Placebo Analgesia: Clinical considerations

Pain is the predominant symptom that prompts patients to seek medical advice and treatment from physiotherapists. Various treatment modalities such as heat and cold, electrical stimulation (Cheing and Hui-Chan, 1999), ultrasound, manipulative techniques, massage and laser treatment have been demonstrated in varying degrees to be clinically effective for managing pain of different pathologies. However, all these treatments could be assumed to have some placebo elements (French, 1994).

From a research design perspective, the presence of placebo response is undesirable and must be controlled as it complicates the demonstration of ‘real' treatment effect. From a clinical perspective, it is intriguing to note that the condition of patients in the placebo control groups did improve considerably in many of these validation studies, although in the majority the improvement was not so marked as in the treatment groups. Conspicuously, some neuro-physiological and psychological aspects of the placebo effects may have clinical use in enhancing the effect of pain treatments and their outcomes.

Unfortunately, although placebo response has been a subject of continuing interest among some physiotherapy researchers and clinicians, information about placebo analgesia and its clinical utility is seldom discussed. The purpose of this paper is to provide clinicians with an overview of the construct and research related to placebo analgesia as well as a discussion of the potential clinical use of certain components of placebo analgesia to enhance pain rehabilitation outcomes in physiotherapy practice.     

低氧暴露对运动性贫血大鼠抗氧化能力的影响

目的:观察低氧暴露对运动性贫血大鼠某些抗氧化酶的影响,探讨低氧条件下抗氧化系统的反应是否有利于改善运动性贫血。方法:实验于2005-07/09在广东省高等学校运动生物化学教学重点实验室完成。选择6周龄健康雄性SD大鼠40只,均为运动性贫血动物模型,大鼠适应环境1周后采用6周递增负荷跑台运动方式建立。按随机数字表法分为1h低氧暴露组、2h低氧暴露组和间歇性低氧暴露组、常氧恢复组,每组10只。采用人工常压低氧环境,低氧浓度控制在14.5%左右,按分组每天在常压低氧舱进行1,2h和间歇性低氧暴露(低氧暴露1h,中间间歇3h,再低氧暴露1h),其余时间在舱外常氧中自由活动,每周6d,持续3周。常氧恢复组大鼠在常氧中自由活动。3周后测试运动性贫血大鼠血清丙二醛含量、超氧化物歧化酶活性和血浆过氧化氢酶、谷胱甘肽过氧化酶活性。结果:纳入动物40只,均进入结果分析。①低氧暴露3周后1h低氧暴露组、2h低氧暴露组、间歇性低氧暴露组血清丙二醛含量均显著低于常氧恢复组[分别为(2.62±0.16),(2.60±0.22),(2.55±0.06),(3.36±0.34)μmol/L,P<0.05]。②低氧暴露3周后血清超氧化物歧化酶和血浆谷胱甘肽过氧化酶、过氧化氢酶活性均高于常氧恢复组,2h低氧暴露组与常氧恢复组比较差异有显著性意义[分别为(4239.68±169.53),(3190.30±339.40)μkat/L;(20622.46±2002.07),(15556.44±607.79)μkat/L;(50.01±6.67),(35.17±4.50)μkat/L,P<0.05]。③各低氧暴露组间除2h低氧暴露组血清超氧化物歧化酶活性显著高于1h低氧暴露组外[分别为(4239.68±169.53),(2126.41±161.20)μkat/L,P<0.05],其他指标组间差异无显著性意义(P>0.05)。结论:低氧暴露可提高运动性贫血大鼠机体的抗氧化能力,有利于促进运动性贫血的恢复。     

Cholesterol reduction by methyl-beta-cyclodextrin attenuates the delta opioid receptor-mediated signaling in neuronal cells but enhances it in non-neuronal cells

Opioid receptors have been shown to be located in and regulated by lipid rafts/caveolae in caveolin-rich non-neuronal cells. Here, we found that caveolin-1 level was very low in rat brain and undetectable in NG108-15 cells, which endogenously express delta opioid receptors (DOR). Rat caudate putamen (CPu) membranes, NG108-15 cells and CHO cells stably transfected with FLAG-mouse-DOR (CHO-FLAG-mDOR) were homogenized, sonicated in a detergent-free 0.5M Na(2)CO(3) buffer and fractionated through discontinuous or continuous sucrose density gradients. About 70% of opioid receptors in CPu and DOR in both cell lines were present in low-density (5-20% sucrose) membrane domains enriched in cholesterol and ganglioside M1 (GM1), characteristics of lipid rafts in plasma membranes. In both cells, stimulation with permeable or non-permeable full agonists, but not with partial or inverse agonists, for 30min shifted approximately 25% of DORs out of rafts, by a naloxone-reversible and pertussis toxin-insensitive mechanism, which may undergo internalization. Methyl-beta-cyclodextrin (MCD) treatment greatly reduced cholesterol and shifted DOR to higher density fractions and decreased DPDPE affinities. MCD treatment attenuated DPDPE-induced [(35)S]GTPgammaS binding in CPu and NG108-15 cells, but enhanced it in CHO-FLAG-mDOR cells. In CHO-FLAG-mDOR cells, G(alphai) co-immunoprecipitated with caveolin-1, which was shown to inhibit G(alphai/o), and MCD treatment dramatically reduced the association leading to disinhibition. Thus, although localization in rafts and agonist-induced shift of DOR are independent of caveolin-1, lipid rafts sustain DOR-mediated signaling in caveolin-deficient neuronal cells, but appear to inhibit it in caveolin-enriched non-neuronal cells. Cholesterol-dependent association of caveolin-1 with and the resulting inhibition of G proteins may be a contributing factor.     

Regulator of G protein signaling proteins differentially modulate signaling of mu and delta opioid receptors

Effects of regulator of G protein signaling (RGS) proteins on mu and delta opioid receptors were investigated in HEK293 cells. Co-expression of RGS1, RGS2, RGS4, RGS9, RGS10 or RGS19 (Galpha-interacting protein (GAIP)) significantly reduced [Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol]-Enkephalin (DAMGO)-induced inhibition of adenylyl cyclase (AC) mediated by mu opioid receptor, but only RGS9 decreased the effects of [Tyr-D-Pen-Gly-p-Chloro-Phe-D-Pen]-Enkephalin (DPDPE) mediated by delta opioid receptor. When C-tails of the receptors were exchanged (mu/deltaC and delta/muC chimeras), RGS proteins decreased delta/muC-mediated AC inhibition, but none had significant effects on that via mu/deltaC receptor. Thus, the C-terminal domains of the receptors are critical for the differential effects of RGS proteins, which may be due to differences in receptor-G protein-RGS protein interactions in signaling complexes.     

木贼提取物对小鼠脑心肺过氧化脂质产生的影响

木贼水醇提取物对小鼠过氧化脂质的产生有明显抑制作用。该提取物能减少体外与体内实验小鼠脑、心、肺匀浆中MDA含量,并随剂量的增加作用增强。提示木贼水醇提取物可能具有抗衰老作用。     

Intracerebroventricular treatment with an antisense oligodeoxynucleotide to κ-opioid receptors inhibited κ-agonist-induced analgesia in rats

In vivo treatment with an antisense (AS) phosphorothioate oligodeoxynucleotide (oligo) to the rat κ-opioid receptor selectively inhibited κ-mediated analgesia in the rat cold-water tail-flick test. Intracerebroventricular (i.c.v.) AS oligo significantly inhibited the analgesic effect of i.c.v. spiradoline, but not that of μ- or δ-opioid agonists. The dose-effect curve for s.c. spiradoline was shifted to the right after AS, but not missense or sense oligo treatment. Thus, AS oligos provide another technique with which to selectively manipulate opioid receptors and further support the role of non-μ opioid receptors in mediating analgesia in rats.     

多索茶碱在大鼠体内的药代动力学

为全面了解多索茶碱在大鼠体内代谢情况,用高效薄层色谱法和光密度扫描法,给大鼠ig多索茶碱后,测定在不同时间各组织和体液中多索茶碱的含量。结果表明,多索茶碱在大鼠体内药代动力学为一室模型并能在体内迅速转化为其它代谢产物。T_1/2(Ke)为1.17～3.75h,达峰时间T(peak)为0.72～1.46h,Cmax,AUC及CL/F呈剂量依赖关系。给药1h,以胃壁浓度最高,8h除胃肠组织浓度降低较慢外,其它组织中药物浓度明显降低。尿、粪及胆汁中原形药总排出量占给药量的5.2%。血浆蛋白结合率约25%。提示多索茶碱在体内可能转化为其它代谢产物。     

血管黏附分子中选择素结构、功能及其表达的特点

目的:归纳总结选择素的组成、分布、结构、表达及其选择素与配体相互作用的主要功能。资料来源:应用计算机检索Medline数据库1990-01/2007-01有关选择素功能的相关文章,检索词“Selectin,function”,限定文章语言种类为英文。同时计算机检索中国期刊全文数据库、万方数据库1994-01/2007-01期间的选择素的相关文章,检索词“选择素、功能”,限定文章语言种类为中文。资料选择:对资料进行初审,选取与选择素研究进展相关文献,然后筛除明显无关文献或相关性不强的文献,对剩余文献开始查找全文,进一步明确其相关性。纳入标准:随机对照研究;实验或临床研究包含平行对照组。排除标准:重复或类似的同一研究、综述文献(或个案报道等)。资料提炼:共收集到79篇有关选择素研究方面的文章,33个实验或临床研究符合纳入标准。排除的46篇文献中,32篇为未随机研究或重复性研究,14篇为综述类文章。资料综合:33个实验包括403例患者和342只实验动物,分别阐述了以下3点:①选择素家族的组成、分布:目前发现的选择素家族包括3个成员:L-选择素、P-选择素、E-选择素,P-选择素和E-选择素表达于内皮细胞,L-选择素只表达于白细胞。②选择素的结构及其表达:选择素分子是一类Ⅰ型跨膜糖蛋白,它分为胞外区、跨膜区和胞内区,3种选择素的胞外区的不同部位在同一物种或不同物种间有一定的同源性。而跨膜区和胞内区则没有同源性,胞内区是细胞内部分。③选择素的配体:选择素执行其功能离不开和其配体的相互作用,配体包括糖类配体和蛋白类配体两部分。糖类配体主要是一些寡糖基团。蛋白类配体多是一些分子量在数万到数十万单位的蛋白分子。④选择素的主要功能为:介导炎症过程中白细胞的起始黏附,参与肿瘤转移过程,参与缺血-再灌注损伤,参与血栓形成及促进创伤的修复和愈合,参与细胞内外的信号传递,参与器官移植免疫排斥反应等。结论:①目前发现的选择素家族的3个成员,P-选择素和E-选择素表达于内皮细胞,L-选择素只表达于白细胞。②选择素的主要作用是在炎症发生时介导白细胞与血管内皮细胞的起始黏附,以及介导白细胞之间、白细胞与血小板之间的黏附。此外,在淋巴细胞归巢、炎症反应、血栓形成、自身免疫性疾病及肿瘤转移等过程中,选择素还发挥着重要作用。     

Human immunodeficiency virus seroprevalence among blood product recipients in San Francisco before transfusion

To determine the incidence of transfusion-associated human immunodeficiency virus (HIV) infection after routine screening of donated blood, a pilot study estimated the pretransfusion prevalence of HIV infection among blood product recipients in San Francisco. Among the 911 nonduplicate pretransfusion specimens from recipients without a clinical history of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC), the overall prevalence of antibody to HIV was 2.9 percent (5.2% among males and 0.6% among females; p = 0.00002). If recipients in specifically defined or possible high-risk groups (n = 348) were excluded, a seropositivity rate of 1.8 percent (10/563) was detected, with all the positives occurring in men (10/242, 4.1%) and none in women (0/321, 0%). This demonstrated prevalence of HIV infection among blood product recipients in San Francisco before transfusion was substantially higher than the known 0.02 to 0.04 percent prevalence in the donor population. Therefore, the population of women without known risk for AIDS is the best in which to assess the risk of HIV infection in patients who are currently receiving seronegative blood transfusions.     

傣药小灯台中的吲哚生物碱

从傣药小灯台(Winchia catophylla A. DC.)中分到4个吲哚生物碱,经理化常数测定,光谱分析和化学转化,分别鉴定为echitamine chloride(Ⅰ),echitamidine(Ⅱ),N_B-demethyl-echitamine(Ⅲ)和22-O-acetyl-N_b--demethyl-echitamine(Ⅳ),其中Ⅳ为新的吲哚生物碱。