi-treated individuals. In saliva, several biomarkers from the chemokine family were distinctly lower in the JIA group, and levels were even lower in active disease. CONCLUSION: In this explorative study, the serum and salivary biomarker patterns differed markedly, suggesting that saliva may not be a suitable substitute for serum when assessing systemic inflammation in JIA. Increased TNF levels in serum may not be a reliable biomarker for inflammatory activity in TNFi-treated children and adolescents with JIA. The lower levels of chemokines in saliva in JIA compared to controls and in active compared to inactive disease, warrant further investigation.

Evidence for minimally invasive treatment-A systematic review on surgical management of disc displacement.

BACKGROUND: Surgical treatment of temporomandibular joint (TMJ) disc displacement (DD) has been established in different forms since over a century. Ther is a consensus to perform minimal invasive interventions as first-line surgical treatment since there are no evidence on best surgical practice yet. OBJECTIVE: The aim was to perform a complex systematic review (SR) on the topic-is there evidence for surgical treatment of TMJ DD? METHODS: The PICO was defined as DD patients (population), treated with different surgical interventions including arthrocentesis (intervention), compared with other or no treatment (control) regarding the outcome variables mandibular function, mouth opening capacity, TMJ pain, etcetera (outcome). For identification of prospective controlled trials and SRs, a search strategy was developed for application in three databases. RESULTS: The search yielded 4931 studies of which 56 fulfilled the stipulated PICO. Studies with low or moderate risk of bias were possible to include in meta-analyses. There were evidence suggesting arthrocentesis being more effective compared to conservative management (maximum interincisal opening (MIO): p < .0001, I2 = 22%; TMJ pain: p = .0003, I2 = 84%) and arthrocentesis being slightly more effective than arthrocentesis with an adjunctive hyaluronic acid injection (MIO: p = .04, I2 = 0%; TMJ pain: p = .28, I2 = 0%). Other treatment comparisons showed nonsignificant differences. The performed meta-analyses only included 2-4 studies each, which might indicate a low grade of evidence. CONCLUSION: Although arthrocentesis performed better than conservative management the findings should be interpreted cautiously, and non-invasive management considered as primary measure. Still, several knowledge gaps concerning surgical methods of choice remains.

Sick leave and disability pension among TMD patients with musculoskeletal diseases, mental and behavioural disorders - a SWEREG-TMD population-based cohort study.

BACKGROUND: Temporomandibular disorders (TMD) are associated with musculoskeletal diseases (MSD), mental and behavioural disorders (MBD), and patients with TMD have been shown to have 2-3 times more days of sick leave (SL) and disability pension (DP) than the general population. MSD and MBD are two of the most common causes for SL and DP, and the association between TMD and the influence of comorbidities on the need for SL and DP among TMD patients need further clarification. This study investigates the impact of MSD and MBD comorbidity on SL and DP among TMD patients diagnosed in a hospital setting and/or surgically treated. METHODS: All incident TMD patients diagnosed or treated in a hospital setting between 1998 and 2016 and aged 23-59 were included. A non-exposed comparison cohort was collected from the general population. The cohorts were grouped based on the presence of comorbidity: No comorbidity (Group I); MSD comorbidity (Group II); MBD comorbidity (Group III); and combined MSD and MBD comorbidity (Group IV). Main outcomes were mean annual days of SL and DP, and statistical analysis was conducted using generalized estimated equations. RESULTS: TMD subjects with no comorbidities (Group I) and with MSD/MBD comorbidity (Group II and III) were 2-3 times more often on SL and DP than the corresponding groups from the general population. However, in the group with both MSD and MBD comorbidity (Group IV), the difference between the TMD subjects and the general population was diminishing, suggesting an additive effect. CONCLUSION: TMD patients are more dependent on SL and DP benefits compared to general population and the difference remains even after considering MSD and MBD comorbidity. In individuals with combined MSD and MBD comorbidity, concurrent TMD has less impact on the need for social insurance benefits. The results accentuate the impact TMD has on the patients' impaired ability to return to work and why TMD should be recognized as having a substantial impact on individual and economic suffering as well as on societal costs, with emphasis on the influence of comorbidities on patient suffering.

Continued persistent facial pain despite several surgical interventions in the temporomandibular joint.

This article describes a woman in her forties who spontaneously developed facial pain 19 years after double-jaw orthognathic surgery. The focus of her pain was the left side of the face, including the temporomandibular joint (TMJ). Conservative treatment was initiated, including several occlusal splints, in addition to injections with local anesthesia, botulinum toxin, and corticosteroids, with limited effects. Surgical treatments with arthroscopy and discectomy, and ultimately a TMJ prosthesis, improved the patient's joint function but did not reduce pain. The question is whether the degenerated joint was due to progression of the original disease process or to multiple surgical procedures.

Diseases of the musculoskeletal system and connective tissue in relation to temporomandibular disorders-A SWEREG-TMD nationwide case-control study.

INTRODUCTION: Temporomandibular disorders (TMD) are comprised by a heterogenous group of diagnoses with multifaceted and complex etiologies. Although diseases of the musculoskeletal system and connective tissue (MSD) have been reported as risk factors for developing TMD, no nationwide population-based registry studies have been conducted to investigate this possible link. The aim of this study was to investigate the association between MSD and TMD in a population-based sample using Swedish registry data, and to further investigate the difference in such association between patients diagnosed with TMD in a hospital setting and patients surgically treated for the condition. MATERIALS AND METHODS: Population based case-control study using Swedish nationwide registry data. Data was collected between 1998 and 2016 from 33 315 incident cases and 333 122 controls aged ≥18, matched for sex, age, and living area. Cases were stratified into non-surgical (NS), surgically treated once (ST1) and surgically treated twice or more (ST2). Information on MSD exposure (ICD-10 M00-M99) was collected between 1964 and 2016. Odds ratios were calculated using conditional logistic regression, adjusted for country of birth, educational level, living area, and mental health comorbidity. RESULTS: A significant association between MSD and the development of TMD was found for all diagnostic categories: arthropathies (OR 2.0, CI 1.9-2.0); systemic connective tissue disorders (OR 2.3, CI 2.1-2.4); dorsopathies (OR 2.2, CI 2.1-2.2); soft tissue disorders (OR 2.2, CI 2.2-2.3); osteopathies and chondropathies (OR 1.7, CI 1.6-1.8); and other disorders of the musculoskeletal system and connective tissue (OR 1.9, CI 1.8-2.1). The associations were generally much stronger for TMD requiring surgical treatment. The diagnostic group with the strongest association was inflammatory polyarthropathies, M05-M14 (OR 11.7, CI 8.6-15.9), which was seen in the ST2 group. CONCLUSIONS: Patients with MSD diagnoses have a higher probability of being diagnosed with TMD, in comparison to individuals without MSD. This association is even stronger for TMD that requires surgery. The results are in line with earlier findings, but present new population-based evidence of a possible causal relationship between MSD and TMD, even after adjusting for known confounders. Both dentists and physicians should be aware of this association and be wary of early signs of painful TMD among patients with MSD, to make early referral and timely conservative treatment possible.

The Role of Mental Health and Behavioral Disorders in the Development of Temporomandibular Disorder: A SWEREG-TMD Nationwide Case-Control Study.

Purpose: There is a well-known association between mental and behavioral disorders (MBD) and temporomandibular disorder (TMD), although the association has not been established in population-based samples. This study aimed to investigate this relationship using national population-based registry data. Patients and Methods: This case-control study used prospectively collected data from Swedish national registries to investigate exposure to MBD and the probability of developing TMD in all Swedish citizens with hospital-diagnosed or surgically treated TMD between 1998 and 2016. Odds ratios were calculated using conditional logistic regression adjusted for educational level, living area, country of birth, musculoskeletal comorbidity, and history of orofacial/neck trauma. Results: A statistically significant association between MBD and TMD was found for mood affective disorders (OR 1.4), neurotic, stress-related and somatoform disorders (OR 1.7), behavioral syndromes associated with psychological disturbances and physical factors (OR 1.4), disorders of adult personality and behavior (OR 1.4), disorders of psychological development (OR 1.3), behavioral and emotional disorders with onset usually occurring in childhood and adolescence (OR 1.4), and unspecified mental disorder (OR 1.3). The association was stronger for TMD requiring surgery, with the strongest association in patients with disorders of psychological development (OR 2.9). No significant association was found with schizophrenia, schizotypal and delusional disorders, or mental retardation. Conclusion: The findings indicate an increased probability of TMD among patients with a history of certain MBD diagnoses, and a stronger association with TMD requiring surgery, specifically repeated surgery. This highlights the need for improved preoperative understanding of the impact of MBD on TMD, as TMD and chronic pain itself may have a negative impact on mental health.

Sick leave and disability pension in a cohort of TMD-patients - The Swedish National Registry Studies for Surgically Treated TMD (SWEREG-TMD).

BACKGROUND: Temporomandibular disorders (TMD) are common and affect approximately 10% of the adult population. TMD is usually associated with headache, pain in the masticatory muscles and/or the temporomandibular joint, clicking or crepitations during mandibular movement as well as painful and/or reduced mouth opening. This study aimed to investigate the level TMD-patients use social insurance benefits before and after their first time of diagnosis or first surgical event, compared to the general population. Furthermore, the aim was to investigate the differences in the use of social insurance benefits between surgically and non-surgically treated TMD-patients that were diagnosed in a hospital setting. METHODS: All Swedish citizens aged 23-59 diagnosed with TMD in a hospital setting and/or surgically treated for the condition during 1998-2016 were identified via the Swedish National Board of Health and Welfare. A non-exposed comparison cohort was collected via the Total Population Registry. Outcome and sociodemographic data were collected via Statistics Sweden. Main outcome was annual net days on sick leave and disability pension five years before (-T5) and five years after (T5) diagnosis and/or surgical treatment (T0). Regression analysis was conducted with generalized estimated equations. RESULTS: The study included 219 255 individuals (73% female) - 19 934 in the exposed cohort and 199 321 in the comparison cohort. The exposed group was classified into three subgroups: non-surgical, surgically treated once, and surgically treated twice or more. The mean annual net days of sick leave and disability pension combined during the ten-year follow-up was 61 days in the non-surgical group, 76 days in the surgically treated once group, and 104 days in the surgically treated twice or more subgroup. The corresponding number for the non-exposed comparison cohort was 32 days. CONCLUSION: Patients diagnosed with TMD in a hospital setting are 2-3 times more dependent on the use of social benefits than the general population. The reliance on sick leave and disability pension is seen as early as five years before diagnosis, and the reliance remains after surgical treatment. The reliance is stronger in patients with several surgical interventions. These findings indicate that patients diagnosed with TMD constitute a patient group with a high burden of health issues causing long-term dependence on social security benefits.

Neuropathic orofacial pain: Characterization of different patient groups using the ICOP first edition, in a tertiary level Orofacial Pain Clinic.

OBJECTIVE: To characterize patients with chronic neuropathic orofacial pain in accordance with the International Classification of Orofacial Pain (ICOP first edition) criteria. STUDY DESIGN: A retrospective chart review of 108 patients was conducted. The most common categories observed were trigeminal neuralgia (TN) (25.9%), burning mouth syndrome (BMS) (11.1%), persistent idiopathic facial pain (PIFP) (26.9%), and posttraumatic trigeminal neuropathic pain (PTTNP) (26.9%); 9.3% of patients could not be categorized. RESULTS: TN and BMS was more prevalent in the sixth decade, and PIFP and PTTN were more prevalent in the fifth decade. All categories showed female predilection. The pain in TN was predominantly episodic, described as "sharp shooting" and like an "electric shock," unilateral and affecting the V2 division, and with trigger zones in 50% of patients. Pain in BMS was predominantly constant and described as "burning," with the tongue being the most common site. Pain in PIFP and PTTNP was as follows: varied from constant to episodic; described as "burning," "sharp shooting," "throbbing," or "dull aching"; intraoral or extraoral; and mostly involving the V2 or V3 division. CONCLUSION: This study is the first to characterize patients with neuropathic orofacial pain using the new ICOP criteria. PIFP and PTTNP were most commonly misdiagnosed categories. Using diagnostic criteria will increase the understanding of this patient group.

Dual-crosslinked 3D printed gelatin scaffolds with potential for temporomandibular joint cartilage regeneration.

A promising alternative to current treatment options for degenerative conditions of the temporomandibular joint (TMJ) is cartilage tissue engineering, using 3D printed scaffolds and mesenchymal stem cells. Gelatin, with its inherent biocompatibility and printability has been proposed as a scaffold biomaterial, but because of its thermoreversible properties, rapid degradation and inadequate strength it must be crosslinked to be stable in physiological conditions. The aim of this study was to identify non-toxic and effective crosslinking methods intended to improve the physical properties of 3D printed gelatin scaffolds for cartilage regeneration. Dehydrothermal (DHT), ribose glycation and dual crosslinking with both DHT and ribose treatments were tested. The crosslinked scaffolds were characterized by chemical, mechanical, and physical analysis. The dual-crosslinked scaffolds had the highest degree of crosslinking and the greatest resistance to hydrolytic and enzymatic degradation. Compared to the dual-crosslinked group, the ribose-crosslinked scaffolds had thinner printed strands, larger pore surface area and higher fluid uptake. The compressive modulus values were 2 kPa for ribose, 37.6 kPa for DHT and 30.9 kPa for dual-crosslinked scaffolds. None of the crosslinking methods had cytotoxic effects on the seeded rat bone marrow-derived mesenchymal stem cells (rBMSC). After 4 and 7 d, the dual-crosslinked scaffolds exhibited better cell proliferation than the other groups. Although all scaffolds supported chondrogenic differentiation of rBMSC, dual-crosslinked scaffolds demonstrated the lowest expression of the hypertrophy-related collagen 10 gene after 21 d. The results show that 3D printed gelatin scaffolds, when dually crosslinked with ribose and DHT methods, are not toxic, promote chondrogenic differentiation of rBMSC and have potential application in tissue engineering of TMJ condylar cartilage.

Angiostatin-functionalized collagen scaffolds suppress angiogenesis but do not induce chondrogenesis by mesenchymal stromal cells in vivo.

Tissue engineering for fibrocartilage regeneration using mesenchymal stromal cells (MSC) and biomaterial scaffolds is emerging as a promising strategy, but inhibiting vascularization to prevent endochondral ossification is important to develop stable implants. The objective of this study was to investigate the effect of angiostatin on inhibition of angiogenesis and promotion of chondrogenesis by collagen scaffolds with or without MSC implanted subcutaneously in rats. One scaffold from the following groups was implanted in each animal: Collagen scaffolds only, scaffolds functionalized with angiostatin, scaffolds loaded with MSC and scaffolds functionalized with angiostatin and loaded with MSC. The various scaffolds were harvested after 2 and 8 weeks for histological analysis, Real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence quantification. Results demonstrated significantly decreased expression of inflammatory (interleukin 1 alpha and beta) and angiogenic genes (platelet and endothelial cell adhesion molecule 1) in scaffolds functionalized with angiostatin after 2 weeks in vivo. Histologically, after 8 weeks, the scaffolds with angiostatin had less inflammatory cells and more collagen matrix formation, but no fibrocartilage formation was detected. Thus, although angiostatin suppressed angiogenesis, it did not stimulate ectopic chondrogenesis in tissue engineered constructs in vivo.

Satisfactory outcomes after orthognathic surgery with surgically assisted rapid maxillary expansion using a hybrid device.

The self-reported functional outcomes, clinical findings, and results of dental cast analysis before and after orthognathic surgery with surgically assisted rapid maxillary expansion (SARME) using a hybrid rapid maxillary expander (RME) were evaluated. Data were collected from 43 patients who underwent orthognathic surgery with SARME using a hybrid RME between 2001 and 2013. The patients were recruited during a follow-up clinical examination and were required to complete a questionnaire about their opinions and self-reported functional outcomes. Dental casts were used to analyze posttreatment palatal expansion. The mean follow-up time was 68 months (range: 25-135 months). The most common indication for SARME was the presence of a crossbite. Of the 30 patients who underwent a follow-up clinical examination (69.8% answer rate), 4 (13.3%) had symptoms of temporomandibular disorder (TMD), 1 (3.3%) experienced myalgia, and 3 (10.0%) experienced arthralgia on clinical palpation. Cast analysis revealed significant palatal expansion. The intercanine distance, intermolar distance, and palatal height were increased by 3, 5, and 2 mm, respectively. Overall, the patients were satisfied with the preoperative information, improved functions, and aesthetic results. The prevalence of TMD symptoms and other side effects following orthognathic surgery with SARME using a hybrid RME was low, and significant palatal expansions were achieved.

Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial.

BACKGROUND: Autologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autologous bone grafting. This comprehensive clinical trial included subjects with severe mandibular ridge resorption. METHODS: The study included 11 subjects aged 52-79 years with severe mandibular ridge resorption. Bone marrow cells were aspirated from the posterior iliac crest and plastic adherent cells were expanded in culture medium containing human platelet lysate. The MSCs and biphasic calcium phosphate granules as scaffolds were inserted subperiosteally onto the resorbed alveolar ridge. After 4-6 months of healing, new bone formation was assessed clinically and radiographically, as were safety and feasibility. Bone at the implant site was biopsied for micro-computed topography and histological analyses and dental implants were placed in the newly regenerated bone. Functional outcomes and patient satisfaction were assessed after 12 months. RESULTS: The bone marrow cells, expanded in vitro and inserted into the defect together with biphasic calcium phosphate granules, induced significant new bone formation. The regenerated bone volume was adequate for dental implant installation. Healing was uneventful, without adverse events. The patients were satisfied with the esthetic and functional outcomes. No side effects were observed. CONCLUSIONS: The results of this comprehensive clinical trial in human subjects confirm that MSCs can successfully induce significant formation of new bone, with no untoward sequelae. Hence, this novel augmentation procedure warrants further investigation and may form the basis of a valid treatment protocol, challenging the current gold standard. TRIAL REGISTRATION: EudraCT, 2012-003139-50. Registered on 21 August 2013. ClinicalTrials.gov, NCT 02751125 . Registered on 26 April 2016.

How Far Have We Come in the Field of Nerve Regeneration After Trigeminal Nerve Injury?

Patients suffering from nerve injury with sensory disturbances or orofacial pain have greatly reduced quality of life, and it is a big cost for the society. Abnormal sensations caused by trigeminal nerve injury often become chronic, severely debilitating, and extremely difficult to treat. In general, non-invasive treatment such as drug treatment has been insufficient, and there are currently few available effective treatments. Surgical interventions such as end-to-end connection or nerve grafting have disadvantages such as donor site morbidity or formation of neuroma. There is need for optimizing the technique for nerve repair, especially for the trigeminal nerve system, which has so far not yet been well explored. Recently, tissue engineering using biodegradable synthetic material and cell-based therapies represents a promising approach to nerve repair and it has been reported that mesenchymal stem cell (MSC) has an anti-inflammatory effect and seems to play an important role in nerve healing and regeneration.

Implementation of a Web-Based Patient Simulation Program to Teach Dental Students in Oral Surgery.

The aim of this study was to evaluate a web-based simulation of patients (Web-SP) program on learning skills in clinical reasoning and patient evaluation in the oral surgery education of third-year dental students. A secondary aim was to investigate the program's effect on students' learning, knowledge, and attitudes towards virtual patient simulations. Authentic virtual oral surgery patient cases were created at a dental school in Sweden using the Web-SP platform. The Web-SP program was introduced in a two-hour seminar. A 20-minute pre-seminar test (test A) was administered to assess the students' knowledge of oral surgery prior to experiencing the Web-SP program. Ten days after the seminar, another test (test B) was administered to evaluate the increase in oral surgery knowledge as a result of using the program, and an emailed survey of the students was conducted. Of 70 students in the course, 67 (95.7%) agreed to participate in the study and took test A; of these, 59 (88%) took test B. Of the 59 students who took both tests, 28 (42%) completed the survey. The results of the two tests showed a statistically significant increase in knowledge, which was in accordance with the learning goals (p<0.0001). The survey results showed that the students had a positive attitude towards the teaching method. In this study, Web-SP was found to be a valuable tool for teaching clinical reasoning and patient evaluation in an undergraduate oral surgery education setting by improving learning outcomes in comparison with traditional teaching alone.

Reactive arthritis in relation to internal derangements of the temporomandibular joint: a case control study.

The aim of this study was to find out if reactive arthritis was involved in the aetiology of chronic closed lock of the temporomandibular joint (TMJ) by looking for bacterial antigens in the synovial membrane of the TMJ, and by studying the antibody serology and carriage of human leucocyte antigen (HLA) B27 in patients with chronic closed lock. Patients with reciprocal clicking and healthy subjects acted as controls. We studied a total of 43 consecutive patients, 15 with chronic closed lock, 13 with reciprocal clicking, and 15 healthy controls with no internal derangements of the TMJ. Venous blood samples were collected from all subjects for measurement of concentrations of HLA tissue antigen and serology against Chlamydia trachomatis, Yersinia enterocolitica, Salmonella spp., Campylobacter jejuni, and Mycoplasma pneumoniae. Samples of synovial tissue from patients with closed lock and reciprocal clicking were obtained during discectomy and divided into two pieces, the first of which was tested by strand displacement amplification for the presence of C trachomatis, and the second of which was analysed for the presence of species-specific bacterial DNA using 16s rRNA pan-polymerase chain reaction (PCR). There were no significant differences between the groups in the incidence of antibodies against M pneumoniae, Salmonella spp. or Y enterocolitica. No patient had antibodies towards C trachomatis or C jejuni. We found no bacterial DNA in the synovial fluid from any patient. The HLA B27 antigen was present in 2/15 subjects in both the closed lock and control groups, and none in the reciprocal clicking group. In conclusion, reactive arthritis does not seem to be the mechanism of internal derangement of the TMJ.

Expression of 5-HT3 receptors and TTX resistant sodium channels (Na(V)1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders.

BACKGROUND: Previous studies have shown that 5-HT3-antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. METHODS: Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. RESULTS: A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P < .001). CONCLUSIONS: This study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.

Increased ß-endorphin levels and generalized decreased pain thresholds in patients with limited jaw opening and movement-evoked pain from the temporomandibular joint.

PURPOSE: Patients with limited jaw opening and movement-evoked pain from the temporomandibular joint have moderate to severe pain that may be relieved by surgery. The purpose of this study was to investigate if the preoperative state is associated with alterations in plasma ß-endorphin (ßE) levels and pain thresholds. PATIENTS AND METHODS: Eighteen female patients with painful unilateral temporomandibular joint and 18 age-matched healthy women participated. After blood sampling for analysis of plasma ßE levels, pressure pain thresholds over the masseter muscles and index fingers were recorded with an electronic algometer. Electrical detection and pain thresholds were recorded with the PainMatcher (Cefar Medical AB, Lund, Sweden) device. Nonparametric statistics, ie, Mann-Whitney U test and Spearman correlation test, was used for statistical analyses. RESULTS: The patients showed higher plasma ßE levels (P = .013) and lower pressure pain thresholds over the masseter muscle at the painful side (P = .041) and bilaterally over the index fingers compared with the controls (P < .05 for all comparisons). High plasma ßE levels correlated to increased electrical detection thresholds (n = 36, r = 0.347, P = .038). CONCLUSIONS: This study showed that patients with limited jaw opening and movement-evoked pain from the temporomandibular joint had significantly higher plasma ßE levels and lower pressure pain thresholds in the orofacial area and at remote sites compared with pain-free, healthy, age-matched controls. An increased level of ßE seems insufficient to inhibit pain and central sensitization. Further studies are warranted to elucidate the relation between ßE and pain thresholds secondary to stress, inflammation, and discectomy.

Student perception of two different simulation techniques in oral and maxillofacial surgery undergraduate training.

BACKGROUND: Yearly surveys among the undergraduate students in oral and maxillofacial surgery at Karolinska Institutet have conveyed a wish for increased clinical training, and in particular, in surgical removal of mandibular third molars. Due to lack of resources, this kind of clinical supervision has so far not been possible to implement. One possible solution to this problem might be to introduce simulation into the curriculum. The purpose of this study was to investigate undergraduate students' perception of two different simulation methods for practicing clinical reasoning skills and technical skills in oral and maxillofacial surgery. METHODS: Forty-seven students participating in the oral and maxillofacial surgery course at Karolinska Institutet during their final year were included. Three different oral surgery patient cases were created in a Virtual Patient (VP) Simulation system (Web-SP) and used for training clinical reasoning. A mandibular third molar surgery simulator with tactile feedback, providing hands on training in the bone removal and tooth sectioning in third molar surgery, was also tested. A seminar was performed using the combination of these two simulators where students' perception of the two different simulation methods was assessed by means of a questionnaire. RESULTS: The response rate was 91.5% (43/47). The students were positive to the VP cases, although they rated their possible improvement of clinical reasoning skills as moderate. The students' perception of improved technical skills after training in the mandibular third molar surgery simulator was rated high. The majority of the students agreed that both simulation techniques should be included in the curriculum and strongly agreed that it was a good idea to use the two simulators in concert. The importance of feedback from the senior experts during simulator training was emphasised. CONCLUSIONS: The two tested simulation methods were well accepted and most students agreed that the future curriculum would benefit from permanent inclusion of these exercises, especially when used in combination. The results also stress the importance of teaching technical skills and clinical reasoning in concert.

Implant treatment without bone grafting in edentulous severely resorbed maxillas: a long-term follow-up study.

PURPOSE: To evaluate retrospectively the surgical outcome of tilted implants in severely resorbed edentulous maxillas as an alternative to bone grafting and the prosthodontic outcome of posterior extension bridges on tilted implants. PATIENTS AND METHODS: A total of 33 consecutive patients with severely resorbed edentulous maxillas participated in the study. In these patients, the maxillary bone volumes were insufficient for conventional placement of implants to support a fixed prosthesis. As an alternative to bone transplantation, a surgical technique with fenestration of the maxillary sinus to visualize the total amount of maxillary bone was used, followed by implant placement in a tilted manner along the anterior maxillary sinus wall. Thus, 4 to 6 implants of optimal length could be installed in each patient. Nineteen patients were included in this long-term follow-up study and were eligible for clinical evaluation at 8 to 12 years (mean, 10 years) after second-stage surgery. Each patient was examined clinically and radiographically. RESULTS: The 19 patients had a total of 103 implants. In 2 of these patients, 3 fixtures were lost during the first year after second-stage surgery. All other patients had all implants intact with functionally fixed dental prostheses, corresponding to a success rate of 97%. Radiographic examination showed bone resorption in 10% of the implants (10 implants in 5 patients with a total number of 27 implants), with a mean bone loss of 1.2 mm. Mucositis was seen in 47% of the patients. CONCLUSIONS: This long-term follow-up study (mean time, 10 years) demonstrates that patients with a severely resorbed maxilla can be treated successfully with conventional implant treatment. This simplified surgical technique can be an alternative to the more resource-demanding technique with bone grafting.