A randomized, double-blind, placebo-controlled pilot study of IV morphine-6-glucuronide for postoperative pain relief after knee replacement surgery

OBJECTIVES: To determine the dose-response effect of intravenous morphine-6-glucuronide (M6G) on acute postoperative pain. METHODS: Patients undergoing knee replacement surgery under spinal anesthesia were randomly assigned to 1 of 4 single intravenous M6G doses, 0 (placebo), 10, 20, or 30 mg/70 kg, administered 150 minutes after the spinal anesthetic was given. Analgesic effects were evaluated by determining the cumulative patient controlled analgesia (PCA) morphine dose, consumed over a 12 and 24 hours period, after the initial dose of M6G. For pain assessments, a 10 cm visual analog scale was used. RESULTS: Data from 41 patients were evaluated (n=10, 10, 10, and 11 in the 0, 10, 20, and 30 mg M6G groups). Only at the highest M6G dose (30 mg/70 kg), morphine PCA consumption was significantly less compared with placebo: over the first 12 postoperative hours mean PCA morphine consumption was 3.0+/-2.0 mg/h after placebo and 1.4+/-0.5 mg/h after 30 mg M6G (P=0.03); over the first 24 h mean PCA morphine consumption was 2.5+/-2.1 mg after placebo and 1.0+/-0.4 mg after 30 mg M6G (P=0.04) (mean+/-SD). Visual analog scale values were similar across all groups during these time periods. DISCUSSION: The analgesic effect of M6G in postoperative pain was demonstrated with 30 mg/70 kg M6G superior to placebo. At this dose, M6G has a long duration of action as determined by a reduction in the use of morphine PCA over 12 and 24 hours.     

The efficacy of preoperative versus postoperative rofecoxib for preventing acute postoperative dental pain: a prospective randomized crossover study using bilateral symmetrical oral surgery

BACKGROUND: Previous data have demonstrated that rofecoxib has good analgesic efficacy for acute postoperative dental pain. However, up to half of these patients require rescue analgesics within the first 24 hours. As the timing of analgesic interventions may be an important factor in pain control, the present study tested the hypothesis that rofecoxib administered preoperatively would improve the analgesic efficacy and reduce rescue analgesic requirements within the first 24 hours compared with postoperative administration. METHODS: This was a double-blind, randomized, crossover study where 45 patients had each of their identical impacted mandibular third molars removed under local anesthesia on 2 separate occasions. Patients acted as their own control; one side was pretreated with rofecoxib 50 mg, 2 hours before surgery, followed by placebo 15 minutes after surgery, and the contralateral side was pretreated with placebo 2 hours before surgery and posttreated with rofecoxib 50 mg 15 minutes after surgery. The difference in postoperative pain between 2 sides was assessed by 4 primary end-points: pain intensity as measured by a 100-mm visual analogue scale hourly for 12 hours, time to rescue analgesic, postoperative analgesic consumption, and patient's global assessment. RESULTS: Patients reported significantly lower pain scores (P = 0.04), longer time to rescue analgesic (P = 0.02), lesser postoperative analgesic consumption (P = 0.008), and better global assessment (P = 0.01) in the pretreated compared with the posttreated sides. There were significantly more patients in the pretreated group who did not required rescue analgesic within the first 24 hours (80% vs. 58%, P = 0.01), and the pain scores were extremely low in both groups during the 12 hours postoperative period (9.8 +/- 5.0 mm vs. 14.3 +/- 7.4 mm). CONCLUSION: Rofecoxib is an excellent analgesic for preventing postoperative dental pain and when given 2 hours preoperatively rendered most patients relatively pain free, requiring no rescue analgesics on the first postoperative day.     

The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double blind, placebo controlled study

The aim of this study was to assess if the pain of osteoarthritis is reduced by topical capsaicin and to determine whether addition of glyceryl trinitrate has an effect on analgesic efficacy and tolerability of capsaicin. A randomized, double blind, placebo controlled study was carried out on 200 adult patients attending a Pain Clinic with osteoarthritis pain. Patients applied one of four creams topically over the affected joint over a 6 week period. Creams contained either placebo (vehicle), 0.025% capsaicin, 1.33% glyceryl trinitrate or 0.025% capsaicin + 1.33% glyceryl trinitrate. Analgesic efficacy, tolerability of cream and analgesic consumption were assessed. One hundred and sixty-seven of 200 patients completed the study. Baseline visual analogue scores (0-10 scale) for pain were 6.40. There was a significant reduction in pain scores in the glyceryl trinitrate group (mean decrease 0.59, p< 0.05, 95% confidence limits 0.04-1.14), 0.025% capsaicin group (mean decrease 0.5, p< 0.05, 95% confidence limits 0.05-1.05) and the glyceryl trinitrate capsaicin group (mean decrease 1.1, p<0.05, 95% confidence limits 0.22-1.98). Baseline discomfort of application scores were similar for all but the capsaicin groups (they were significantly higher (by 2.1 units, p< 0.001)). The odds ratio in favour of continuing treatment was 2.1 (95% confidence limits 1.0-4.4) for glyceryl trinitrate and 2.4 (95% confidence limits 1.2-5.1) for capsaicin and 5.0 (95% confidence limits 3.8-6.4) for capsaicin GTN combination. The study showed that topical capsaicin and glyceryl trinitrate have an analgesic effect in painful osteoarthritis. When used together this effect is increased with the combination being more tolerable than capsaicin alone. Analgesic consumption is decreased by capsaicin, glyceryl trinitrate and to a greater extent by both combined.     

Anxiety-like behaviour in rats with mononeuropathy is reduced by the analgesic drugs morphine and gabapentin

Anxiety has been described as an important comorbidity in patients suffering from chronic pain. However, in animals the connection between persistent pain and anxiety has hardly been investigated. Therefore, in the current study it was assessed whether chronic pain also causes anxiety-like behaviour in animals and if it can be reversed by analgesic or anxiolytic drugs. Neuropathic pain was induced in rats by partial sciatic nerve ligation (PNL) and chronic constriction injury (CCI). Mechanical hypersensitivity was assessed by the "electronic algometer", while anxiety-like behaviour was measured by using the elevated plus maze. In both neuropathic pain models, rats exhibited mechanical hypersensitivity, whereas a significant increase in anxiety-like behaviour was observed only in CCI rats (time spent in open arms decreased significantly from 99+/-15.8s in sham animals to 33.4+/-7.5s in CCI animals). Furthermore, midazolam (0.5mg/kg; i.p.) significantly reduced anxiety-like behaviour in both sham- and CCI-operated animals without influencing mechanical hypersensitivity. Morphine (3mg/kg; i.p.) and gabapentin (30 mg/kg; i.p.) significantly attenuated anxiety-like behaviour in the CCI lesioned rats: morphine increased entries into open arms from 3.0+/-0.4 to 7.7+/-1.4 (P=0.01), gabapentin elevated this value from 4.7+/-1 to 7.5+/-0.9 (P=0.02). These data suggest that rats subjected to neuropathic pain models develop anxiety-like behaviour which can be reversed by appropriate analgesic treatment. Morphine and gabapentin had no anxiolytic-like effect in sham treated animals, thus their effect on anxiety-like behaviour in the neuropathic pain model is likely indirect via their anti-nociceptive properties.     

Catastrophizing: a risk factor for postsurgical pain

OBJECTIVE: This research was designed to test the hypothesis that presurgery "catastrophizing" would predict postsurgical pain and postsurgical analgesic consumption. METHODS: A sample of 48 individuals who underwent anterior cruciate ligament repair participated in the study. All participants completed the Pain Catastrophizing Scale (described by Sullivan et al in 1995) prior to surgery. Measures of pain (pain scores on a scale of 0-10) were obtained in the postanesthetic care unit, as well as 1, 2, and 7 days after surgery. Opioid and nonopioid analgesic consumption was tabulated while patients were in the hospital and after discharge. RESULTS: Results showed that the Pain Catastrophizing Scale was a significant predictor of acute postsurgical pain in the postanesthetic care unit (r = 0.48, P = 0.004 for maximum pain in the postanesthetic care unit). Maximum pain ratings in patients with high Pain Catastrophizing Scale scores (> median of 13) were 33% to 74% higher numerically than in patients with low Pain Catastrophizing Scale scores (< or = median), and the duration of moderate-severe pain (>3/10) was more prolonged (45 minutes versus 28 minutes in patients with high and low Pain Catastrophizing Scale scores, respectively; P < 0.05). The Pain Catastrophizing Scale was also predictive of pain with activity at 24 hours (r = 0.65 for pain on walking, P < or = 0.0001). The Pain Catastrophizing Scale did not predict postoperative analgesic use. CONCLUSION: The pattern of findings suggests that high catastrophizing scores may be a risk factor for heightened pain following surgery. Clinical and theoretical implications of the findings are addressed.     

Analgesic treatment and predictors of satisfaction with analgesia in patients with acute undifferentiated abdominal pain.

The objectives of this prospective, observational cohort study were to examine current practice of analgesia in adults with acute abdominal pain presenting to emergency department (ED), to assess patient-physician agreement on pain severity, and to measure patients' satisfaction with pain management. METHODS: Emergency room nurse assessed initial patient's and physician's ranking on a 0-100mm visual analogue scale (VAS) as well as patient's VAS rankings 5min, 15min, and 60min after starting treatment for pain, and on discharge. In patients who received no therapy VAS scores were assessed 5min, 15min, and 60min after initial examination, and on discharge. Patient's satisfaction with pain management on discharge from ED was assessed using a four-point categorical scale in which 1=completely unsatisfied, 2=mostly unsatisfied, 3=mostly satisfied, and 4=completely satisfied. RESULTS: A total of 185 patients were enrolled. Patients' mean initial VAS was higher than physicians' (76+/-20mm, vs. 59+/-20mm, p<0.001). Physician's VAS > or = 60mm was the sole independent predictor of receiving analgesic therapy (p<0.001). On discharge from ED, 111 patients (60%) were predominantly satisfied with analgesia (satisfaction score > or = 3). Drug titration (p=0.026) and decrease in VAS score > or = 20mm between initial and discharge score (p<0.001) independently predicted patients' satisfaction. CONCLUSIONS: Patients with acute abdominal pain rated pain significantly higher than physicians who's pain estimation in turn tailored analgesia. Only 60% of patients were satisfied with analgesia. Analgesic drug titration and a decrease of > or = 20mm on VAS predicted patients' satisfaction.     

Increase in human platelet alpha 2-adrenergic receptor affinity for agonist in unstable angina

Spontaneous increase in platelet activity and change in coronary vasomotor tone have been implicated in the pathogenesis of acute myocardial ischemia. To define the mechanism of platelet "hypersensitivity" in acute myocardial ischemia, we examined the status of platelet alpha 2-adrenergic receptors in patients hospitalized with severe unstable angina. With the use of the specific alpha 2-receptor antagonist 3H-yohimbine, we identified a 26% decrease in the receptor binding sites on platelet membranes from patients with unstable angina compared with controls (155 +/- 32 vs. 210 +/- 29 fmol/mg protein, P less than or equal to 0.005). The dissociation constants of 3H-yohimbine binding to platelet alpha 2-receptors were similar in both groups (3.3 +/- 1.1 and 4.1 +/- 1.6 nmol/L, P not significant). To study the alterations in the affinity of platelet alpha 2-receptors for the agonists, effects of 1-epinephrine on specific binding of 3H-yohimbine were examined. We observed a marked reduction in 1-epinephrine concentration for inhibition of antagonist binding by 50% in acute myocardial ischemia (IC50: 4.2 +/- 3.9 X 10(-8) vs. 6.7 +/- 3.4 X 10(-7) mol/L, P less than or equal to 0.01), indicating increase in platelet alpha 2-receptor affinity for the agonist. Platelet aggregation and thromboxane A2 generation in response to epinephrine were also significantly increased in the acute phase of myocardial ischemia. This study suggests enhanced affinity of platelet alpha 2-receptors to the agonist 1-epinephrine as a possible mechanism of platelet hypersensitivity in acute myocardial ischemia.     

脑梗死后神经功能缺损程度与血管性痴呆发生关系的研究

目的探讨脑梗死后神经功能缺损程度(ND)与血管性痴呆(VD)发生的关系。方法对43例脑梗死、33例有脑卒中危险因素病人和30例年龄匹配正常人进行简易智力状态试验(MMSE)、认知能力筛选试验(CCSE)和听觉ERP测试。结果脑梗死组MMSE、CCSE和ERP的N2和P3峰潜伏期(PL)均与危险因素组和正常对照组有显著性差异(P<0.01),后两组的N2PL和P3PL亦有显著性差异(P<0.05)。轻度和中度脑梗死组的MMSE和CCSE得分无显著性差异(P>0.05),但两组间P3PL差异显著(P<0.01),而且ND得分与P3PL呈显著正相关(r=“0.373,P<“0.02)。脑梗死组MMSE、CCSE和P3PL和异常率分别为21％、37％和49％3者之间的差异均有显著性(P<0.05)。脑梗死的部位的数量对MMSE、CCSE、ERP和P3PL未见明显影响。结论ND与卒中后认知障碍有关,与P3PL呈显著正相关,脑梗死灶的部位、数量在VD的发生中作用不大。     

夜来香提取物对小鼠的镇痛作用

背景:夜来香水提取物具有抗心律失常、局部麻醉以及中枢抑制作用。目的:探讨夜来香提取物对小鼠的镇痛作用,为临床疼痛治疗寻找新药。设计:随机对照观察。单位:赣南医学院现代教育中心与药理教研室。材料:实验于2005-03/04在赣南医学院科研中心实验室完成。①选取健康成年昆明种小鼠150只用于以下4个独立实验。②药品:夜来香提取物由沈阳药科大学植化教研室提供(药品批号:2002080901);盐酸吗啡注射液(沈阳第一制药厂,批号000305);盐酸纳洛酮注射液眼盐侨(湖南)制药有限公司,批号20021109演。方法:①夜来香提取物对醋酸引起小鼠扭体反应的实验:小鼠40只,随机数字表法分为4组,10只/组,分别腹腔注射0.02mL/g生理盐水,0.10,0.20mg/g夜来香提取物,0.10mg/g氨基比林。15min后腹腔注射6g/L冰醋酸0.01mL/g,观察记录15min内各组小鼠扭体反应次数。②夜来香提取物对小鼠热板法致痛作用的实验:雌性小鼠40只,随机数字表法分为4组,10只/组,分别腹腔注射0.02mL/g生理盐水,0.10,0.20mg/g夜来香提取物,0.01mg/g吗啡,用热板法测定给药后15,30,60min的痛觉反应。③纳洛酮拮抗吗啡、夜来香提取物对小鼠热板法致痛作用的实验:雌性小鼠30只,随机数字表法分为3组,10只/组,分别腹腔注射0.02mL/g生理盐水,0.004mg/g纳洛酮 0.01mg/g吗啡,0.004mg/g纳洛酮 0.10mg/g夜来香提取物,热板法测定给药后15,30,60min的痛觉反应。④夜来香提取物对电刺激致痛的实验:小鼠40只,随机数字表法分为4组,10只/组,分别腹腔注射0.02mL/g生理盐水,0.10,0.20mg/g夜来香提取物,1g/L吗啡,于给药后20,35,50,70min重复电刺激,电刺激法测定痛觉反应。主要观察指标:①小鼠扭体反应次数。②热板法致小鼠痛觉反应的时间。③电刺激法致小鼠镇痛率。结果:共选取健康成年昆明种小鼠150只用于4个独立实验,全部进入结果分析。①小鼠扭体反应次数:0.10,0.20mg/g夜来香提取物及0.10mg/g氨基比林对醋酸诱发小鼠扭体反应有非常显著的镇痛作用,给药后扭体反应次数均少于生理盐水组(20.2±10.8,14.5±7.6,7.6±4.5,50.6±15.5,P<0.01),且夜来香提取物的镇痛效果呈剂量依赖性。②热板法致小鼠痛觉反应的时间:0.10,0.20mg/g夜来香提取物对热板致痛有显著的镇痛作用,给药后15,30,60min痛觉反应的时间均长于生理盐水组(P<0.05或0.01),且呈剂量依赖性。纳洛酮0.004mg/g 夜来香提取物0.10mg/g组给药后各时间点痛觉反应的时间均长于生理盐水组(P<0.05或0.01),但纳洛酮0.004mg/g 吗啡0.01mg/g组与生理盐水组相接近。③电刺激法致小鼠镇痛率:夜来香提取物0.10,0.20mg/g组及吗啡组给药后20,35,50,70min镇痛率均高于生理盐水组(P<0.01)。结论:夜来香提取物具有明显的镇痛作用,且镇痛强度呈剂量依赖性。其镇痛作用并非通过激动阿片受体而实现的。     

Effects of the 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid/kainate antagonist LY293558 on spontaneous and evoked postoperative pain

BACKGROUND: Previous studies suggest that 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA)/kainate antagonists reduce experimentally induced pain. There have been no studies of AMPA/kainate antagonists in clinical pain. METHODS: Analgesic efficacy of intravenous LY293558 (0.4 or 1.2 mg/kg) was compared with that of intravenous ketorolac tromethamine (INN, ketorolac; 30 mg) and placebo in a randomized, double-blind, parallel-group study after oral surgery (n = 70). Study drugs were administered at the onset of moderate pain; pain intensity and relief were measured for 240 minutes. RESULTS: High-dose LY293558 and ketorolac tromethamine were superior to placebo (P < .05) for pain evoked by mouth opening and one of several measures of spontaneous pain: SPID240 +/- SEM for pain evoked by mouth opening was highest for ketorolac tromethamine (151 +/- 58), intermediate for high-dose LY293558 (-45 +/- 35), and least for low-dose LY293558 (-151 +/- 39) and placebo (-162 +/- 50). High-dose LY293558 was superior to placebo at individual time points (45 to 240 minutes) for pain evoked by mouth opening but not for spontaneous pain. The spontaneous summed pain intensity difference over 240 minutes (SPID240 +/- SEM) was highest for ketorolac tromethamine (303 +/- 84), intermediate for high-dose LY293558 (-51 +/- 40) and low-dose LY293558 (-96 +/- 45), and least for placebo (-180 +/- 24). LY293558 was well tolerated, with dose-dependent and reversible side effects including hazy vision in 20% of patients and sedation in 15%. CONCLUSIONS: This is the first evidence that an AMPA/kainate antagonist reduces clinical pain. Tests of evoked pain may be more sensitive to certain analgesics than those of spontaneous pain. The evaluation of evoked pain as an outcome measure in analgesic trials may identify potentially useful compounds otherwise missed if only spontaneous pain is evaluated.     

The use of methylphenidate in patients with incident cancer pain receiving regular opiates. A preliminary report.

In this open, uncontrolled trial, 15 patients with severe incident cancer pain receiving regular opiates were administered 10 mg oral methylphenidate (MP) at 08.00 h and 15 mg at 12.00 h in order to antagonize opiate-induced sedation. The daily dose of opiate was increased by 30% 24 h after starting MP, followed by a 10% increase twice a day until maximal tolerated dose. In 14 evaluable patients, pain (VAS 0-100 mm), sedation (VAS), and mean equivalent daily dose (MEDD) of morphine were 55 +/- 17, 65 +/- 18 and 248 +/- 150 48 h before MP, versus 38 +/- 12 (P less than 0.01), 42 +/- 12 (P less than 0.01), and 405 +/- 130 (P less than 0.01) 48 h after MP, respectively. After 48 h of treatment, 12 of 14 patients felt better on MP, 2 of 12 patients felt no difference, and no patients felt worse (P less than 0.05). We conclude that the addition of MP allowed for an increase in the MEDD of morphine and increased pain control. Controlled double-blind trials should be performed.     

Insulin and amylin release are both diminished in first-degree relatives of subjects with type 2 diabetes

OBJECTIVE: To determine whether first-degree relatives of individuals with type 2 diabetes, who are at high risk of subsequently developing hyperglycemia, manifest alterations in beta-cell function including an alteration in the co-release of insulin and amylin. RESEARCH DESIGN AND METHODS: In 30 first-degree relatives and 24 matched subjects with no family history of diabetes, beta-cell function was measured as the intravenous glucose-induced acute insulin response (AIR(g)) and acute amylin response (AAR(g)). The insulin sensitivity index (S(I)) was quantified and used to account for the role of insulin sensitivity to modulate beta-cell function (S(I) x beta-cell function). RESULTS: Fasting plasma glucose (5.3 +/- 0.1 vs. 5.1 +/- 0.1 mmol/l; means +/- SEM), immunoreactive insulin (IRI) (68 +/- 7 vs. 57 +/- 6 pmol/l) and amylin-like immunoreactivity (ALI) (5.5 +/- 0.6 vs. 4.7 +/- 0.7 pmol/l) were similar in relatives and control subjects, respectively. Relatives were insulin resistant compared with control subjects (S(I): 4.86 +/- 0.63 vs. 7.20 +/- 0.78 x 10(-5) min(-1). pmol(-1). l(-1), P = 0.01), but their AIR(g) (392 +/- 59 vs. 386 +/- 50 pmol/l) and AAR(g) (5.9 +/- 0.9 vs. 6.1 +/- 0.8 pmol/l) did not differ. When beta-cell function was determined relative to insulin sensitivity, in the first-degree relatives, both AIR(g) (S(I) x AIR(g): 1.60 +/- 0.23 vs. 2.44 +/- 0.31 x 10(-2) min(-1), P < 0.05) and AAR(g) (S(I) x AAR(g): 2.39 +/- 0.35 vs. 4.06 +/- 0.56 x 10(-4) min(-1), P < 0.05) were reduced. The molar proportion of ALI to IRI was not altered in high-risk subjects (1.75 +/- 0.16 vs. 1.71 +/- 0.15%). CONCLUSIONS: First-degree relatives of subjects with type 2 diabetes have diminished beta-cell function at a time when they are not hyperglycemic, and this reduction affects insulin and amylin responses proportionally. Thus, an altered amylin-to-insulin ratio is not likely to identify individuals at high risk of developing type 2 diabetes.     

认知障碍患者血清超氧化物歧化酶和同型半胱氨酸水平及其与认知功能相关性

目的探讨阿尔茨海默病(AD)与血管性认知障碍(VD)患者血清超氧化物歧化酶(SOD)、同型半胱氨酸(Hcy)水平及两者水平与认知功能的相关性。方法分析44例阿尔茨海默病患者的临床资料,列为AD组,选取43例血管性认知障碍患者作为对照组,分析两组SOD和Hcy水平的差异及与认知功能的相关性。结果AD组患者简易智力状况检查法(MMSE)评分明显高于VD组患者,差异有统计学意义(t=2.617,P=0.011)。两组研究对象在Mo CA(t=1.835,P=0.069)、ADL评分(t=0.971,P=0.334)比较上,差异无统计学意义(P0.05);AD组患者血清中SOD水平明显高于对照组,差异有统计学意义(t=2.485,P=0.015)。AD组患者血清中Hcy水平显著低于对照组,差异有统计学意义(t=6.635,P0.01)。两组研究对象血清CRP水平比较上,差异无统计学意义(t=0.902,P=0.369);AD组患者血清中Hcy与MMSE评分呈现显著的负相关(r=-0.795,P0.01),VD组患者血清中Hcy与MMSE评分也呈负相关(r=-0.758,P0.01)。两组研究对象血清中SOD与MMSE不存在明显的相关关系(r=0.211,P=0.152;r=0.185,P=0.241)。结论血清中SOD及Hcy水平改变可能参与了AD和VD相关发病机制,其中Hcy可作为预测AD、VD患者发生认知损伤的参考指标。     

Effects of electroacupuncture on intraoperative and postoperative analgesic requirement

Acupuncture has been shown to be effective in experimental and clinical acute pain settings. This study aims to evaluate the effect of preoperative electroacupuncture (EA) on intraoperative and postoperative analgesic (alfentanil and morphine) requirement in patients scheduled for gynaecologic lower abdominal surgery. Ninety patients were randomly assigned to one of three groups: Group I (control group)--received placebo EA for 45 minutes before induction of general anaesthesia (GA); Group II--preoperative EA instituted 45 minutes before induction of GA; Group III--45 minutes of postoperative EA. The Bispectral Index monitor was used intraoperatively to monitor the hypnotic effect of anaesthetic drugs, and alfentanil was titrated to maintain the blood pressure and pulse rate within +/- 15% of basal values. Postoperative pain was managed by intravenous morphine via a patient-controlled analgesia (PCA) device. Patients in Group II (0.44 +/- .15microg/kg/min) received less alfentanil than those in Group III (0.58 +/- .22 microg/kg/min) (p = p.024), but not significantly less than those in Group I 10.51 +/- 0.21 microg/kg/min) (p = 0.472). Postoperative morphine consumption was numerically lower in Group II compared with the other groups; however, the difference was statistically significant only during the period of 6-12 hours between Group II [0.03 (0.05) mg/kg] and Group I [0.10 (0.11) mg/kg] (p = 0.015), and Group II and Group III [0.08 (0.10) mg/kg] (p = 0.010). The 24-hour cumulative morphine consumption for Group II (0.52 +/- .19mg/kg) was less than that for either Group I I0.68 +/- 38mg/kg) or Group III (0.58 +/- .27mg/kg), but the difference did not reach significance. In conclusion, preoperative EA leads to a reduced intraoperative alfentanil consumption, though this effect may not be specific, and has a morphine sparing effect during the early postoperative period.     

Effects of presurgical local infiltration of bupivacaine in the surgical field on postsurgical wound pain in laparoscopic gynecologic examinations: a possible preemptive analgesic effect

OBJECTIVE: A randomized, double-blind, controlled study was designed to evaluate the effect of presurgical local infiltration of bupivacaine in the surgical field on postsurgical wound pain relief and analgesic requirements in 28 healthy patients scheduled for laparoscopic gynecologic examinations. INTERVENTIONS: After induction of general anesthesia by routine methods, the patients were randomly divided into two groups. In the bupivacaine (B) group (n = 15), patients were injected with 5 ml of 0.25% bupivacaine at each incisional area (four sites, total of 20 ml) approximately 15 minutes before skin incision. In the control (C) group (n = 13), the surgical field was injected with an equal volume of physiologic saline solution (four sites, total of 20 ml). OUTCOME MEASURES: Postsurgical wound pain at rest was evaluated by a 10-cm visual analog pain scale at 1, 10, 24, and 72 hours and 1 month after surgery. The patients were interviewed via telephone 1 month after hospital discharge for re-evaluation of resting pain. RESULTS: The results indicated that the incidence of postsurgical wound pain for up to 10 hours after surgery in group B was significantly lower (p < 0.05) than in group C. Pain intensity ranged from mild to moderate (2-5 cm). In addition, the mean visual analog pain scale pain intensity was significantly less for group B (0.31 +/- 0.85 cm) than for group C (2.62 +/- 2.06 cm) for up to 10 hours after surgery (p < 0.05). The number of patients who requested analgesics and complained of sleep disturbances was significantly higher in group C (p < 0.05). The mean cumulative dose of diclofenac sodium at 24 hours was significantly (p < 0.05) lower in group B (6.67 +/- 17.6 mg) than in group C (30.8 +/- 25.3 mg). Prolonged postsurgical wound pain persisting 1 month after surgery was observed in one patient in group C. CONCLUSIONS: It is concluded that presurgical infiltration of 0.25% bupivacaine in the surgical field is a useful method for decreasing postsurgical wound pain for up to 10 hours and analgesic consumption for up to 24 hours after laparoscopic gynecologic examination.     

Local and Systemic Release of Cytokines,Nerve Growth Factor,Prostaglandin E2, and Substance P in Incisional Wounds and Serum Following Cesarean Delivery

The objectives of this study were to test the feasibility of measuring inflammatory and nociceptive biochemical mediators at the surgical site and to evaluate the relationship between wound and serum levels as well as determine any associations between mediator release, pain, and analgesic consumption after cesarean delivery. Twenty healthy women undergoing elective cesarean delivery with spinal anesthesia were enrolled. Wound exudate and serum mediators, pain scores, and analgesic consumption were measured at 1, 6, 24, and 48 hours after cesarean. In wound exudate, 19 of 20 mediators were reliably detected including interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor-α, interferon-γ, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1 (MIP-1β), nerve growth factor (NGF), prostaglandin E2 (PG-E2), and substance P. Wound PG-E2 and various cytokines peaked early, whereas NGF showed a more delayed release. There were no correlations between the concentration versus time profile of wound and serum cytokines. Analgesic consumption during the first 24 hours after surgery was negatively correlated with IL-1β, IL-6, and G-CSF in the wound exudate. This study demonstrates the feasibility of collecting and measuring nociceptive and inflammatory mediators in surgical wounds at specific time points. The lack of significant correlations between wound and serum levels emphasizes the importance of determining site-specific release if localized pathologies are to be studied.PerspectiveThis study demonstrates the feasibility of measuring real-time nociceptive and inflammatory mediators in surgical wounds. Our findings confirm the lack of correlation between wound and serum levels of many pro-inflammatory and anti-inflammatory cytokines and nerve growth factor.     

The analgesic effect of low dose focal irradiation in a mouse model of bone cancer is associated with spinal changes in neuro-mediators of nociception

Despite the widespread use of radiotherapy to treat painful bone metastases, the mechanism underlying the analgesic effect of low dose ionizing radiation is unknown. Bone cancer pain is mostly associated with an inflammatory response dominated by local activation of osteoclasts and by astrogliosis in the spinal cord. We determined the effects of a 6 Gy irradiation given focally on osteolytic sarcoma cells inoculated in humeri of mice. Pain behavior was assessed using the rota-rod and the grip force test. Seven days post-irradiation (day 17 post-tumor implantation) the performance of mice markedly improved on the rotarod (non-irradiated, 67+/-16s vs irradiated, 223 +/- 22 s; P = 0.0005), and the grip force test (non-irradiated, 34 +/- 4 g vs irradiated, 55 +/- 2 g; P = 0.001). This improvement was similar to the analgesia achieved with 30 mg/kg of the cyclooxygenase (COX) inhibitor ketorolac (Rota-rod, 67 +/- 16 s vs 178 +/- 35 s; P = 0.01: grip force test, 34 +/- 4 g, vs 60 +/- 5 g; P = 0.003). Following irradiation, the tumor mass and the number of osteoclasts did not decrease while the expression of two pro-inflammatory cytokines (monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha) increased. Tumor irradiation led to clear differences in the spinal cord. These include a decrease in glial activity (astrocytes and microglial cells) as well as pain mediators such as dynorphin, COX-2 and chemotactic cytokine receptor (CCR2). We conclude that the analgesic effect of low dose irradiation of bone cancer is associated with the alteration of nociceptive transmission in the central nervous system.     

Blood cell filtrability: reference values and clinical applications

In 500 healthy individuals cell deformability, expressed as cell filtration rate in microliters/s was studied with a microcirculation method in order to determine reference values for this method for various age groups in adults. The overall normal red cell filtration rate (RFR) value in healthy individuals was 69 +/- 11 microliters/s. When one compared the age groups 20-29 and 60-69 years, the reductions for RFR, white cell filtration rate (WFR), plasma-white cell filtration rate (P-WFR) and whole-blood filtration RATE (WBFR) was 26 +/- 3 (p less than 0.01), 32% +/- 5 (p less than 0.01), 28% +/- 4 (p less than 0.01) and 28% +/- (p less than 0.01) respectively. The reduction of RFR was graded into four clinical classes (GCTA = Gothenburg Cardio-Thoracic Association); I = 1-24%, II = 25-49%, III = 50-74%, IV = 75-100%, class I with lowest and class IV with highest reductions. Significant reductions in the mean RFR were noted in patients undergoing heart surgery (36% +/- 3, P less than 0.01, class II), patients with cardiac arrest (55% +/- 5, p less than 0.01, class III), occlusive arterial disease (58% +/- 6, p less than 0.001, class III) diabetes (45% +/- 5, p less than 0.01, class II). None of the patients had a normal RFR value. This study demonstrated a loss of cell deformability with age and disease.     

Preoperative oral administration of fast-release morphine sulfate reduces postoperative piritramide consumption

The aim of this prospective randomized placebo-controlled double-blind study was to investigate the effect of premedication with morphine sulfate on postoperative pain. Ninety-eight ASA I-III patients undergoing total replacement of the knee or hip joint were randomly assigned to one of two groups. Group 1 received 20 mg morphine sulfate p.o. approximately one hour before the start of surgery; group 2 received placebo. After surgery, piritramide was administered via patient-controlled analgesia over 24 hours. Piritramide consumption and pain scores (visual analog scale) were recorded. The duration of surgery (mean +/- SD) was comparable in the two groups (group 1: 145 +/- 42 min, group 2: 131 +/- 35 min). In group 1 the cumulative piritramide consumption during 24 hours postoperation was significantly less than in the placebo group (37.5 +/- 12.5 mg versus 46.8 +/- 22.1, t-test, p < 0.05), although similar pain scores were recorded (group 1: 4.8 +/- 1.8 and 3.6 +/- 1.7, group 2: 4.8 +/- 1.6 and 3.4 +/- 2.0, at 1 and 24 hours, respectively). These data show that the preoperative oral administration of morphine sulfate, regardless of its short half-life, can reduce postoperative consumption of opioids at similar pain levels.