Blockade of glucocorticoid receptors prevents the increase in urea synthesis after hysterectomy in rats

The postoperative increase in hepatic conversion of amino nitrogen to urea nitrogen seems to be a primary cause of post-surgical catabolism. The importance of glucocorticosteroids for the spontaneous urea nitrogen synthesis rate (UNSR) and for the maximally amino acid-stimulated capacity of urea nitrogen synthesis (CUNS) was investigated 3 and 24 h postoperatively, respectively, in hysterectomized rats. Corticosteroid effects were neutralized by glucocorticoid receptor blockade by the pharmacological analogue RU486. Hysterectomy doubled UNSR from 3.16 +/- 0.20 to 6.12 +/- 0.27 mumol (per min per 100 g body weight) after 3 h (P less than 0.01) and increased CUNS by 40% from 7.47 +/- 0.30 to 10.29 +/- 0.41 mumol (per min per 100 g body weight) after 24 h (P less than 0.01). These changes were both normalized by the receptor blockade. Hysterectomy decreased total blood alpha-amino nitrogen concentration by 25% from 3.4 +/- 0.2 to 2.6 +/- 0.2 mmol l-1 (P less than 0.05) 3 h after surgery, which was normalized by glucocorticoid receptor blockade. Hysterectomized rats lost 10 +/- 1 g the first 24 h after surgery. The blockade reduced the weight loss to 6 +/- 1 g body weight (P less than 0.05) without changing food intake. The results indicate that glucocorticoid action plays a major role in the postoperative increase in hepatic amino nitrogen conversion.     

Effect of glucagon immunoneutralization on the increase in urea synthesis after hysterectomy in rats

Abstract. To study the effect of glucagon immunoneutralization on postoperative changes of urea synthesis, hysterectomized rats were given one injection of a specific high titre antibody against pancreatic glucagon 24 h before operation raising the plasma glucagon binding capacity to values 10–20 times higher than the plasma glucagon concentration in control animals. Earlier studies have shown that the spontaneous rate of urea-N synthesis (UNSR) doubles 3 h after operation, and that the Vmax of the process, the capacity of urea-N synthesis (CUNS) is 50% higher than normal values 24 h after operation. Therefore, the effect of glucagon on UNSR and CUNS were investigated 3 and 24 h postoperatively, respectively. Control animals were given non immune rabbit serum. Glucagon immunoneutralization partly normalized the early increase in UNSR 3 h postoperatively (control: 4.7 ± 0.3, hysterectomy + serum: 6.7 ± 0.4, hysterectomy + Gluc-Ab: 5.5 ± 0.4 μmol (min.100 g BW)^-1), but had no effect on the increase of CUNS 24 h postoperatively (control: 7.9 ± 0.3, hysterectomy + serum: 9.5 ± 0.3, hysterectomy + Gluc - Ab: 9.8 ± 0.5 μmol (min-100 g BW)^-1).
This shows that glucagon is important for the early postoperative increase in the efficacy of urea synthesis, whereas the late increase in capacity seems not to depend on hyperglucagonemia.     

Methylprednisolone prevents the development of autotomy and neuropathic edema in rats, but has no effect on nociceptive thresholds

Corticosteroids are probably an effective treatment for some types of neuropathic pain and complex regional pain syndromes. This study examined the effects of systemic methylprednisolone (MP) on acute nociception and on pain behavior and hyperalgesia in normal and neuropathic rats. There was no dose-response to intraperitoneal MP (up to 12 mg/kg) for nociceptive thresholds to heat (Peltier) or mechanical (analgesy-meter and von Frey fibers) stimuli in normal rats. Chronic high dose MP (3 mg/kg per day for 21 days) also had no effect on acute nociceptive thresholds in normal rats. After sciatic nerve section in rats a saphenous nerve mediated hyperalgesia to heat and mechanical stimuli gradually developed over 21 days. High dose MP (3 mg/kg per day for 21 days) had no effect on this adjacent neuropathic hyperalgesia. When systemic MP was started immediately after bilateral sciatic and saphenous nerve transection there was a dose-dependent reduction in autotomy behavior. Substance P has been proposed as a mediator of neuropathic pain and edema. Single dose MP (12 mg/kg) slightly reduced the substance P mediated extravasation induced with electrical stimulation of the saphenous nerve. Chronic MP (3.4 mg/kg per day for 28 days) severely reduced the neurogenic extravasation induced with saphenous nerve stimulation. Sciatic sectioned rats developed hindpaw edema between 7 and 14 days after surgery, and this neuropathic edema did not develop in rats chronically treated with MP (3.4 mg/kg per day). These results demonstrate that corticosteroids did not affect nociceptive thresholds in normal or neuropathic hyperalgesic rats. Chronic steroid treatment did prevent the development of autotomy and neuropathic edema, and completely blocked neurogenic extravasation, findings consistent with the hypothesis that primary afferent substance P release mediates autotomy pain behavior and neuropathic edema. This may be a relevant model for examining the effects of corticosteroids on neuropathic pain and complex regional pain syndromes.     

鸢尾素对新生大鼠高胆红素血症抗炎作用的研究

摘要目的：探讨鸢尾素干预高胆红素血症新生大鼠脑组织炎症反应的影响。方法：将66只新生SD（Sprague-Dawley）大鼠,采用抽签法随机分为正常对照组（A组）和模型组（M组）,于7日龄、10日龄采用腹腔注射胆红素溶液的方法建立高胆红素血症模型。末次注射后,从A组、M组中随机选取6只大鼠,用于验证模型建立成功,然后将M组随机分为B组与C组,C组大鼠侧脑室注射80μg/kg剂量鸢尾素溶液,余各组注射等量磷酸盐缓冲液。侧脑室注射后,根据不同处死点,将A、B、C各组进一步分为3个亚组,在各时间点进行神经行为学检测,苏木精-伊红染色（hematoxylin-eosin staining, HE）检测皮质或海马神经细胞形态,酶联免疫吸附测定（enzyme-linked immunosorbent assay, ELISA）检测肿瘤坏死因子（tumor necrosis factor-alpha, TNF-α）、白细胞介素1β（interleukin-1 beta, IL-1β）、白细胞介素-6 （interleukin, IL-6） 的浓度。结果：平面翻正反射：12h时,3组大鼠所需时间无显著性差异（P>0.05）;24h时,B、C组大鼠长于A组大鼠（P<0.05）;48h时,B组大鼠长于A、C组大鼠（P<0.05）,A、C2组大鼠无显著性差异（P>0.05）。各时间点3组大鼠方向趋向性试验均无显著性差异（P>0.05）。HE：A组大鼠皮质神经元结构清晰完整,但海马神经元数量出现减少;B、C组大鼠皮质、海马等区域神经元数目减少,结构紊乱,可见不同程度病理损害,C组优于B组。Elisa：B组脑组织各时间点TNF-α、IL-1β、IL-6的浓度均高于A组（P<0.05）;C组脑组织各时间点TNF-α、IL1β、IL-6的浓度均低于B组,差异具有显著性意义（P<0.05）;C组大鼠脑组织TNF-α浓度在12h时高于A组大鼠（P<0.05）,在24h、48h低于A组大鼠（P<0.05）;C组大鼠脑组织IL-6的浓度在12h、24h均低于A组大鼠（P<0.05）,48h时,C组大鼠脑组织IL-6的浓度与A组大鼠无显著性差异（P>0.05）;C组大鼠脑组织IL-β的浓度在3个时间点均与A组大鼠无显著性差异（P>0.05）。结论：鸢尾素可有效减少高胆红素血症新生大鼠脑组织TNF-α、IL-1β、IL-6的释放,发挥抗炎作用。     

一氧化氮对急性肺损伤大鼠白细胞介素-6、环氧合酶-2的影响

目的探讨吸入一氧化氮(NO)对急性肺损伤大鼠肺组织白细胞介素-6(IL-6)和环氧合酶-2(COX-2)的影响。方法脂多糖(LPS)气管内滴注,制造大鼠急性肺损伤模型,吸入NO,检测肺组织中IL-6和COX-2的表达。结果LPS气管内滴注后,肺组织中COX-2以及IL-6的含量较对照组(A组)明显增加,吸入20 mg/L的NO后,肺组织中IL-6降低;吸入100mg/L的NO时,肺组织中IL-6、COX-2含量明显升高。结论吸入20 mg/L的NO,可以减轻肺损伤的程度,而吸入100 mg/L的NO,则使肺组织的IL-6、COX-2含量增加,加重肺损伤的程度。     

Mastic gum has no effect on Helicobacter pylori load in vivo

OBJECTIVE: To determine whether mastic gum suppresses or eradicates Helicobacter pylori infection in humans. PATIENTS AND METHODS: Nine patients with H. pylori infection, and without gastroduodenal ulceration, were recruited from day-case endoscopy lists and treated with mastic 1 g four times daily for 14 days. [13C]Urea breath tests (UBTs) were carried out immediately before, on day 15 and 5 weeks after treatment with mastic. RESULTS: Mastic had no effect on H. pylori status in any of the eight completed patients; all remained H. pylori positive by UBT with no change in delta scores [pre-treatment mean +/- s.e.m. 19.1 +/- 3.7, day 15 (post-treatment) 18.7 +/- 3.8, P = 0.8, paired t-test]. CONCLUSION: Despite reported anti-H. pylori action in vitro, this preliminary study shows that mastic has no effect on H. pylori in humans.     

新型脲分子吸附剂对急性肾衰竭动物血液灌流的影响

目的 :观察自制新型脲分子吸附剂 (IA )对急性肾衰竭模型动物进行血液灌流时对毒素清除及肾脏损伤修复的效果。方法 :选用日本纯种大耳白兔 ,以腹腔注射庆大霉素建立急性肾衰竭模型。用 IA 进行血液灌流 ,每次 2小时 ,30日为 1个观察周期。检测不同灌流时间的肾功能、电解质、免疫球蛋白及补体、γ谷氨酰转移酶 (γ GT)、N乙酰β氨基葡萄糖苷酶 (NAG) ,并对肾脏进行病理检查。结果 :急性肾衰竭模型动物经血液灌流 10日后 ,血尿素氮 (BUN )、肌酐 (Cr)接近正常 ;在每次灌流中 ,6 0分钟时 BU N接近正常 ,30分钟 Cr达正常 ;免疫球蛋白、补体、γ GT、NAG酶经灌流后均达正常水平 ,肾脏病理也有显著变化。结论 :IA 用于急性肾衰竭的灌流 ,能有效地清除毒素 ,具有低价、高效、快速的治疗效果     

Injurious ventilation strategies cause systemic release of IL-6 and MIP-2 in rats in vivo

In vivo experiments showed no increased production of tumour necrosis factor (TNF) in response to injurious ventilation strategies in otherwise untreated animals. Because interleukin-6 (IL-6) and macrophage inflammatory protein-2 (MIP-2) are more sensitive markers of ventilation-induced cytokine release, serum and bronchoalveolar lavage (BAL) samples were examined for these mediators. Eighty-five adult rats were randomized to three different ventilation strategies. Rats were ventilated with low pressures and low tidal volumes [13/3; peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP) in cmH2O], the second group of rats was ventilated with high pressures and low PEEP resulting in high tidal volumes (32/6), and the third group was ventilated with the same high pressures but without PEEP (32/0). Animals were ventilated either for 90 or 240 min, subsequently serum and BAL were collected for analyses on IL-6 and MIP-2 content. Non-ventilated animals served as healthy controls. Ventilation with 32/0 for 90 or 240 min, led to increased serum IL-6 levels. Serum MIP-2 levels were increased by ventilation with 32/6 (90 min) and 32/0 (240 min). Ventilation under any condition, even at 13/3, resulted in elevated MIP-2 levels in the BAL fluid. Even at normal pressures pulmonary MIP-2 levels were increased, suggesting that ventilation may promote pro-inflammatory responses in healthy subjects.     

Successful treatment of renovascular hypertension has no effect on insulin sensitivity

BACKGROUND: The association of insulin resistance (IR) and essential hypertension is well known, but a causal relationship has not been proven. Patients with secondary hypertension as a result of renal artery stenosis (RAS) usually do not reveal IR, but no study has addressed the effect of blood pressure reduction after successful treatment of RAS on insulin sensitivity and glucose effectiveness. PATIENTS AND METHODS: The insulin sensitivity index (SI) and glucose effectiveness (SG) were measured before and after successful intervention of an angiographically proven significant RAS in 18 out of 23 patients (eight males/10 females; mean age 51.5 +/- 13.1 years) in which improvement/cure of arterial hypertension was achieved. After a mean of 10.7 months, patients were reevaluated for 24-h blood-pressure measurement, kidney function, adrenaline, noradrenaline, plasma-renin-activity (PRA), aldosterone, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), and glucose metabolism parameters such as basal insulin, glucose disappearance constant (K-value), SI and SG. For calculation of SI and SG, insulin and glucose data from the modified frequent sampling intravenous glucose tolerance test (FSIGT) were submitted to the MINMOD program. RESULTS: After intervention, systolic 24-h blood pressure had decreased from 156.1 +/- 16.4 mmHg to 139.9 +/- 15.1 mmHg, and diastolic 24-h blood pressure from 97.1 +/- 14.7 mmHg to 87.3 +/- 13.4 mmHg. No significant change in SI (before 4.3 +/- 2.0, after 4.8 +/- 2.0 min(-1) per microU mL(-1)) or SG (before 1.55 +/- 0.42x10(-2) min(-1), after 1.8 +/- 0.48x10(-2) min(-1)) was observed. Aldosterone decreased from 246.7 +/- 180.7 to 115 +/- 61.4 (P=0.009) as PRA decreased from 12.4 +/- 11.4 to 4.2 +/- 7.6 ng mL h(-1) (P=0.01). Creatinine clearance, and adrenaline and noradrenaline levels as well as ANP and cGMP did not change after treatment for RAS. Subsequent to the definition of IR (SI < or =3.2x10(-4) min(-1) per microU mL(-1)) some differences among these two subgroups (SI < or =3.2, or SI>3.2) could be found. Patients with IR (n=8) were characterized by a higher body mass index (BMI), higher basal insulin values and significantly lower cGMP values. Only the group without IR (n=10) developed significant improvement of systolic blood pressure. CONCLUSION: We conclude that blood pressure reduction by treatment of RAS does not alter insulin action and that there is no link between the circulating concentrations of renin/aldosterone and glucose metabolism in renovascular hypertension (RVH). The results do not support the hypothesis of a direct link between blood pressure in RVH and the individual state of insulin sensitivity. However, patients with a normal SI are more likely to experience an almost normalization of arterial blood pressure after treatment for RAS.     

脑梗死患者血清白介素-6、白介素-8、肿瘤坏死因子-α及白介素-1β水平的研究

目的研究脑梗死患者急性期血清 IL -6、IL-8、TNF-α、IL -1β水平的变化 ,特别是 IL -6水平与脑梗死面积及神经功能缺损的关系。方法采用双抗体夹心 ELISA法检测 3 4例脑梗死急性期患者不同时间内血清 IL-6、IL -8、TNF-α、IL -1β水平 ,并随机抽取 10例健康人进行对照。结果脑梗死患者血清 IL -6水平在发病 6小时内明显升高 ,2 4～ 3 6小时达高峰 ,7天后基本降至正常 ,大面积梗死组IL-6水平明显高于小面积梗死组 ( 6小时内 ,P <0 .0 5 ;2 4～ 3 6小时 ,P <0 .0 5 ) ,且血清 IL -6水平与神经功能评分呈正相关( r=0 .87,P<0 .0 1) ,七叶皂甙钠治疗 3天后血清 IL-6水平下降明显 ( P<0 .0 1) ,脑梗死患者急性期血清 IL-8水平亦升高( P<0 .0 5 ) ,TNF-α、IL-1β水平则无明显变化。结论急性脑梗死患者血清 IL-6水平升高 ,而 IL-6升高的水平反映应激反应程度 ,与梗死面积及神经功能缺损程度有一定相关性。     

厄贝沙坦干预糖尿病肾病大鼠白细胞介素8、白细胞介素10的变化

目的观察厄贝沙坦干预对炎症相关细胞因子白细胞介素8(IL-8)和白细胞介素10(IL-10)水平的影响,并从炎症方面探讨其可能的药物作用机制。方法将36只Wistar大鼠随机分为右肾切除对照组、糖尿病肾病组(DN)、厄贝沙坦治疗组(Irb)3组,每组12只。第8周、12周末收集大鼠血、尿标本,测定血液IL-8I、L-10、血糖、肌酐、尿素氮、尿液24小时尿蛋白含量,同时测定肾质量/体质量比值。结果 Irb组和DN组8周、12周的IL-8均高于对照组,而DN组8周、12周的IL-8又高于Irb组(26.51±2.34)ng/L vs(16.12±2.11)ng/L,(59.32±1.28)ng/L vs(21.46±2.59)ng/L(P<0.01);Irb组和DN组12周均高于8周(21.46±2.59)ng/L vs(16.12±2.11)ng/L,(59.32±1.28)ng/L vs(26.51±2.34)ng/L(P<0.01);但Irb组上升幅度小于DN组。Irb组和DN组8周、12周的IL-10均低于对照组,而DN组8周、12周的IL-10又低于Irb组(21.27±2.49)ng/L vs(25.58±3.52)ng/L,(18.05±3.55)ng/L vs(33.22±2.97)ng/L(P<0.01);DN组12周的IL-10低于8周(18.05±3.55)ng/L vs(21.27±2.49)ng/L(P<0.01);而Irb组12周的IL-10高于8周(33.22±2.97)ng/L vs(25.58±3.52)ng/L(P<0.01);C组12周与8周的IL-8I、L-10无明显变化(P>0.05)。IL-8与IL-10显著负相关(r=-0.659,P<0.01);IL-8与血糖、24小时尿蛋白、肌酐、血尿素氮、肾质量/体质量比显著正相关(r=0.596、0.764、0.845、0.635、0.830,P<0.01),而IL-10与血糖、24小时尿蛋白、肌酐、血尿素氮、肾质量/体质量比显著负相关(r=-0.835、-0.739、-0.757、-0.745、-0.810,P<0.01)。结论厄贝沙坦通过抑制免疫炎症反应使促炎症细胞因子IL-8分泌减少,同时刺激分泌抗炎症细胞因子IL-10,改善DN大鼠肾脏肥大程度和尿蛋白排泄,起到保护肾脏的作用。     

芪玄益心胶囊对冠脉结扎大鼠心肌IL-1β及其mRNA表达的影响

目的评价芪玄益心胶囊对冠脉结扎大鼠心肌梗死的治疗作用,并探讨其机理。方法建立大鼠冠脉结扎心肌梗死模型,将模型大鼠随机分为麝香保心丸组、芪玄益心胶囊高、中、低剂量组、模型组,并设空白对照组。观察各组心肌梗死率和心肌白介素-1β(IL-1β)及其mRNA的表达。结果模型组及各治疗组与空白组比较心肌梗死率、IL-1β及其mRNA表达均显著增高(P<0.05)。芪玄益心胶囊各剂量组与模型组比较心肌梗死率、IL-1β及其mRNA均明显降低(P<0.05),以高剂量组变化最显著,高剂量组在降低心肌梗死率、IL-1β及其mRNA表达方面均优于麝香保心丸组(P<0.05)。结论芪玄益心胶囊能够降低心肌梗死率,并推测芪玄益心胶囊抗心肌梗死的作用与其抑制IL-1β及其mRNA的表达相关。     

The in vivo effect of interleukin-1β on urea synthesis is mediated by glucocorticoids in rats

Abstract. Interleukin-1 β has been proposed as one mediator of parts of the catabolic response following surgery. However, it is not known whether such an effect is due to interleukin-1 β itself or the associated changes in glucocorticoids.
The effect of interleukin-1 β on urea synthesis was investigated in rats given a high (10 μg kg^-1) and a low dose (0·1 μg kg^-1) of recombinant interleukin-1 β (NOVO, Denmark) 3 h prior to determination of the rate of urea synthesis in vivo . Urea synthesis increased dose-dependently after the low dose from 4·0±0·3 (control) to 6·3±0·3 ( P <0·01), and after the high dose to 7·7±0·3 μmol (min·100 gBW)^-1 ( P <0·01). The blood concentration of amino acids fell during interleukin-1 β treatment, so the effect on urea synthesis was not due solely to increased proteolysis, but was exerted predominantly in the liver.
Pharmacological glucocorticoid receptor blockade (hormone analogue RU486, Roussel–Uclaf, Paris, France) given 1 h prior to the interleukin treatment, completely abolished the interleukin-1 β induced increases in urea synthesis. The study demonstrates that interleukin-1 β stimulates urea synthesis in vivo , and that the major part of the effect depends on glucocorticoid action.     

分娩镇痛对产妇血清IL-6、IL-8、IL-1O水平的影响

目的 观察应用罗哌卡因连续硬膜外阻滞麻醉进行分娩镇痛对产妇血清中IL-6、IL-8、IL-10的影响.方法 选择200例产妇随机分为观察组(Ⅰ组)和对照组(Ⅱ组),每组100例.Ⅰ组在宫口开至2～3 cm时开始采用连续硬膜外阻滞麻醉方法进行分娩镇痛;Ⅱ组按产科常规处理.观察分娩镇痛前30 min、分娩镇痛后2h、分娩后24h、48 h和72 h五个时点患者血清中白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素- 10( IL- 10)水平的变化.结果 两组患者分娩镇痛后血清1L-6、IL-8、IL-10水平与分娩镇痛前值比较均升高(P＜0.01),一般在分娩后24 h达峰值.比较血清IL-6、IL-8、IL-10浓度变化,Ⅱ组较Ⅰ组升高更为明显(P＜0.05).结论 应用罗哌卡因连续硬膜外阻滞麻醉进行分娩镇痛可有效地降低产妇分娩后炎性应激反应.     

雷公藤多苷对白塞病患者血清细胞因子水平的影响

目的 探讨雷公藤多苷对白塞病患者血清细胞因子IL-4、IL-6、IL-8、IL-10水平的影响,进而从分子生物学水平探讨雷公藤多苷对白塞病的治疗作用及其可能的机制。方法 收集济宁医学院附属医院2007年6月至2009年6月门诊就诊的初治白塞病患者30例,给予雷公藤多苷片30 mg/d,疗程3个月,对照组为健康体检者30例。采用放免法测定白塞病患者接受雷公藤多苷治疗前后,以及对照组的血清细胞因子IL-4、IL-6、IL-8、IL-10的水平。并结合血沉、C-反应蛋白及临床表现等情况进行分析。结果 （1）白塞病患者治疗前血清IL-6、IL-8水平明显高于正常对照组（P＜0.05）, IL-4、IL-10水平较正常对照组无明显变化（P＞0.05）。（2）雷公藤多苷治疗3个月后患者血清IL-6、IL-8水平较治疗前明显减低（P＜0.05）, IL-4、IL-10水平较治疗前明显升高（P＜0.05）。（3）30例接受雷公藤多苷治疗的患者中,显效10例,有效16例,无效4例,有效率86.7%,治疗3个月后患者血沉、C-反应蛋白水平均较治疗前明显降低（P＜0.05）。结论 （1）白塞病患者血清IL-4、IL-6、IL-8、IL-10水平的失衡可能与其发病有关;（2）雷公藤多苷可有效调节白塞病患者血清IL-4、IL-6、IL-8、IL-10的水平,从而发挥其治疗作用。     

Bradykinin has no acute effect on the response of forearm blood flow to sympathetic stimulation in man

1. Six healthy male subjects received 0.9% (w/v) NaCl (saline) followed by incremental doses of bradykinin (1, 3 and 10 pmol/min), via the left brachial artery. Blood flow and the response of blood flow to lower-body negative pressure were measured in both forearms during infusion of saline and each dose of bradykinin. 2. Bradykinin produced a moderate and dose-dependent increase in blood flow in the infused, but not the non-infused, forearm. Lower-body negative pressure produced an approximately 15-20% reduction in blood flow in both forearms, and this response was unaffected by local infusion of bradykinin. 3. Bradykinin, in contrast to angiotensin II, had no acute effect on peripheral sympathetic responses to lower-body negative pressure. We conclude that, in forearm resistance vessels in man, withdrawal of angiotensin II, rather than accumulation of bradykinin, is likely to account for the attenuation of peripheral sympathetic responses after acute administration of a converting-enzyme inhibitor.     

Upregulation of IL-6, IL-8 and CCL2 gene expression after acute inflammation: Correlation to clinical pain

Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery model of tissue injury and acute pain. Tissue injury resulted in a significant upregulation in the gene expression of interleukin-6 (IL-6; 63.3-fold), IL-8 (8.1-fold), chemokine (C-C motif) ligand 2 (CCL2; 8.9-fold), chemokine (C-X-C motif) ligand 1 (CXCL1; 30.5-fold), chemokine (C-X-C motif) ligand 2 (CXCL2; 26-fold) and annexin A1 (ANXA1; 12-fold). The upregulation of IL-6 gene expression was significantly correlated to the upregulation of IL-8, CCL2, CXCL1 and CXCL2 gene expression. Interestingly, the tissue injury-induced upregulation of IL-6, IL-8 and CCL2 gene expression, was positively correlated to pain intensity at 3 h post-surgery, the onset of acute inflammatory pain. However, ketorolac treatment did not have a significant effect on the gene expression of IL-6, IL-8, CCL2, CXCL2 and ANXA1 at the same time point of acute inflammation. These results demonstrate that the upregulation of IL-6, IL-8 and CCL2 gene expression contributes to the development of acute inflammation and inflammatory pain. The lack of effect of ketorolac on the expression of these gene products may be related to the ceiling analgesic effects of non-steroidal anti-inflammatory drugs.