Polysacharide of Agaricus blazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling.

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

Chenopodium Ambrosioides Linn Mitigates Bone Loss in Rats with Periodontitis.

Statement of the Problem: Periodontitis is an inflammatory disease that causes bone loss. Some patients do not respond well to the classic treatment and need therapies that minimize bone loss, the main sequel of the disease. Chenopodium ambrosioides L. has stood out due to its anti-inflammatory and anti-oxidative activities. However, no study has yet investigated its effect on periodontitis. Purpose: This study aimed to evaluate the bone protective effect of Chenopodium ambrosioides L. (CAL) extract on ligature-induced periodontitis model in rats. Materials and Method: For this, a pre-clinical assay was performed, using male Wistar rats divided into 3 groups: Naive (N) (n=6), not submitted to any procedure; Saline (SAL) (n=6), submitted to ligature-induced periodontitis and receiving 2 ml/kg of 0.9% saline solution; and CAL extract, which was subdivided into 3 subgroups (n=6/subgroup) receiving the CAL at 3 (CAL3), 10 (CAL10) or 30 mg/kg (CAL30). All agents were given, by oral gavage, 30 min before periodontitis induction and daily until euthanasia (11th day). By then, maxillae were removed for macroscopic, histological, and histometric analyses. Kidneys, liver, and stomach were collected to evaluate the safety of CAL extract. High-performance liquid chromatography (HPLC) assay was used to investigate the flavonoid content in the extract. Results: Chenopodium ambrosioides L. extract at 30mg/kg showed a reduction by 58% in bone loss marked by an increase (+35%) in the number of osteoblasts and a reduction (-51%) on the number of osteoclasts (p< 0.05). No significant alteration in the liver, kidney, or stomach was seen. Rutin was the main flavonoid found. Conclusion: In summary, it was observed that Chenopodium ambrosioides L. extract has shown important anti-inflammatory and bone anabolic and anti-resorptive properties without causing toxicity in the main organs. Rutin, as the main flavonoid of the extract, seems to be responsible for the beneficial effect of this agent.

Blockage of the fractalkine pathway reduces hyperalgesia and prevents morphological glial alterations-Comparison between inflammatory and neuropathic orofacial pain in male rats.

This study aimed to evaluate the effects of inhibitors of the fractalkine pathway in hyperalgesia in inflammatory and neuropathic orofacial pain in male rats and the morphological changes in microglia and satellite glial cells (SGCs). Rats were submitted to zymosan-induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P2 X7 antagonist, a cathepsin S inhibitor or a p-38 mitogen-activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6 h following arthritis induction or 7 and 14 days following nerve ligation. The expression of the receptor CX3 CR1 , phospho-p-38 MAPK, ionized calcium-binding adapter molecule-1 (Iba-1), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX3 CR1 and developed hyperalgesia and up-regulation of phospho-p-38 MAPK, which was prevented by all drugs (p < .05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba-1 was altered only in neuropathic rats (p < .05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (p < .05). All morphological alterations were reverted by modulating the fractalkine pathway (p < .05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p-38 MAPK and reverting morphological alterations in microglia and SGCs.

Through the fingers: Use of plastinated anatomical specimens for visually impaired students.

The plastination technique produces non-toxic human tissues, ensuring their safe handling in educational settings. This investigation aimed to understand if visually impaired students profit from the use of plastinated anatomical specimens in learning the anatomy of the nervous system. For this purpose, their learning performance was compared to sighted and blindfolded students recruited from three primary schools in Fortaleza city, in the state of Ceará. Initially, a questionnaire was applied before carrying out the pedagogical practice, followed by an anatomy lecture with practical components with the use of plastinated anatomical specimens and synthetic anatomical models of the nervous system. After these steps, the students answered the questionnaire previously applied. Our results showed that the tactile perception of the visually impaired participants was significantly more developed compared to sighted (p < 0.001) and the blindfolded (p < 0.0001) students. The average of correct answers in the reapplied questionnaire was higher in the groups that used plastinated specimens (p < 0.05). In conclusion, the use of plastinated specimens has proven to be an effective tool in promoting a better understanding of anatomical structures, mainly for students with or without visual impairments, making it a valuable asset in anatomy teaching.

Temporomandibular joint arthritis increases canonical Wnt pathway expression in the articular cartilage and trigeminal ganglion in rats.

The canonical Wnt pathway participates in inflammatory diseases and it is involved in neuropathic pain. This study evaluated the immunoexpression of the canonical Wnt signaling pathway in the articular cartilage of the temporomandibular joint (TMJ) and along the nociceptive trigeminal pathway in arthritic rats. For this, male Wistar rats were divided into Control (C) and Arthritic (RA) groups. Arthritis induction was performed through subcutaneous injection of methylated bovine serum albumin (mBSA) and complete Freund Adjuvant (CFA)/ Incomplete Freund Adjuvant (IFA) on the first 14 days (once a week), followed by 3 weekly intra-articular injections of mBSA (10 µl/joint; left TMJ). The following parameters were evaluated: nociceptive threshold, inflammatory infiltrate, type I and III collagen birefringence, immunohistochemistry for IL-1ß, TNF-α, IL-6, Wnt10b, ß-catenin, cyclin-D1 in articular cartilage, c-Myc in synovial membrane, and immunofluorescence analysis for c-Fos, Wnt-10b and ß-catenin in the trigeminal ganglion and the trigeminal subnucleus caudalis. The RA group showed intense articular cartilage damage with proliferation of type III collagen, increased immunoexpression of proinflammatory cytokines and Wnt-10b, ß-catenin and cyclin-D1 in the articular cartilage and c-Myc in the synovial membrane. In the RA group, a reduction in the nociceptive threshold was observed, followed by a significant increase in the expression of Wnt-10b in neurons and ß-catenin in satellite cells of the trigeminal ganglion. c-Fos immunoexpression was observed in neurons, peripherally and centrally, in arthritic rats. Our data demonstrated that TMJ arthritis in rats causes articular cartilage damage and nociceptive behavior, with increased immunoexpression of canonical Wnt pathway in the articular cartilage and trigeminal ganglion.

Oral carcinogenesis triggers a nociceptive behavior and c-Fos expression in rats' trigeminal pathway.

OBJECTIVE: To recognize changes that occur along the trigeminal pathway in oral cancer in order to establish an effective approach to pain control. METHODS: Wistar rats were divided into control and 4-NQO groups for 8, 12, 16, or 20 weeks. 4-NQO suspension was administered on the animals' tongues. Mechanical hyperalgesia, assessment of facial expressions, and an open-field test were performed. After euthanasia, the animals' tongues were removed for macro- and microscopic analysis. c-Fos expression was analyzed in the trigeminal pathway structures. RESULTS: 4-NQO induced time-dependent macroscopic lesions that were compatible with neoplastic tumors. Histopathological analysis confirmed oral squamous cell carcinoma in 50% of the animals on the 20th week. There was a significant nociceptive threshold reduction during the first two weeks, followed by a threshold return to the baseline levels, decreasing again from the 12th week. Facial nociceptive expression scores were observed on the 20th week, while increased grooming and exploratory activity were observed on the 8th week. Trigeminal ganglion showed an increased c-Fos immunoexpression on the 20th week, and in the trigeminal subnucleus caudalis, it occurred on the 16th and 20th. The long-term carcinogenic exposure caused changes in the nociceptive behavior and c-Fos expression in the rats' trigeminal pathway.

Botulinum Toxin in Facial Aesthetics Affects the Emotion Process: A Meta-analysis of Randomized Controlled Trials.

This study aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of the btulinum toxin-A (BT-A) in patiets with mood disorders. PubMed, Scopus, Web of Science, Cochrane Library and LILACS were searched without restrictions up to July 2022. The PICOS strategy was used for the selection of studies and risk-of-bias assessment was performed using Cochrane's tool for RCTs. RCTs were included if they compared BT-A treatment on facial muscles in patients with mood disorders to placebo. After assessment of the full texts, seven studies were selected. Five studies had low risk of bias for the generation of random sequence and blinding of participants and professional domains. A total of four studies showed a low risk of bias for the allocation concealment and blinding of the evaluation of the domain results. The domain of selective reports showed a low risk of bias in all included studies. However, four studies presented a high risk of bias for the domain of other biases. The meta-analysis was based on the mean difference or standardized mean difference between the BT-A and placebo groups for each selected trial and revealed that the BT-A group showed a significant improvement in the symptoms of depression when compared to placebo. This study revealed that the BT-A application into mimic muscles of the upper third of the face improves the mood disorders, but it was not possible to guarantee whether the aesthetic benefits can contribute to reducing the severity of the depressive state.

Teaching human anatomy to the visually impaired: A systematic review.

Information related to human anatomy is present throughout the educational process, especially in undergraduate courses in the biomedical area. These courses have complex theoretical and practical contents, and this becomes more evident when they are developed for the visually impaired. The objective of this work was to perform a systematic review on the teaching of human anatomy for the visually impaired. After the protocol was registered on the PROSPERO platform (CRD42022306002), 10 electronic databases were manually searched with the descriptors "teaching human anatomy" and "visually impaired." Intervention studies were selected without date or language restrictions. In the end, only eight studies were found. Tactile materials produced manually, and Braille and cadaveric pieces, are assessed as good tools for teaching human anatomy to the visually impaired. There is a pressing need for adaptations of teaching methods to make the teaching more accessible and inclusive.

Smartphone addiction in COVID-19 pandemic times: a longitudinal study with Brazilian dental students / Vício em smartphoneem tempos de pandemia por COVID-19: estudo longitudinal com estudantes de Odontologia

This study aimed to evaluate smartphone addiction, sleep quality, quality of life and depression among dental students before and during the first wave COVID-19 pandemic lockdown and explore how smartphone addiction influences the other variables. 57 dental students answered the smartphone addiction inventory, Pittsburg sleep quality index, WHOQOL-bref and research diagnosis criteria for temporomandibular disorders axis II questionnaires before and during lockdown. Statistical analysis was conducted using Wilcoxon test, Mann-Whitney U test, Spearman tests and linear regression models considering the smartphone addiction inventory total score as the independent variable. The high mean scores on smartphone addiction on both times are remarkable. The smartphoneaddictionprevalence was also high on both times (68.66% and 71.92% respectively). Overall sleep quality improved. However, there was no significant change on overall smartphone addiction, quality of life and depression grade during lockdown. Tolerance using smartphones increased during lockdown, especially for women. Smartphone addiction showed negative correlation to quality of life and positive correlation to depression, subjective sleep quality and sleep medication use. Smartphone addiction was apredictor to total WHOQOL-bref score, all WHOQOL-bref domains, sleep medication use and to depression on both times, before and during lockdown. Smartphone addiction was directly affecting quality of life. Despite the growing smartphone use among university students due to the pandemic restrictions, this study showed that the overall smartphone addiction, quality of life and depression grade were not influenced by the lockdown restrictions. However, it was observed an improvement on sleep quality during this period among dental students (AU).

O objetivo deste estudo foi avaliar o vício emsmartphones, qualidade de vida, qualidade de sono e depressão em estudantes de odontologia antes e durante a quarentena daprimeira onda da pandemia por COVID-19. 57 estudantes de odontologia responderam nos dois tempos os questionários validados:smartphone addiction inventory, índice de qualidade de sono de Pittsburg, WHOQOL-bref e critérios para diagnóstico em pesquisa dasdisfunções temporomandibulares eixo II. Foram realizados os testes estatísticos: Wilcoxon, Mann-Whitney U, Spearman e regressões lineares considerando o total do smartphone addiction inventorycomo variável independente. A prevalência de vício em smartphonesfoi elevada nos dois tempos (68.66% e 71.92% respectivamente). Durante a quarentena a qualidade de sono melhorou e não houve diferença estatisticamente significativa no vício em smartphones, qualidade de vida nem depressão. A tolerância no uso dossmartphonesaumentou, especialmente entre as mulheres. O vício em smartphonesapresentou correlação negativa com qualidade de vida e positiva com a depressão, qualidade subjetiva do sono e necessidade de medicação hipnótica. O vício em smartphonesfoi preditor para todos os domínios do WHOQOL-bref e seu escore total, para o uso de medicação e depressão em ambos os tempos. O vício em smartphonesfoi muito elevado nos dois tempos afetando a qualidade de vida dos estudantes. Apesar do aumento do uso desmartphonesem virtude das restrições impostas pela pandemia, esse estudo mostrou que o vício em smartphones, qualidade de vida e depressão não foram influenciados pela quarentena. Entretanto, foi observada melhora na qualidade de sono durante esse período (AU).

Anti-inflammatory and Hepatoprotective Effects of Quercetin in an Experimental Model of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the joints. Although methotrexate (MX) is the first-line treatment, side effects are common. This study aimed to investigate the effects of quercetin (QT) and/or MX on inflammation and systemic toxicity in a rat model of RA. Male Wistar rats were divided into control (C), RA, QT, MX, and QT + MX groups (n=6). The RA induction consisted of three intra-articular injections of methylated bovine serum albumin (1×/week) in the temporomandibular joint (TMJ). QT (25 mg/kg) and/or MX (0.75 mg) administration occurred by oral gavage daily. We performed mechanical hyperalgesia in TMJ, leukocyte recruitment in synovial fluid, histopathology, and immunohistochemistry (TNF-α, IL-17, and IL-10) in synovial membrane and toxicity parameters. The RA showed a reduction in the nociceptive threshold (p<0.001), increase in leukocyte recruitment in synovial fluid (p<0.001), intense inflammatory infiltrate (p<0.001), and intense immunoexpression of TNF-α, IL-17, and IL-10 in the synovial membrane (p<0.001) compared to C (p<0.001). QT and/or MX therapy reduced inflammatory parameters (p<0.001). However, downregulation of IL-10 was observed only in the groups that received MX (p<0.001). Leukocytosis was seen in RA (p<0.05), but QT and/or MX reversed it (p<0.05). MX was associated with pathological changes in the liver and higher levels of transaminases when compared to the other groups (p<0.05). QT co-administered with MX reversed this hepatotoxicity (p<0.05). There were no alterations in the kidney between the groups (p>0.05). QT has potential to support MX therapy, showing anti-inflammatory and hepatoprotective effects in this model.

Effects of low-level laser therapy on the orthodontic mini-implants stability: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to assess the effects of low-level laser therapy (LLLT) on the orthodontic mini-implants (OMI) stability. MATERIALS AND METHODS: An unrestricted electronic database search in PubMed, Science Direct, Embase, Scopus, Web of Science, Cochrane Library, LILACS, Google Scholar, and ClinicalTrials.gov and a hand search were performed up to December 2020. Randomized clinical trials (RCTs) or non-randomized clinical trials (Non-RCTs) that assessed the effects of LLLT on the OMI stability were included. Data regarding the general information, LLLT characteristics, and outcomes were extracted. The authors performed risk of bias assessment with Cochrane Collaboration's or ROBINS-I tool. Meta-analysis was also conducted. RESULTS: Five RCTs and one Non-RCT were included and 108 patients were evaluated. The LLLT characteristics presented different wavelength, power, energy density, irradiation time, and protocol duration. Five RCTs had a low risk of selection bias. Two RCTs had a low risk of performance and detection bias. All RCTs had a low risk of attrition bias, reporting bias and other bias. The Non-RCT presented a low risk of bias for all criteria, except for the bias in selection of participants. The meta-analysis revealed that LLLT significantly increased the OMI stability (p < 0.001, Cohen's d = 0.67) and the highest clinical benefit was showed after 1 (p < 0.001, Cohen's d = 0.75), 2 (p < 0.001, Cohen's d = 1.21), and 3 (p < 0.001, Cohen's d = 1.51) months of OMI placement. CONCLUSIONS: LLLT shows positive effects on the OMI stability.

Electroacupuncture Reduces Inflammation but Not Bone Loss on Periodontitis in Arthritic Rats.

Periodontitis and rheumatoid arthritis (RA) are inflammatory diseases characterized by chronic inflammation and bone erosion. Electroacupuncture (EA) shows anti-inflammatory and anti-resorptive effects in experimental periodontitis (EP) and in RA. It is important to investigate whether EA shows these effects in periodontal tissues in the presence of these two inflammatory diseases or not. For this, Wistar rats were divided into six groups: control (C); experimental rheumatoid arthritis (RA; bovine type II collagen-induced (CII)); experimental periodontitis (EP); RA/EP (RA + EP); EP/EA (EP treated with EA); RA/EP/EA (RA + EP treated with EA). EP was induced 21 days after RA induction and EA was performed previously and during the EP induction period, every 3 days until the 36th experimental day. The rats were euthanized on day 39. RA was evaluated by edema and the withdrawal threshold of hind paws. The maxillae were removed, and alveolar bone loss (ABL) and bone radiographic density (BRD) were evaluated. Immunohistochemical analyses for interleukins (IL)-6 and -17 and nuclear factor (NF)-κB were performed. Our results showed that EA reduced only the pain intensity in arthritic rats. Histomorphometric, macroscopic, and radiographic analyses did not show differences between the control and EP/EA groups. EA caused a reduction in ABL and BRD only in the presence of EP. EA caused a reduction in IL-6 and -17 in all groups, but NF-κB was only reduced in the arthritic rats with EP. In conclusion, EA reduced the inflammation related to periodontitis in arthritic rats but did not prevent ABL.

Bisphosphonate-related osteonecrosis induced change in alveolar bone architecture in rats with participation of Wnt signaling.

OBJECTIVE: This work aimed to study the role of inflammation in medication-related osteonecrosis of the jaw (MRONJ) in rats with focus on Wnt signaling. METHODS: A total of 36 female Wistar rats (12 weeks ± 200 g) were divided into 2 groups (n = 6) in 3 experiments: saline (SAL) and zoledronic acid (ZOL). For MRONJ induction, rats received 0.1 mg/kg of ZOL (ip) 3×/week for 9 weeks. Animals from the SAL group received 0.1 mg/kg of 0.9% SAL, ip 3×/week for 9 weeks. On the 8th week, 3 left upper molars were extracted, and on the 11th week, they were euthanized. Maxillae were evaluated by macroscopic and histopathological analyses; scanning electron microscopy (SEM); immunohistochemistry for DKK-1, Wnt 10b, and caspase-3; and Raman spectrometry. Gingiva was also collected for TNF-α e IL-1ß quantification. RESULTS: Bone necrosis was confirmed by healing impairment, reduced number of viable osteocytes, increased caspase-3 immunoexpression, and increased number of empty lacunae (p < 0.05). ZOL enhanced inflammation and increased gingival levels of IL-1ß and TNF-α (p < 0.05). Irregular indentations were seen on bone after ZOL administration. Bone necrosis was marked by reduced amount of total and type I collagen. ZOL reduced the mineral/matrix ratio and increased carbonate/phosphate ratio. It was observed a significant reduction on Wnt10b and beta-catenin immunolabeling in the bone tissue of ZOL group. CONCLUSION: In summary, MRONJ model caused bone necrosis due to intense inflammation. Wnt signaling seems to play an important role in this process. CLINICAL RELEVANCE: New therapeutic strategies focusing on Wnt pathway can provide an interesting approach for future treatments.

Immunoexpression of canonical Wnt and NF-κB signaling pathways in the temporomandibular joint of arthritic rats.

OBJECTIVE: To investigate the participation of canonical Wnt and NF-κB signaling pathways in an experimental model of chronic arthritis induced by methylated bovine serum albumin (mBSA) in rat temporomandibular joint (TMJ). MATERIALS AND METHODS: Wistar rats were sensitized by mBSA+Complete Freund Adjuvant (CFA)/Incomplete Freund Adjuvant (IFA) on the first 14 days (1 ×/week). Subsequently, they received 1, 2 or 3 mBSA or saline solution injections into the TMJ (1 ×/week). Hypernociceptive threshold was assessed during the whole experimental period. 24 h after the mBSA injections, the TMJs were removed for histopathological and immunohistochemical analyses for TNF-α, IL-1ß, NF-κB, RANKL, Wnt-10b, ß-catenin and DKK1. RESULTS: The nociceptive threshold was significantly reduced after mBSA injections. An inflammatory infiltrate and thickening of the synovial membrane were observed only after mBSA booster injections. Immunolabeling of TNF-α, IL-1ß and Wnt-10b was increased in the synovial membrane in arthritic groups. The immunoexpression of nuclear ß-catenin was significantly higher only in the group that received 2 booster TMJ injections. However, NF-κB, RANKL and DKK1 immunoexpression were increased only in animals with 3 mBSA intra-articular injections. CONCLUSION: Our results suggest that canonical Wnt and NF-κB signaling pathways participate in the hypernociception and inflammatory response in TMJ synovial membrane during the development of rheumatoid arthritis in rats.

Electroacupuncture increases immunoexpression of CB1 and CB2 receptors in experimental model of inflammatory bone loss.

This study evaluated the participation of CB1 and CB2 receptors in the antiresorptive effect of electroacupuncture (EA) on an experimental model of inflammatory bone loss in rats. 30 rats were divided into five groups: C (control); EP (experimental periodontitis); EA (C+ EA); EP-EA (EP+ EA in the acupoints LI4, LG11, ST36, ST44); EP - EA-sham (EP+ EA in sham acupoints). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. Animals were euthanized at day 11. Histometric analysis was performed to evaluate the percentage of bone area in the furcation area. Immunolabeling patterns in the periodontal tissues and immunofluorescent staining in the trigeminal ganglia and in the trigeminal spinal tract for CB1 and CB2 receptors were performed. It was observed increased bone loss in the furcation in the EP and EP-EA-sham groups, in comparison to the other groups (p < 0.05). Enhanced CB2 immunolabeling was observed in the periodontal tissues in the EP-EA group, when compared to the EP and EP-EA-sham groups (p < 0.05). Increased CB1 immunofluorescent staining was observed in the neural tissues in the EA treated group in comparison with the other groups (p < 0.05), while no expression of CB2 was observed in those regions. Our study showed that in the presence of inflammatory bone disease, EA treatment reduced bone erosion and increased the immunoexpression of CB1 in the neural tissues and CB2 in the periodontal tissues.

Inflammatory pain assessment in the arthritis of the temporomandibular joint in rats: A comparison between two phlogistic agents.

Temporomandibular joint (TMJ) disorders are a group of conditions that result in TMJ pain, which frequently limits basic daily activities. Experimental models that allow the study of the mechanisms underlying these inflammatory and pain conditions are of great clinical relevance. The aim of this study was to evaluate nociception, inflammation and participation of the macrophage/microglia cells in the arthritis of the TMJ induced by two phlogistic agents. 84 rats were divided into 2 groups: Zy, which received zymosan intra-articularly, or Cg, which received carrageenan intra-articularly. Mechanical nociception, total leukocyte influx to the synovial fluid and histopathological analyses were evaluated in the TMJ. The participation of macrophage/microglia located in trigeminal ganglia (TG) and in the subnucleus caudalis (V-SnC) was assessed immunohistochemically. Both agents induced mechanical hyperalgesia 6h after the induction, but a more persistent algesic state was perceived in the Cg group, which lasted for 120h. Even though both groups presented increased leukocyte influx, the Zy-group presented a more intense influx. Zymosan recruited resident macrophage in the trigeminal ganglia 24h after the injection. In the V-SnC, the group Cg presented a more prolonged immunolabeling pattern in comparison with the group Zy. It can be concluded that zymosan induced a more intense infiltrate and peripheral nervous changes, while Cg lead to a moderate TMJ inflammation with prominent changes in the V-SnC.

Antinociceptive and anti-inflammatory effects of Caryocar coriaceum Wittm fruit pulp fixed ethyl acetate extract on zymosan-induced arthritis in rats.

The ethyl acetate extract from the fruit pulp of Caryocar coriaceum Wittm (Caryocaraceae), popularly known as pequi, has wide applications in popular medicine. Preclinical tests have demonstrated the therapeutic properties of the oil. We investigated the antinociceptive and anti-inflammatory effects of Pequi C. coriaceum Wittm ethyl acetate extract (PCCO) on zymosan-induced arthritis in rat knee joint. The animals were pretreated with PCCO for 7 consecutive days or with a single dose. Paw elevation time (PET), leukocyte infiltration, myeloperoxidase activity (MPO) and cytokine levels were assessed 4h after zymosan injection. Synovial tissue was harvested for immunohistochemical analysis, edema and vascular permeability. We observed a significant decrease in PET with PCCO pretreatment. PCCO showed a significant reduction of leukocyte migration and a decrease in MPO. Decreases were observed in cytokine release in the synovial fluid and TNF-α and cyclooxygenase-1 immunostaining in synovial tissue. Edema was inhibited by treatment with all doses of PCCO. The data suggest that PCCO exerts antinociceptive and anti-inflammatory effects on arthritis in rats.

Effects of nonsteroidal anti-inflammatory drugs on osseointegration: a review.

The purpose of this study was to review the effects of nonsteroidal anti-inflammatory drugs on osseointegration and determine whether they cause failures in dental implants and whether patients who use them chronically can receive dental implants safely. A bibliographic electronic search was performed using the Cochrane Library, PubMed, and Medline databases, selecting articles published between January 1982 and December 2012. The search included the following keywords, either alone or combined: "nonsteroidal anti-inflammatory drugs," "dental implants," "bone healing," and "osteoprogenitor cells." The inclusion criteria were the following: randomized, double-blind, placebo-controlled clinical studies, in vivo animal model studies of osseointegration, and in vitro studies of the effects of these agents on osteoprogenitor cells. The literature search revealed 360 references. A total of 31 articles met the inclusion criteria, including 2 clinical trials, 20 animal studies, and 9 osteoprogenitor cell studies. The clinical trials revealed that cyclooxygenase-1 (COX-1) inhibitors did not impair osseointegration. The animal studies showed that any drug that is capable of inhibiting COX-2 may impair the osseointegration process. The in vitro studies showed that COX-2 inhibitors are the most potent depressors of osseointegration at the cellular level. Caution must be taken when selecting COX-2 nonsteroidal anti-inflammatory drugs during the postoperative period.

Effects of electroacupuncture on experimental periodontitis in rats.

BACKGROUND: Acupuncture has shown the capability of modulating the immuno-inflammatory response of the host. This study aims to evaluate the effects of electroacupuncture (EA) on ligature-induced periodontitis in rats. METHODS: Thirty-two animals were divided into four groups: 1) control; 2) experimental periodontitis (EP); 3) sham-treated (EP/EA-sham); and 4) treated with EA (EP/EA). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. For EA treatment, large intestine meridian points LI4 and LI11 and stomach meridian points ST36 and ST44 were used. EA-sham was performed in off-meridian points. Animals were euthanized at day 11. Histomorphometric and microtomographic analyses were performed. Immunolabeling patterns for the receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) were assessed. Expressions of interleukin (IL)-1ß, matrix metalloproteinase (MMP)-8, IL-6, and cyclooxygenase (COX)-2 messenger RNAs (mRNAs) were evaluated by quantitative reverse transcription-polymerase chain reaction. Data were analyzed statistically (P <0.05, analysis of variance). RESULTS: Histomorphometric and microtomographic analyses demonstrated that group EP/EA presented reduced alveolar bone loss when compared to group EP (P <0.05). Reduced RANKL immunolabeling and fewer TRAP-positive multinucleated cells were observed in the EA-treated group in relation to group EP. No differences were observed in OPG expression among groups. EA treatment decreased the genic expression of IL-1ß and MMP-8 (P <0.05), increased the mRNA expression of IL-6 (P <0.05), and did not modify the genic expression of COX-2 in animals with EP (P >0.05). CONCLUSION: It can be concluded that EA reduced periodontal tissue breakdown and the expression of some proinflammatory mediators and a proresorptive factor in EP in rats.

Role of NMDA receptors in the trigeminal pathway, and the modulatory effect of magnesium in a model of rat temporomandibular joint arthritis.

Temporomandibular joint (TMJ) arthritis is a common cause of orofacial pain. In the present study, the modulatory effects of N-methyl-d-aspartate receptors (NMDA-Rs) and magnesium were investigated in TMJ arthritis hypernociception. Male Wistar rats received an intra-articular injection of carrageenan (Cg) in the TMJ, and mechanical hypernociception was measured. The NMDA-R antagonist, MK-801, and magnesium chloride (MgCl2 ) were administered before arthritis induction. Magnesium deficiency was promoted by feeding rats a synthetic magnesium-free diet for 9 d before injection of Cg. The Cg induced mechanical hypernociception that lasted for 120 h. MK-801 inhibited this hypernociceptive state. MgCl2 pretreatment prevented Cg-induced hypernociception and altered the nociceptive threshold in the absence of Cg. Magnesium deficiency increased hypernociception and induced spontaneous hypernociceptive behavior. TMJ arthritis increased the expression of mRNA for all NMDA-R subunits and immunostaining of phosphorylated NR1 (phospho-NR1). MgCl2 inhibited expression of NR2B mRNA and phospho-NR1 immunostaining and increased expression of NR3 mRNA. Magnesium deficiency increased expression of both NR1 and NR3 mRNAs and phospho-NR1 immunostaining in the trigeminal subnucleus caudalis. We found that magnesium modulates nociceptive behavior and induces NMDA-R subunit rearrangement in the subnucleus caudalis. The present results may lead to a better understanding of central processing in the nociceptive trigeminal pathway and the development of new approaches to treat orofacial pain with a TMJ origin.