COX-2 Inhibitors in Dental Pain Management / Inhibidores de la COX-2 en el Tratamiento del Dolor Dental

ABSTRACT: Pain is a major symptom in many dental procedures. Studies show consistently that pain, including dental pain, is not effectively treated; management of pain is a critical and challenging component in dentistry. Improvement and efficacy on the treatment depends on knowing which treatments are the most effective. Knowing how well an analgesic works and its associated adverse effects is fundamental to clinical decision. The aim of this review is to provide information to the dentistry field on the treatment of dental pain specifically with COX-2 inhibitors providing a useful guide to dentist on controlling pain. Therefore, nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed analgesic agents in surgical outpatients. Major limitations of NSAIDs are their gastrointestinal (GI) adverse events (perforation, ulceration, and bleeding), impairment of hemostatic function, and renal failure (with long-term therapy). A new class of NSAIDs, COX2 selective inhibitors (Coxibs), have been developed with the aim of reducing the GI adverse events of traditional NSAIDs while maintaining their effective anti-inflammatory and analgesic properties.

RESUMEN: El dolor es un síntoma principal en muchos procedimientos dentales. Los estudios demuestran consistentemente que el dolor, incluido el dolor dental, no se trata de manera efectiva; el manejo del dolor es un componente crítico y desafiante en odontología. La mejora y la eficacia en el tratamiento depende de saber qué tratamientos son los más efectivos. Saber qué tan bien funciona un analgésico y sus efectos adversos asociados es fundamental para la decisión clínica. El objetivo de esta revisión es proporcionar información al campo de la odontología sobre el tratamiento del dolor dental específicamente con los inhibidores de la COX-2, proporcionando una guía útil para el control del dolor por parte del dentista. Por lo tanto, los fármacos antiinflamatorios no esteroideos (AINE) son los agentes analgésicos más comúnmente prescritos en pacientes ambulatorios quirúrgicos. Las principales limitaciones de los AINE son los eventos adversos gastrointestinales (perforación, ulceración y hemorragia), deterioro de la función hemostática e insuficiencia renal (con terapia a largo plazo). Una nueva clase de AINE, los inhibidores selectivos de la COX-2 (Coxibs), se han desarrollado con el objetivo de reducir los eventos adversos gastrointestinales de los AINE tradicionales mientras se mantienen sus propiedades antiinflamatorias y analgésicas efectivas.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

La combinación de atorvastatina y meloxicam inhibe la neuroinflamación y atenúa el daño celular en la isquemia cerebral experimental por embolia arterial / Atorvastatin-meloxicam association inhibits neuroinflammation and attenuates the cellular damage in cerebral ischemia by arterial embolism.

Introducción. El accidente cerebrovascular es la segunda causa de muerte y la primera de discapacidad en el mundo, y más de 85 % es de origen isquémico. Objetivo. Evaluar en un modelo de infarto cerebral por embolia arterial el efecto de la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, sobre la respuesta neuronal, los astrocitos y la microglia. Materiales y métodos. Se sometieron ratas Wistar a embolia de la arteria carótida y a tratamiento con meloxicam y atorvastatina, administrados por separado y conjuntamente, a las 6, 24, 48 y 72 horas. Se evaluó la reacción de las proteínas COX-2, GFAP y OX-42 en las neuronas, los astrocitos y la microglia mediante inmunohistoquímica y estudios morfológicos y de densitometría. Los datos obtenidos se evaluaron por medio de un análisis de varianza y de pruebas no paramétricas de comparación múltiple. Resultados. La isquemia cerebral por embolia arterial incrementó significativamente (p<0,001) la reacción de los astrocitos y la microglia, en tanto que la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, la redujeron. La isquemia produjo acortamiento de las proyecciones de los astrocitos, engrosamiento celular, ruptura de las expansiones protoplásmicas (clasmatodendrosis) y cambios morfológicos en la microglia propios de diversas etapas de actividad. En las zonas circundantes del foco se incrementó la reacción inmunológica de la COX-2 y se redujo en el foco isquémico, en tanto que el meloxicam y la atorvastatina redujeron significativamente (p<0,001) la reacción inmunológica en la zona circundante del foco, restableciendo la marcación de la ciclooxigenasa en el foco isquémico. Conclusión. La combinación de meloxicam y atorvastatina atenúa la respuesta de los astrocitos y la microglia en el proceso inflamatorio posterior a la isquemia cerebral por embolia arterial, reduciendo la degeneración neuronal y restableciendo el equilibrio morfológico y funcional del tejido nervioso.

Introduction: Stroke is the second leading cause of death and the first cause of disability in the world, with more than 85% of the cases having ischemic origin. Objective: To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association. Materials and methods: Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin at 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Data were evaluated by variance analysis and non-parametric multiple comparison. Results: Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p<0.001), whereas it was reduced by atorvastatin, meloxicam and their association. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various activity stages. In perifocal areas, immunoreactivity of COX-2 was increased and in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p<0.001) perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus. Conclusion: These results suggest that the meloxicam-atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring the morphological and functional balance of nervous tissue .

Treatment of Bartter syndrome. Unsolved issue, / Tratamento da síndrome de Bartter. Problema não resolvido,

Objective: To describe the results of a long-term follow-up of Bartter syndrome patients treated with different drugs. Method: Patients were diagnosed according to clinical and laboratory data. Treatment protocol was potassium supplementation, sodium, spironolactone, and non-steroidal anti-inflammatory drug. Patients who developed proteinuria were converted to angiotensin conversion enzyme inhibitor. The variables evaluated for each drug were Z-score for weight and stature, proteinuria, creatinine clearance, gastrointestinal complaints, amount of potassium supplementation, serum potassium and bicarbonate levels, and findings of upper digestive endoscopy. Results: 20 patients were included. Follow-up was 10.1 ± 5.2 years. 17 patients received indomethacin for 5.9 ± 5.3 years; 19 received celecoxib, median of 35 months; and five received enalapril, median of 23 months. During indomethacin, a statistically significant increase was observed in the Z-score for stature and weight, without a change in the creatinine clearance. Seven of 17 patients had gastrointestinal symptoms, and upper digestive endoscopy evidenced gastritis in three patients and gastric ulcer in four patients. During celecoxib use, a significant increase was detected in the Z-score for stature and weight and a reduction of hyperfiltration; seven patients presented gastrointestinal symptoms, and upper digestive endoscopy evidenced mild gastritis in three. During enalapril use, no significant changes were observed in the Z-score for stature, weight and creatinine clearance. The conversion to enalapril resulted in a significant reduction in proteinuria. Conclusion: The authors suggest starting the treatment with celecoxib, and replacing by ACEi if necessary, monitoring the renal function. The safety and efficacy of celecoxib need to be assessed in larger controlled studies. .

Objetivo: Descrever os resultados de um acompanhamento de longo prazo de pacientes com síndrome de Bartter tratados com diferentes medicamentos. Método: Pacientes diagnosticados segundo os dados clínicos e laboratoriais. Protocolo de tratamento: suplementação de potássio, sódio, espironolactona e medicamento anti-inflamatório não esteroidal. Os pacientes que desenvolveram proteinúria foram submetidos a inibidor da enzima de conversão da angiotensina. As variáveis avaliadas durante o uso de cada medicamento foram: escore Z para peso e estatura, proteinúria, depuração da creatinina, queixas gastrointestinais, quantidade da suplementação de potássio, níveis séricos de potássio e bicarbonato e achados da endoscopia digestiva alta. Resultados: Foram incluídos 20 pacientes. O acompanhamento foi de 10,1 ± 5,2 anos. No total, 17 pacientes receberam indometacina por 5,9 ± 5,3 anos, 19 receberam celecoxib por aproximadamente 35 meses e cinco receberam enalapril por aproximadamente 23 meses. Durante o uso de indometacina, observamos um aumento estatístico significativo no escore Z para estatura e peso, sem alteração na depuração da creatinina. 7/17 pacientes apresentaram sintomas gastrointestinais, e a endoscopia digestiva alta mostrou gastrite em três pacientes e úlcera gástrica em quatro. Durante o uso de celecoxib, detectamos um aumento significativo no escore Z para estatura e peso e uma redução da hiperfiltração; sete pacientes apresentaram sintomas gastrointestinais e a endoscopia digestiva alta mostrou gastrite leve em três pacientes. Durante o uso de enalapril, não observamos alterações significativas no escore Z para estatura, peso e depuração da creatinina. A mudança da medicação para enalapril resultou em uma ...

Nonsteroidal anti-inflammatory therapy: changes on renal function of healthy dogs

PURPOSE: To evaluate the renal function in healthy dogs submitted to nonselective and preferential COX-2 nonsteroidal anti-inflammatory drug (NSAID) therapy. METHODS: Twenty four healthy dogs were distributed into four groups (G) (n=6): ketoprofenG - treated with ketoprofen; nimesulideG - treated with nimesulid; meloxicanG - treated with meloxican; and etodolacG - treated with etodolaco. All the dogs received the NSAIDs for 10 days by oral route. Physical examination and renal function (urinalysis, urinary sodium and gamma-glutamyl transpeptidase (GGT), serum urea, creatinine, potassium and sodium, and endogenous creatinine clearance) were evaluated before, after five and ten days (T0, T5 and T10) of the treatment in all groups. RESULTS: Changes were observed in urinalysis, with a significant increase in renal cells in the urine at T5 and T10 in nimesulideG. Significant reduction in urinary sodium in nimesulideG at T5 was observed. The clearance values were lower in ketoprofenG at T10. CONCLUSIONS: Meloxicam and etodolac were the drugs that have proven to be safer for short-term therapy in healthy dogs in relation to renal function. NSAIDs ketoprofen and nimesulide should be used judiciously in dogs with renal dysfunction, since there are promoted changes in renal function.

Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors

Live attenuated vaccines have recently been introduced for preventing rotavirus disease in children. However, alternative strategies for prevention and treatment of rotavirus infection are needed mainly in developing countries where low vaccine coverage occurs. In the present work, N-acetylcysteine (NAC), ascorbic acid (AA), some nonsteroidal anti-inflammatory drugs (NSAIDs) and peroxisome proliferator-activated receptor gamma (PPARγ) agonists were tested for their ability to interfere with rotavirus ECwt infectivity as detected by the percentage of viral antigen-positive cells of small intestinal villi isolated from ECwt-infected ICR mice. Administration of 6 mg NAC/kg every 8 h for three days following the first diarrhoeal episode reduced viral infectivity by about 90%. Administration of AA, ibuprofen, diclofenac, pioglitazone or rosiglitazone decreased viral infectivity by about 55%, 90%, 35%, 32% and 25%, respectively. ECwt infection of mice increased expression of cyclooxygenase-2, ERp57, Hsc70, NF-κB, Hsp70, protein disulphide isomerase (PDI) and PPARγ in intestinal villus cells. NAC treatment of ECwt-infected mice reduced Hsc70 and PDI expression to levels similar to those observed in villi from uninfected control mice. The present results suggest that the drugs tested in the present work could be assayed in preventing or treating rotaviral diarrhoea in children and young animals.

Should we definitively abandon prophylaxis for patent ductus arteriosus in preterm new-borns?

Although the prophylactic administration of indomethacin in extremely low-birth weight infants reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage, it does not appear to provide any long-term benefit in terms of survival without neurosensory and cognitive outcomes. Considering the increased drug-induced reduction in renal, intestinal, and cerebral blood flow, the use of prophylaxis cannot be routinely recommended in preterm neonates. However, a better understanding of the genetic background of each infant may allow for individualized prophylaxis using NSAIDs and metabolomics.

Treatment Update on Portal Hypertension and Complications / 대한소화기학회지

Current understanding of the pathophysiology of portal hypertension has resulted in therapeutic approaches aimed at correcting the increased splanchnic blood flow and some of which have been already used in clinical practice. Recently new perspectives opened and erstwhile paradigm has been changed to focus on increased resistance to portal blood flow and the formation of portosystemic collateralization. Several studies revealed the clear-cut mechanisms of hepatic endothelial dysfunction and abnormal angiogenesis contributing to the development of portal hypertension. Thus the modulations of hyperdynamic circulation or angiogenesis seem to be valuable therapeutic targets. In the current review update, we discuss the multidisciplinary management of modulating hepatic vascular resistance and abnormal angiogenesis associated with portal hypertension. However, these new pharmacological approaches are still under investigation and widescale clinical application are needed to develop effective strategies.

Management of Eosinophilic Granuloma Occurring in the Appendicular Skeleton in Children

BACKGROUND: We compared indomethacin therapy with the more aggressive approaches of anti-cancer chemotherapy and surgery in the treatment of isolated Langerhans cell histiocytosis (LCH) of bone in children. METHODS: Comparisons were made with respect to healing of the lesion without recurrence, time to radiological healing of the lesion, time to functional recovery, and complications related to treatment. RESULTS: Complete radiologic healing of the lesion (mean, 15.3 months) and functional recovery (mean, 5.6 months) were observed in all patients treated with either approach. No significant differences were noted in the time to complete radiologic healing or the time to functional recovery between the two groups. There were no recurrences with either approach until the last follow-up (mean, 56 months). Complications were common with anti-cancer chemotherapy, but indomethacin was well-tolerated. CONCLUSIONS: Indomethacin seems to be effective for treating isolated LCH of bone in children. Hence, morbidities associated with aggressive treatment approaches such as anti-cancer chemotherapy or surgery can be avoided.

The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

We compared the clinical efficacy of orally administered valdecoxib and piroxicam for the prevention of pain, trismus and swelling after removal of horizontally and totally intrabony impacted lower third molars. Twenty-five patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Valdecoxib (40 mg) or piroxicam (20 mg) was administered in a double-blind, randomized and crossed manner for 4 days after the surgical procedures. Objective and subjective parameters were recorded for comparison of postoperative courses. Both agents were effective for postoperative pain relief (N = 19). There was a similar mouth opening at suture removal compared with the preoperative values (86.14 ± 4.36 and 93.12 ± 3.70 percent of the initial measure for valdecoxib and piroxicam, respectively; ANOVA). There was no significant difference regarding the total amount of rescue medication taken by the patients treated with valdecoxib or piroxicam (173.08 ± 91.21 and 461.54 ± 199.85 mg, respectively; Wilcoxon test). There were no significant differences concerning the swelling observed on the second postoperative day compared to baseline measures (6.15 ± 1.84 and 8.46 ± 2.04 mm for valdecoxib and piroxicam, respectively; ANOVA) or on the seventh postoperative day (1.69 ± 1.61 and 2.23 ± 2.09 mm for valdecoxib and piroxicam, respectively; ANOVA). The cyclooxygenase-2 selective inhibitor valdecoxib is as effective as the non-selective cyclooxygenase inhibitor piroxicam for pain, trismus and swelling control after removal of horizontally and totally intrabony impacted lower third molars.

A study on the effects of diclofenac sodium and etoricoxib in the treatment of osteoarthritis.

Diclofenac sodium, a non-selective cyclo-oxygenase inhibitor and etoricoxib, a selective cyclo-oxygenase-2 inhibitor have been widely used in treatment of patients with osteo-arthritis. Five hundred and eighty-five patients with uncomplicated knee osteo-arthritis were randomly allocated into 3 equal groups and received either diclofenac sodium, etoricoxib or placebo in a double-blind manner. The response in both the drug groups was comparable and much more than placebo group. The study shows that etoricoxib provides better clinical efficacy and gastro-intestinal tolerability in osteo-arthritis in comparison to diclofenac sodium presumably due to the selective inhibition of cyclo-oxygenase-2 by etoricoxib.

Comparison of etoricoxib and indomethacin for the treatment of experimental periodontitis in rats

We investigated the effect of etoricoxib, a selective cyclooxygenase-2 inhibitor, and indomethacin, a non-selective cyclooxygenase inhibitor, on experimental periodontitis, and compared their gastrointestinal side effects. A ligature was placed around the second upper left molars of female Wistar rats (160 to 200 g). Animals (6 per group) were treated daily with oral doses of 3 or 9 mg/kg etoricoxib, 5 mg/kg indomethacin, or 0.2 mL saline, starting 5 days after the induction of periodontitis, when bone resorption was detected, until the sacrifice on the 11th day. The weight and survival rate were monitored. Alveolar bone loss (ABL) was measured as the sum of distances between the cusp tips and the alveolar bone. The gastric mucosa was examined macroscopically and the periodontium and gastric and intestinal mucosa were examined by histopathology. The ongoing ABL was significantly inhibited (P < 0.05) by 3 and 9 mg/kg etoricoxib and by indomethacin: control = 4.08 ± 0.47 mm; etoricoxib (3 mg/kg) = 1.89 ± 0.26 mm; etoricoxib (9 mg/kg) = 1.02 ± 0.14 mm; indomethacin = 0.64 ± 0.15 mm. Histopathology of periodontium showed that etoricoxib and indomethacin reduced inflammatory cell infiltration, ABL, and cementum and collagen fiber destruction. Macroscopic and histopathological analysis of gastric and intestinal mucosa demonstrated that etoricoxib induces less damage than indomethacin. Animals that received indomethacin presented weight loss starting on the 7th day, and higher mortality rate (58.3 percent) compared to etoricoxib (0 percent). Treatment with etoricoxib, even starting when ABL is detected, reduces inflammation and cementum and bone resorption, with fewer gastrointestinal side effects.

Prevention of Hepatocelluar Carcinoma / 대한소화기학회지

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has the third highest mortality rate among malignancies in South Korea. Despite the continuing efforts for the early detection of HCC, the mortality rate and prognosis have not been improved yet. Its clinical behavior is quite different from other cancers. High recurrence rate after curative treatment might be the reason for poor prognosis. Several methods including chemoprevention, blocking the development of HCC, have been under investigations. The vaccine for hepatitis, in the form of primary prevention, is considered to be the most effective one inhibiting the development of liver disease. Furthermore, keeping away from hepatotoxic agents is another way for preventing liver cell injuries. Secondary prevention is to stop the developement of HCC in chronic liver diseases. Since the level of DNA in hepatitis B virus (HBV) hepatitis patients is closely related with the development of HCC, it is helpful to lower the DNA level using anti-viral agents. In addition, IFN, one of the anti-viral agents, can inhibit HCV hepatitis from tumorigenesis. Cyclo-oxygenase (COX)-2 inhibitors are also alleged to have a function in interrupting the development of HCC. Tertiary prevention means the prevention of recurrence of HCC after successful treatment. Because of high recurrence rate, the prevention of recurrence should be one of the important factors affecting the prognosis of HCC. Up to now, COX inhibitors, retinoic acids, vitamin K2, glycyrrhizin epigallocatechin-3-gallate (EGCG), and ginseng had been reported to be effective for the chemoprevention of HCC. Further studies are required for an advancement in the prevention of HCC.

Oral ibuprofen prophylaxis for symptomatic patent ductus arteriosus of prematurity.

BACKGROUND: The oral suspension form of ibuprofen has been shown to have the same efficacy and safety as indomethacin in the treatment of symptomatic PDA, however its role is still questionable in the prophylaxis of symptomatic PDA. OBJECTIVES: 1. To assess the efficacy and safety of the drug in the prevention of symptomatic PDA in premature infants. 2. To study its pharmacokinetics-pharmacodynamics relationship. MATERIAL AND METHOD: A randomized, single-blinded, controlled study was performed on premature neonates with a gestational age between 28-32 weeks, birthweight < or = 1500 grams at the neonatal unit, Queen Sirikit National Institute of Child Health from July 2003 to April 2004. Three doses of ibuprofen suspension or placebo were given 24 hours apart. Clinical evaluation was performed daily until the 28th day of life. Echocardiogram was performed prior to the drug administration, on the 3rd and 7th day of life. RESULTS: There were 22 and 20 cases in the ibuprofen and control group respectively. The epidemiologic data between the groups before enrollment showed no significant differences. Prevalence of symptomatic PDA was lower in the ibuprofen than in the control group without any significant side effects (0/22 vs 5/20, p = 0.015 on day 3 and 0/22 vs 6/20, p = 0.006 on day 7). Comparing with the pharmacokinetic study in older children and adult, the present study revealed nearly the same Cmax but longer Tmax and T1/2 in premature neonates. CONCLUSION: Oral ibuprofen suspension could reduce the prevalence of symptomatic PDA without any significant side effects.

Salt wasting disorder in the newborn.

The clinical presentation of pseudohypoaldosteronism (PHA) mimics congenital adrenal hyperplasia (CAH). Poor response of the dehydration and electrolyte abnormalities to steroid therapy should make one suspect PHA. The treatment is supportive in the form of salt replacement and sodium resonium. We report a case of PHA that presented as salt wasting on the second day of life, initially appearing like CAH. The baby responded well to sodium resonium and salt replacement.

Comparative efficacy of aceclofenac and etoricoxib in post extraction pain control: randomized control trial.

The study is a prospective randomized double blind clinical trial comparing the efficacy of nonselective NSAIDs (Aceclofenac) and highly selective COX-2 inhibitors (Etoricoxib) in post extraction pain control. The primary efficacy was judged by overall assessment of onset and duration of analgesic effect and rate of decrease in pain intensity by a visual analogue scale over a 3-day investigation period. 100 patients were enrolled in the study (50 patients in aceclofenac group and 50 patients in etoricoxib group). Twice-daily dosage of aceclofenac 100 mg and etoricoxib 60 mg were recommended for the double blind study. 64 patients completed the study. Efficacy of pain control over baseline data documented in both the treatment groups were statistically significant (p<0.05). There was no significant difference between the two drugs.

Role of cyclooxygenase-2 in lipopolysaccharide-induced hyperalgesia in formalin test.

Lipopolysaccharide (LPS)-induced hyperalgesia and the role of cyclooxygenase (COX) isoforms in acute and chronic nociceptive assays have been well established. However, the role of COX isoforms in LPS-induced hyperalgesia in the formalin test is not clear. Thus, the present study was undertaken to characterize the time course of formalin-induced nociceptive response in LPS-pretreated mice and to investigate possible effects of COX inhibitors to address the potential role of COX isoforms in LPS-induced hyperalgesia in the formalin test. All the animals showed typical biphasic response to formalin challenge. At 0 hr (immediately) and 4 hr after LPS pretreatment, animals did not show any alteration in formalin-induced tonic pain. However, 12 and 16 hr after LPS pretreatment, there was a significant increase in the late phase of formalin-induced nocifensive response as compared to control mice. Treatment with intravenously administered ketorolac (a nonselective COX inhibitor) significantly and dose-dependently inhibited the late phase of formalin-induced nociceptive behaviour in saline and LPS-pretreated mice. In contrast, parecoxib (prodrug of valdecoxib, a selective COX-2 inhibitor) or dexamethasone (COX-2 transcription inhibitor), when administered intravenously or intraperitoneally, respectively, did not show antinociceptive effect in the formalin test in saline-pretreated mice. However, both the agents significantly and dose-dependently decreased the late phase nociceptive behaviour of the formalin test in LPS-pretreated mice to the level of the animals that received saline pretreatment. These results suggest that induction of COX-2 by proinflammatory mediators and subsequent release of prostaglandins could be responsible for LPS enhancement of formalin-induced nocifensive behaviour and supports an important role of COX-2 in LPS-induced hyperalgesia in the formalin test.

The expression of COX-1 and COX-2 following brain injuries / 法医学杂志

Cyclooxygenase (COX) is the obligate, rate-limiting enzyme for the conversion of arachidonic acid into prostaglandins, which mediate mitogenesis, apoptosis, angiogenesis, blood flow, secondary injury, and inflammation. COX is consist of 2 subtypes: COX-1 and COX-2. In recent years, there are a number of lines of evidence that COX-1 and COX-2 play a important in role brain injuries.

Role of parecoxib in pre-emptive analgesia: comparison of the efficacy and safety of pre- and postoperative parecoxib in patients undergoing general surgery.

Management of acute postoperative pain remains sub-optimal despite the availability of multiple analgesics and improved pain management strategies (with nearly 80 % of patients reporting moderate to extreme pain following surgery). To evaluate the role of parecoxib as a pre-emptive analgesic in patients undergoing general surgery, the present study was undertaken. Eighty patients of either sex, aged 18 to 70 years, requiring elective ambulatory general surgery like hernioplasty, appendicectomy, cholecystectomy, etc, were enrolled in this prospective, randomised, assessor-blind, parallel-group, comparative trial. Eligible patients were randomised to receive a single dose of 40 mg of parecoxib IM/IV either 30-45 minutes prior to induction of anesthesia (pre-emptive analgesia) or in the postoperative period when one reported pain or when the effects of anesthesia were worn off (whichever was earlier). The primary measures of efficacy were pain intensity scores measured on a visual analog scale (VAS) and pain relief before and after therapy. Adverse event monitoring, physical examination and changes in laboratory tests, chest x-ray and ECG were used to evaluate safety. A comparison of the pain intensity scores between the two groups revealed that patients treated with parecoxib preoperatively did not complain of pain in the entire postoperative period up to 12 hours. Mild pain (1.05+/-1.36) was reported by patients in this group only at the 24 hours assessment. On the other hand, patients treated with parecoxib in the postoperative period, experienced severe pain at baseline, which declined gradually up to 12 hours. The difference in the pain intensity scores between the two groups was statistically significant at all the time intervals from 0 hour to 24 hours. All the 40 patients (100%) in the pre-operatively treated group reported total pain relief at 12 hours compared to only 22 patients (55%) in the postoperative period. At 24 hours total pain relief was reported by 70% of the patients in the pre-operatively treated group, compared to only 20% (8) patients in the postoperatively treated group. The difference between the two groups was statistically significant in favour of the pre-operatively treated group (p<0.05). Present results suggested that pre-operative administration of parecoxib was more effective than a postoperative use in providing pain relief in postoperative period in patients undergoing elective general surgical procedures. Both the regimens were well tolerated. Based on the above data, it appears that pre-operative dose of parecoxib 40 mg IV/IM is a useful optionfor pre-emptive analgesia in general surgical practice.