Clinical Pharmacogenetic of ibuprofen enantiomers after lower third molar surgeries

Abstract

The non-steroidal anti-inflammatory drugs (NSAIDs) are an over the counter drug, which is frequently consumed by population in order to control even chronic and acute pain after inflammatory processes. This class of drugs, despite the long literature involved, still need to be more understood by clinicians all over the world. One of the preconized models in order to evaluate this class of drugs effects is the wisdom tooth surgical removal. A well-established procedure, with known effects and pre-determined post-operative finds. Once this procedure generates pain, swelling and trismus. The metabolism of the NSAIDs are mainly originated on the family of cytochrome P450 (CYP) more accurately the CYP2C8 and CYP2C9 genes. In this context, the area from pharmacology, which studies the contribution of polymorphisms and genetic factors to the individual variability of responses to drug metabolism, called pharmacogenetics is growing and starting to show results regarding the clinical use of this drugs. In addition, the possible influence of genetic and tissue biomarkers at the descending inhibitory system of pain, may also impact the response and effects of NSAIDS, and this inhibitory system could be checked through the modulation of conditioned pain. In this aspect, the OPRM1 opioid receptor has been widely studied by pharmacogenetics, due to the structural variation, and its function in a variety of painful disorders. The ¼- opioid receptor (MOR), encoded by the OPRM1 gene naturally regulates the analgesic response to pain. Genetic variabilities in the OPRM1 gene, particularly A118G SNP have been associated with a number of functional purposes.Then, the aim of this study will be to assess the link between the different haplotypes of CYP2C8 and CYP2C9 genes and the clinical efficacy of ibuprofen after lower third molar extractions regarding pain, swelling and trismus, adverse reactions, the amount of pain medication used, the patient satisfaction with the drug and the influence of the ability on preoperative modulation of conditioned pain. We will evaluate also the relationship between the different haplotypes of OPRM1 gene (SNP A118G), the salivary concentrations of pro-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10 and TNF-±), and preoperative conditioned pain modulation.Therefore, 200 patients will be genotyped and phenotyped for these genes and their postoperative records with all data collected will be compared with the haplotypes found in the Brazilian population. For analysis of the proposed genes, saliva will be collected, which will serve as a source of genomic DNA. For molecular analysis it will be performed polymerase chain reaction (PCR). All tests will be conducted and validated by Applied Biosystems®.Also it will be held in the project BEPE, genetic sequencing of the genes CYP2C8, CYP2C9 and OPRM1, to verify possible correlations of these genes with postoperative pain and pain modulation. The stage will be held under the supervision of Professor Howard Jacob, who is Founder, President and Scientific Director of Envision Genomics, Inc. in Huntsville, Alabama, United States.