RT-qPCR study of COX-1 and -2 genes in oral surgical model comparing single-dose preemptive ibuprofen and etoricoxib: A randomized clinical trialy.

BACKGROUND: This study aimed to evaluate the gene expression of cyclooxygenases (COXs) in an oral model of preemptive analgesia. MATERIAL AND METHODS: Gingival tissue was collected during extraction of lower third molars from a randomized, triple-blind, split-mouth and placebo-controlled study. The eligible patients were randomly sorted to receive a single dose either of ibuprofen 400mg, or etoricoxib 120 mg or a placebo, one hour prior to surgery. The temporal course of RNAm was evaluated for COX-1 and -2 by means of a quantitative polymerase chain reaction in real time (RT-qPCR) at time zero and 30 minutes after the surgical procedure began, and it was correlated with clinical parameters (pain and maximum mouth opening). RESULTS: There was a significant increase in COX-1 expression between T0 and T30 in ibuprofen (p=0.004) and etoricoxib (p=0.010) groups. As regards COX-2, there were increases from T0 to T30 in all groups (placebo, p=0.012; ibuprofen, p<0.001; etoricoxib, p<0.001). All groups showed a significant decrease in COX-2:COX-1 ratio from T0 to T30 (placebo, p=0.013; ibuprofen, p<0.001; etoricoxib, p=0.047). Experimental groups showed a significant correlation between COX-1 and COX-2 levels and clinical pain parameters. CONCLUSIONS: The present preemptive analgesia study concludes that COX-2 RNAm induction was directly linked to third molar-related tissue inflammation and that the relation between COX-1 and COX-2 levels were inversely proportional to the preemptively administered nonsteroidal anti-inflammatory drugs COX-2 selectivity. Key words:Preemptive analgesia, dental extraction, cyclooxygenases, real-time polymerase chain reaction.

Preemptive analgesia-related gene and protein expression in third molar surgeries under non steroidal anti-inflammatory drug protocols: A PROSPERO-registered systematic review of clinical studies

BACKGROUND: This study aimed to review translational studies focusing on third molar removal surgeries through a systematic analytical approach. MATERIAL AND METHODS: A PROSPERO-registered systematic review (CRD42017060455) was conducted following the PRISMA statement to summarize current knowledge on gene expression in third molar surgeries. A search was performed in PubMed's Medline and Scopus databases, without date or language restrictions, using the logical expression {[(Third molar) OR (preemptive) OR (cyclooxygenase inhibitors) OR (acute inflammation) AND (gene expression)]}. RESULTS: All studies included in the analysis evaluated gene expression in a third molar extraction model, using the preemptive analgesia methodology in seven investigations. The sample analyzed was obtained from gingival tissue biopsy (n=4), blood (n=1), transudate (n=1) and gingival tissue biopsy/transudate (n=1). There were differences with respect to evaluated genes, drug protocol, sample studied, and method for evaluating gene expression. CONCLUSIONS: Third molar surgeries were found to be associated with different COX-related gene expression patterns. Although inflammatory events following the surgical procedure are associated with COX isoforms, data from preemptive analgesia studies are scarce, especially from studies correlating gene expression and clinical parameters. In the future, from a clinical perspective, identifying the molecular targets of a drug based on individual gene expression may be helpful to delineate specific third molar, surgery-related, preemptive analgesia protocols

Dry Extract of Matricaria recutita L. (Chamomile) Prevents Ligature-Induced Alveolar Bone Resorption in Rats via Inhibition of Tumor Necrosis Factor-α and Interleukin-1ß.

BACKGROUND: Matricaria recutita L. (chamomile) has demonstrated anti-inflammatory activity. Accordingly, the ability of the Matricaria recutita extract (MRE) to inhibit proinflammatory cytokines and its influence on alveolar bone resorption (ABR) in rats. METHODS: Wistar rats were subjected to ABR by ligature with nylon thread in the second upper-left molar, with contralateral hemiarcade as control. Rats received polysorbate TW80 (vehicle) or MRE (10, 30, and 90 mg/kg) 1 hour before ligature and daily until day 11. The periodontium was analyzed by macroscopy, histometry, histopathology, and immunohistochemistry for the receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP). The gingival tissue was used to quantify the myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels by enzyme-linked immunosorbent assay. Blood samples were collected to evaluate bone-specific alkaline phosphatase (BALP), leukogram, and dosages of aspartate and alanine transaminases, urea, and creatinine. Aspects of liver, kidneys, spleen, and body mass variations were also evaluated. RESULTS: The 11 days of ligature induced bone resorption, low levels of BALP, leukocyte infiltration; increase of MPO, TNF-α, and IL-1ß; immunostaining increase for RANKL and TRAP; reduction of OPG and leukocytosis, which were significantly prevented by MRE, except for the low levels of BALP and the leukocytosis. Additionally, MRE did not alter organs or body weights of rats. CONCLUSION: MRE prevented the inflammation and ABR by reducing TNF-α and IL-1ß, preventing the osteoclast activation via the RANKL-OPG axis, without interfering with bone anabolism.