ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Arthritis, Experimental/prevention & control , Liver/drug effects , Quercetin/therapeutic use , Serum Albumin, Bovine/toxicity , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Arthritis, Experimental/chemically induced , Arthritis, Experimental/metabolism , Hyperalgesia/chemically induced , Hyperalgesia/metabolism , Hyperalgesia/prevention & control , Liver/metabolism , Male , Quercetin/pharmacology , Rats , Rats, Wistar , Synovial Membrane/drug effects , Synovial Membrane/metabolism , Treatment OutcomeABSTRACT
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.
Subject(s)
Arthritis, Experimental/immunology , Arthritis, Rheumatoid/immunology , Hyperalgesia/immunology , NF-kappa B/immunology , Temporomandibular Joint/immunology , Wnt Signaling Pathway , Animals , Arthritis, Experimental/pathology , Arthritis, Rheumatoid/pathology , Freund's Adjuvant , Hyperalgesia/pathology , Intercellular Signaling Peptides and Proteins/immunology , Interleukin-1beta/immunology , Lipids , Male , RANK Ligand/immunology , Rats, Wistar , Serum Albumin, Bovine , Synovial Membrane/immunology , Synovial Membrane/pathology , Temporomandibular Joint/pathology , Tumor Necrosis Factor-alpha/immunology , Wnt Proteins/immunologyABSTRACT
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 (pâ¯<â¯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 (pâ¯<â¯0.05). Increased CB1 immunofluorescent staining was observed in the neural tissues in the EA treated group in comparison with the other groups (pâ¯<â¯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.
Subject(s)
Bone Resorption/immunology , Bone Resorption/therapy , Electroacupuncture , Inflammation/pathology , Receptor, Cannabinoid, CB1/immunology , Receptor, Cannabinoid, CB2/immunology , Animals , Male , Periodontium/metabolism , Rats, Wistar , Trigeminal Ganglion/metabolismABSTRACT
Lymphoepithelial cyst is a rare lesion of the oral cavity, with the mouth floor being the most common site of occurrence. The therapeutic approach of choice is the surgical treatment, which has rare cases of postoperative complications. The aim of this study is to report the case of a 53-year-old patient who came to Dental Service in the Federal University of Ceará complaining of a small nodular lesion (0.5 cm) located in the ventral tongue. Excisional biopsy was performed and the surgical specimen was submitted for anatomopathological analysis, which found that there was an oral lymphoepithelial cyst. The patient returned after seven days for suture removal and reported loss of sensitivity around the ventral tongue. We prescribed Citoneurin for ten days; however, there was not any significant improvement of the sensitivity. Low frequency laser therapy sessions were applied. The only postoperative symptom was dysesthesia, where there is only a sensitivity decrease. Currently, the patient has a postoperative period of 1 year without recurrence of the lesion. Although previous reports have no described tongue sensorineural disorders associated with this lesion, the occurrence of this event may be related to an unexpected anatomical variation of the lingual nerve.