In clinical situations, most of the patients suffer from inflammation and acute postoperative pain after surgery. Postoperative pain has been emphasized as a very crucial issue in improving the quality of medical care in each medical center. Therefore, management of the postoperative pain is an effective approach to reduce the painful unpleasant feeling, complications, and death rate after surgery. Surgical trauma results in the induction of COX-2, leading to the release of prostaglandins, which sensitize peripheral nociceptors and increase the excitability of spinal neurons, producing pain hypersensitivity in the surrounding uninjured tissue.The purpose of this study is to test the preventive effect of COX-2 inhibitor SC-236 for post-operative pain by rat plantar incision model.Then, we explored whether SC-236 is more effective in reducing the hyperalgesia and inflammation response administered before incision than after incision. Furthermore, we used male Sprague-Dawley rats received plantar incision were used in this study, the rats received subcutaneous injection of SC-236 before or after plantar incision. Behavior teste of mechanical allodynia¡Bthermal hyperalgesia and COX-2 expression level was determined at 4 h and 1, 2, and 3 days after surgery. Mechanical allodynia was measured by mechanical withdrawal threshold that was determined by stimulating with von Frey filaments stimulation. Thermal hyperalgesia was measured by thermal withdrawal thermal tested by radioactive thermal assay. Mechanical allodynia¡Bthermal hyperalgesia and COX-2 expression level were measured at various time points by behavior teste¡Breal-time polymerase chain reaction¡Bwestern blot and immunohistochemistry. The data from pre-incisional injection of SC-236 was compared with that from post-incisional injection of SC-236.The results revealed pre-incisional injection of COX-2 inhibitor significantly inhibited thermal hyperalgesia but not mechanical allodynia then post-incisional injection of COX-2 inhibitor group. Skin of pre-incisional injection of SC-236 show significant decreased mRNA expression of COX-2 at 1 day and 2 day after incision evidenced by real-time polymerase chain reaction. Western blot and immunohistochemistry also show significant decreased protein expression of COX-2 at 4 hours and 1 day after incision. Therefore, pre-incisional administration of SC-236 could prevent the surgical wound induced thermal hyperalgesia and decrease mRNA and protein expression level of cutaneous COX-2 at 4 hours and one day after surgical incision compared to post-incisional administration of SC-236 .

Background: Thousands of Canadians undergo cardiac surgery each year with the aim of relieving symptoms (e.g., angina) and improving health-related-quality-of-life (HRQoL). Despite the demonstrated symptom-related benefits of these surgeries, evidence suggests that the development of chronic post-surgical pain (CPSP) is a major clinical problem. To date, several perioperative factors have been examined for their potential to confer risk for CPSP. Purpose: The purpose of the study was to explore the association between preoperative moderate to severe anxiety and depressive symptoms; moderate to severe acute postoperative pain; and cumulative opioid dose consumption with the development of CPSP at six months and 12 months after cardiac surgery. Method: Design. This thesis was a prospective observational cohort sub-study of adults undergoing cardiac surgery in a tertiary care hospital setting (n=735), recruited from Hamilton Health Sciences, Canada over a five year period. Measures. The independent variables included state anxiety, depressive symptoms, acute postoperative pain intensity, and opioid dose consumption. At baseline, the Spielberger State-Trait Anxiety Inventory (STAI) assessed state anxiety and the Hospital Anxiety and Depression Scale (HADS) assessed depressive symptoms. The Brief Pain Inventory-Short Form (BPI-SF) assessed acute postoperative pain intensity on postoperative days three (in-hospital) and 30 (at home via telephone). All instruments have established reliability and validity in cardiac surgery patients (e.g., STAI Cronbach’s alpha (α) =0.82; HADS α=0.81; BPI-SF α=0.87). Medical records were reviewed and total dose of opioids consumed up to three days postoperatively, were collected via analgesic chart audit and converted into milligrams of parenteral morphine equivalent dose using standard dosage tables. Dependent variable. The primary outcome of CPSP was assessed dichotomously (i.e., yes/no) at six months and 12 months after cardiac surgery. If present, CPSP was assessed via the BPI-SF. At baseline, data was collected on pre-specified model covariates (e.g., age, sex). Data Analyses. Logistic regression was used to model the primary outcome with the presence of CPSP at six months and 12 months, while adjusting for model covariates. Secondary linear regression models were constructed to examine the effect of the independent variables on the severity of CPSP with statistical significance set at p-values <0.05. Results: The incidence of CPSP was 8.7% at six months and 4.1% at 12 months after cardiac surgery. Baseline demographics (i.e., age, sex) and medical status (i.e., diabetes mellitus) were significantly associated with the presence of CPSP. Moderate to severe preoperative anxiety was not significantly associated with CPSP at six months (adjusted OR 0.629, 95% CI [0.300, 1.322], p=0.222) or 12 months (adjusted OR 0.743, 95% CI [0.242, 2.285], p=0.604). Moderate to severe preoperative depressive symptom was not significantly associated with CPSP at six months (adjusted OR 0.676, 95% CI [0.152, 3.005], p=0.607) or 12 months (adjusted OR 3.216, 95% CI [0.835, 12.382], p=0.089). Acute postoperative pain rated as pain ‘right now’ on day three was significantly associated with CPSP at six months (adjusted OR 2.263, 95% CI [1.255, 4.081], p=0.007) and 12 months (adjusted OR 2.749, 95% CI [1.174, 6.441], p=0.020). Acute postoperative pain ‘right now’ on day 30 was significantly associated with CPSP at six months (adjusted OR 2.913, 95% CI [1.304, 6.505], p=0.009). Cumulative opioid dose consumed was significantly associated with the development of CPSP at six months (adjusted OR 1.001, 95% CI [1.000, 1.002], p=0.003) and 12 months (adjusted OR 1.001, 95% CI [1.000, 1.001], p=0.033) after cardiac surgery. Significance: The findings demonstrate that acute postoperative pain ‘right now’ and cumulative opioid dose consumed are risk factors for CPSP after cardiac surgery. These findings offer targets for nursing staff to identify potentially at-risk patients, implement evidence-based pain management strategies, as well as contribute to nursing-led research designed to target CPSP after cardiac surgery. / Dissertation / Doctor of Philosophy (PhD)

Submitted by MARCELO DE JESUS MARTINS null (celoufba@yahoo.com.br) on 2018-01-05T11:45:24Z No. of bitstreams: 1 Marcelo Martins (Tese de Doutorado).pdf: 3508982 bytes, checksum: ff73bd80060bf710ecc113d389df649e (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-01-05T17:19:45Z (GMT) No. of bitstreams: 1 martins_mj_dr_bot.pdf: 3508982 bytes, checksum: ff73bd80060bf710ecc113d389df649e (MD5) / Made available in DSpace on 2018-01-05T17:19:45Z (GMT). No. of bitstreams: 1 martins_mj_dr_bot.pdf: 3508982 bytes, checksum: ff73bd80060bf710ecc113d389df649e (MD5) Previous issue date: 2017-12-11 / Justificativa: a obesidade é uma doença crônica caracterizada por acúmulo excessivo de gordura corporal. Devido aos riscos associados, é considerada um grande problema de saúde pública nos países desenvolvidos. A cirurgia bariátrica (gastroplastia aberta) tem sido usada como uma estratégia importante para tratar esta condição nos países em desenvolvimento, especialmente quando associada a outras comorbidades. A qualidade de recuperação, no entanto, tem sido uma preocupação frequente no manejo pós-operatório desses pacientes. A pregabalina é um análogo estrutural do neurotransmissor ácido gama-aminobutírico (GABA) que se liga à subunidade alfa-2 do canal de cálcio voltagem dependente, bloqueando o desenvolvimento da hiperalgesia e a sensibilização central à dor. Objetivo: o objetivo principal da pesquisa foi avaliar o efeito da pregabalina perioperatória versus placebo na qualidade de recuperação pós-operatória em pacientes submetidos à cirurgia bariátrica. Métodos: trata-se de estudo prospectivo, randomizado, controlado com placebo, duplo cego. Após a aprovação do Comitê de Ética, setenta pacientes submetidos à gastroplastia abdominal foram randomizados para receber pregabalina, grupo 1 (75 mg por via oral 1 hora antes da cirurgia) ou uma pílula de placebo idêntica, grupo 2. O desfecho primário foi a avaliação da qualidade da recuperação (questionário QoR-40) em 24 horas. Os resultados secundários incluíram o consumo de opioides e os escores de dor pós-operatória. Um valor de P <0,05 foi usado para rejeitar erro de tipo I. Resultados: foram randomizados setenta pacientes e 60 indivíduos completaram o estudo. A mediana dos escores globais de recuperação (qualidade de recuperação QoR-40) às 24 horas após a cirurgia no grupo de pregabalina foi de 185 (176-191) x 184 (174-192) no grupo placebo (P = 0,95). O consumo total de opioides nas 24 horas não apresentou diferença estatisticamente significativa entre os grupos. Além disso, a incidência de náusea, o vômitos e o tempo de alta da unidade de cuidados pós-anestésicos não foram significativamente reduzidos no grupo pregabalina em comparação com o placebo. Conclusões: o uso pré-operatório de pregabalina não resulta em melhora na qualidade da recuperação pós-operatória, redução dos escores de dor, bem como redução do consumo de opioides em pacientes submetidos à cirurgia bariátrica. / Background: obesity is a chronic disease characterized by excessive accumulation of body fat. Due to the associated risks, it has been considered a major public health problem in developed countries. Bariatric surgery (open gastroplasty) has been used as an important strategy to treat this condition in developing countries, especially when associated with other comorbidities. The quality of recovery, however, has been a frequent concern in the postoperative management of these patients. Pregabalin is a structural analogue of the gamma-aminobutyric acid neurotransmitter (GABA) that binds to the alpha-2-subunit of the voltage-dependent calcium channel, blocking the development of hyperalgesia and central pain sensitization. Objective: the main objective of the current investigation was to evaluate the effect of perioperative pregabalin versus placebo on postoperative quality of recovery in patients undergoing bariatric surgery. Methods: the study was a prospective, randomized, placebo-controlled, double-blinded trial. After ethics committee approval, seventy patients undergoing abdominal gastroplasty were randomized to receive pregabalin, group 1 (75 mg orally 1 hour before surgery) or an identical placebo pill, group 2. The primary outcome was the quality of recovery-40 score at 24 hours. Secondary outcomes included opioid consumption and postoperative pain scores. A P value <0.05 was used to reject type I error. Results: seventy patients were randomized and 60 subjects completed the study. The median in global recovery scores (quality of recovery-40) at 24 hours after surgery in pregabalin group was 185 (176-191) x 184 (174-192) in placebo group (P = 0.95). Total opioid consumption in the 24 hours did not present a statistically significant difference between the groups. In addition, nausea, vomiting, and time to post-anesthesia care unit discharge were not significantly reduced in the pregabalin group compared with placebo. Conclusions: preoperative use of pregabalin showed no improve in quality of postoperative recovery, no better pain relief as well as reduction of opioid consumption in patients submitted to bariatric surgery.

Orientador: Norma Sueli Pinheiro Módolo / Resumo: Justificativa: a obesidade é uma doença crônica caracterizada por acúmulo excessivo de gordura corporal. Devido aos riscos associados, é considerada um grande problema de saúde pública nos países desenvolvidos. A cirurgia bariátrica (gastroplastia aberta) tem sido usada como uma estratégia importante para tratar esta condição nos países em desenvolvimento, especialmente quando associada a outras comorbidades. A qualidade de recuperação, no entanto, tem sido uma preocupação frequente no manejo pós-operatório desses pacientes. A pregabalina é um análogo estrutural do neurotransmissor ácido gama-aminobutírico (GABA) que se liga à subunidade alfa-2 do canal de cálcio voltagem dependente, bloqueando o desenvolvimento da hiperalgesia e a sensibilização central à dor. Objetivo: o objetivo principal da pesquisa foi avaliar o efeito da pregabalina perioperatória versus placebo na qualidade de recuperação pós-operatória em pacientes submetidos à cirurgia bariátrica. Métodos: trata-se de estudo prospectivo, randomizado, controlado com placebo, duplo cego. Após a aprovação do Comitê de Ética, setenta pacientes submetidos à gastroplastia abdominal foram randomizados para receber pregabalina, grupo 1 (75 mg por via oral 1 hora antes da cirurgia) ou uma pílula de placebo idêntica, grupo 2. O desfecho primário foi a avaliação da qualidade da recuperação (questionário QoR-40) em 24 horas. Os resultados secundários incluíram o consumo de opioides e os escores de dor pós-operatória. Um valor de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: obesity is a chronic disease characterized by excessive accumulation of body fat. Due to the associated risks, it has been considered a major public health problem in developed countries. Bariatric surgery (open gastroplasty) has been used as an important strategy to treat this condition in developing countries, especially when associated with other comorbidities. The quality of recovery, however, has been a frequent concern in the postoperative management of these patients. Pregabalin is a structural analogue of the gamma-aminobutyric acid neurotransmitter (GABA) that binds to the alpha-2-subunit of the voltage-dependent calcium channel, blocking the development of hyperalgesia and central pain sensitization. Objective: the main objective of the current investigation was to evaluate the effect of perioperative pregabalin versus placebo on postoperative quality of recovery in patients undergoing bariatric surgery. Methods: the study was a prospective, randomized, placebo-controlled, double-blinded trial. After ethics committee approval, seventy patients undergoing abdominal gastroplasty were randomized to receive pregabalin, group 1 (75 mg orally 1 hour before surgery) or an identical placebo pill, group 2. The primary outcome was the quality of recovery-40 score at 24 hours. Secondary outcomes included opioid consumption and postoperative pain scores. A P value <0.05 was used to reject type I error. Results: seventy patients were randomized and 60 subjects comple... (Complete abstract click electronic access below) / Doutor

MUDr. Olga Matoušková - the dissertation theses The influence of individual genetic predisposition to the pharmacokinetics and pharmacodynamics of chosen opioids ABSTRACT Introduction: The aim of this thesis is to study the influence of polymorphism of CYP2D6 and MDR1 on the pharmacokinetics and pharmacodynamics of tramadol in healthy volunteers using measurement. A secondary objective is to evaluate these polymorphisms in relation to the analgesic efficacy and side effects of piritramide for acute postoperative pain. Materials and methods: In two prospective work studying the influence of genetic predisposition on the pharmacokinetic and pharmacodynamic parameters of tramadol, we included a total of 90 healthy volunteers. Clinical studies on opioid analgesia and influence of genetic predisposition to the pharmaco-therapeutic effects and side effects in patients with acute postoperative pain, we included a total of 161 patients with acute postoperative pain. Polymorphism genotyping CYP2D6 and MDR1 gene we performed PCR - RFLP analysis, to determine concentrations of tramadol and metabolite, we used gas and liquid chromatography and pharmacodynamic effects of opioids was evaluated by pupilometric measurement and visual analogue scale. Results and conclusion: Variability of the opioid effect is influenced by...

MUDr. Olga Matoušková - the dissertation theses The influence of individual genetic predisposition to the pharmacokinetics and pharmacodynamics of chosen opioids ABSTRACT Introduction: The aim of this thesis is to study the influence of polymorphism of CYP2D6 and MDR1 on the pharmacokinetics and pharmacodynamics of tramadol in healthy volunteers using measurement. A secondary objective is to evaluate these polymorphisms in relation to the analgesic efficacy and side effects of piritramide for acute postoperative pain. Materials and methods: In two prospective work studying the influence of genetic predisposition on the pharmacokinetic and pharmacodynamic parameters of tramadol, we included a total of 90 healthy volunteers. Clinical studies on opioid analgesia and influence of genetic predisposition to the pharmaco-therapeutic effects and side effects in patients with acute postoperative pain, we included a total of 161 patients with acute postoperative pain. Polymorphism genotyping CYP2D6 and MDR1 gene we performed PCR - RFLP analysis, to determine concentrations of tramadol and metabolite, we used gas and liquid chromatography and pharmacodynamic effects of opioids was evaluated by pupilometric measurement and visual analogue scale. Results and conclusion: Variability of the opioid effect is influenced by...