BACKGROUND & AIMS: :Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes. Microbial burden, or "bioburden," is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene. Comparatively, wound cultures, the standard diagnostic in the clinic, vastly underrepresent microbial load, microbial diversity, and the presence of potential pathogens. DFU microbiomes were heterogeneous, even in our tightly restricted study population, but partitioned into three clusters distinguished primarily by dominant bacteria and diversity. Ulcer depth was associated with ulcer cluster, positively correlated with abundance of anaerobic bacteria, and negatively correlated with abundance of Staphylococcus. Ulcer duration was positively correlated with bacterial diversity, species richness, and relative abundance of Proteobacteria, but was negatively correlated with relative abundance of Staphylococcus. Finally, poor glycemic control was associated with ulcer cluster, with poorest median glycemic control concentrating to Staphylococcus-rich and Streptococcus-rich ulcer clusters. Analyses of microbial community membership and structure may provide the most useful metrics in prospective studies to delineate problematic bioburden from benign colonization that can then be used to drive clinical treatment.

背景与目标： ：非愈合性糖尿病足溃疡（DFU）是糖尿病的常见且代价高昂的并发症。尽管对影响微生物负荷，多样性和/或致病性的临床因素知之甚少，但是微生物负荷或“生物负荷”被认为是延迟愈合的基础。我们使用细菌16S核糖体RNA基因的高通量测序对52例无感染临床症状的神经性非缺血性DFU的微生物群进行了分析。相比之下，伤口培养物（临床上的标准诊断方法）在很大程度上代表了微生物负荷，微生物多样性以及潜在病原体的存在。即使在我们严格限制的研究人群中，DFU微生物群也是异质的，但被分为三类，主要以优势细菌和多样性为特征。溃疡深度与溃疡簇有关，与厌氧菌的数量呈正相关，与葡萄球菌的数量呈负相关。溃疡持续时间与细菌多样性，物种丰富度和变形杆菌相对丰度呈正相关，而与葡萄球菌相对丰度呈负相关。最后，血糖控制不佳与溃疡簇有关，最差的中位血糖控制集中于富含葡萄球菌和富含链球菌的溃疡簇。在前瞻性研究中，对微生物群落组成和结构的分析可能会提供最有用的指标，以从良性定殖中确定有问题的生物负荷，然后将其用于临床治疗。

BACKGROUND & AIMS: :The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal visceral pain sensation.

背景与目标： ：内脏痛的感觉是一个复杂的过程，涉及脊髓和高级大脑结构。越来越多的证据表明肠道菌群是大脑和行为的关键调节因子，但肠道细菌是否在内脏敏感性中起作用尚待确定。我们使用无菌小鼠（GF）评估内脏敏感性，脊髓基因表达和与疼痛相关的脑结构。 GF小鼠表现出内脏超敏反应，并伴随着脊髓Toll样受体和细胞因子基因表达的增加，这可以通过用常规定殖的（CC）菌群在出生后定植来实现。在GF小鼠中，前扣带回皮质（ACC）和导水管周围灰色的体积（参与疼痛处理的区域）分别减小和增大，并且ACC中的树突状变化是明显的。这些发现表明，肠道菌群是正常内脏痛感所必需的。

BACKGROUND & AIMS: :The feasibility of using a subcutaneously implanted portal system attached to a conventional 16-gauge epidural catheter has been evaluated in 50 patients with sever pain associated with cancer. This technique allowed for the percutaneous epidural administration of morphine at 8-12-hourly intervals for pain control. The mean duration of implantation was 12 weeks and the longest period a portal remained in situ was 36 weeks. Five portals had to be removed for various reasons. The injection system has blocked on eight occasions due to catheter blockage (six times) and portal blockage (two occasions). These patients have continued to obtain excellent analgesia when either catheter or portal were replaced. In a cadaver, 300 injections were simulated using either 22-gauge Huber point needles or disposable needles (25 gauge) and the injectate examined by both light and scanning electron microscopy. Both needle types resulted in particulate contamination which was greater with the recommended Huber point needles.

背景与目标： ：已对50例与癌症相关的严重疼痛的患者评估了使用皮下植入的门禁系统连接传统的16号硬膜外导管的可行性。该技术允许以8-12小时的间隔经皮硬膜外给予吗啡以控制疼痛。平均植入时间为12周，而门户留在原位的最长时间为36周。由于各种原因，必须删除五个门户。由于导管阻塞（六次）和门静脉阻塞（两次），注射系统已发生八次阻塞。当更换导管或门静脉时，这些患者继续获得出色的镇痛效果。在尸体中，使用22号Huber点针或一次性针头（25号针头）模拟了300次注射，并通过光学和扫描电子显微镜对注射进行了检查。两种类型的针都导致微粒污染，建议的Huber点式针污染更大。

BACKGROUND & AIMS: :Neuropathic pain is a result of complex interactions between peripheral and central mechanisms with multiple potential therapeutic targets. However, the complexity of these mechanisms and relative youth of translational pain research, which is in its infancy, have prevented translation of successful basic bench research to human therapy. Most of the clinically available neuropathic pain treatments are borrowed from other therapeutic areas, such as antidepressants and antiepileptics, or involve application of older therapy, such as opioids. Exceptions are ziconotide, tapentadol, and the high-concentration capsaicin patch. Similar to all other analgesic agents, these provide only partial pain relief in subsets of patients. The standard of care for patients with chronic neuropathic pain is multimodal and multidisciplinary. For most patients to achieve and maintain satisfactory pain relief a combination of therapeutic agents is necessary, providing the empiric basis for rational polypharmacy, which has become a standard approach as well.

背景与目标： ：神经性疼痛是外周和中枢机制与多个潜在治疗靶点之间复杂相互作用的结果。但是，这些机制的复杂性以及相对较年轻的转化性疼痛研究尚处于起步阶段，因此阻碍了成功的基础实验研究向人类疗法的转化。大多数临床上可用的神经性疼痛疗法是从其他治疗领域（如抗抑郁药和抗癫痫药）借来的，或涉及使用较老的疗法（如阿片类药物）。齐考诺肽，他喷他多和高浓度辣椒素贴剂除外。与所有其他止痛药类似，这些止痛药仅能部分缓解部分患者的疼痛。慢性神经性疼痛患者的护理标准是多模式和多学科的。对于大多数患者来说，要达到并维持令人满意的止痛效果，必须结合治疗药物，为合理的多药治疗提供经验基础，这也已成为一种标准方法。

BACKGROUND & AIMS: OBJECTIVE:Anticipated pain with intrauterine device (IUD) insertion may be a barrier to widespread use. Our objective was to evaluate the efficacy of intracervical 2% lidocaine gel for pain relief with IUD insertion. STUDY DESIGN:We performed a double-blind, randomized controlled trial of women undergoing IUD insertion. Participants were randomly assigned to 2% lidocaine or placebo gel. Study gel (3 mL) was placed 3 minutes prior to IUD insertion. Pain scores were measured at various time points using a 10-point visual analog scale. RESULTS:Of the 200 participants randomized, 199 completed the study. Pain scores among lidocaine and placebo arms were similar at tenaculum placement (lidocaine and placebo: median, 4; range, 0-10; P = .15) and with insertion (lidocaine: median, 5; range, 1-10; placebo: median, 6; range, 0-10; P = .16). These results did not differ by parity. CONCLUSION:Topical or intracervical 2% lidocaine gel prior to IUD insertion does not decrease pain scores.

背景与目标： 目的：宫内节育器（IUD）插入会导致预期的疼痛可能是广泛使用的障碍。我们的目标是评估2％利多卡因腹腔内凝胶治疗宫内节育器疼痛缓解的效果。
研究设计：我们对接受宫内节育器植入的妇女进行了一项双盲，随机对照试验。参与者被随机分配到2％利多卡因或安慰剂凝胶中。在插入宫内节育器之前3分钟放置研究凝胶（3 mL）。使用10点视觉模拟量表在各个时间点测量疼痛评分。
结果：在随机分配的200名参与者中，有199名完成了研究。利多卡因和安慰剂组之间的疼痛评分在触角放置（利多卡因和安慰剂：中位数，4；范围，0-10； P = .15）和插入时相似（利多卡因：中位数，5；范围，1-10；安慰剂：中位数为6；范围为0-10； P = 0.16）。这些结果在均等方面没有差异。
结论：在宫内节育器插入前局部或颅内使用2％利多卡因凝胶不会降低疼痛评分。

BACKGROUND & AIMS: BACKGROUND:Many brain areas participate to supraspinal control of nociception. In these regions, few studies have investigated the role of glial cells in supraspinal plasticity and the effect of 7-day intrathecal nerve growth factor-like (BB14®, Blueprint Biotech, Milano, Italy) treatment. METHODS:In male Sprague-Dawley rats, we evaluated by immunohistochemistry the morphological and molecular rearrangement of neuroglial network occurring in several supraspinal brain regions involved in pain processing following spared nerve injury (SNI) of the sciatic nerve. In particular, the medial prefrontal cortex, the amygdala (Amy), the nucleus accumbens (Acb), the thalamus and the periaqueductal gray were analysed. RESULTS:Despite the modifications occurring in the dorsal horn of spinal cord following SNI, no significant changes in the Iba1 and glial fibrillary acidic protein (GFAP) expression were detected in all the analysed supraspinal regions, except for the Amy, showing a remarkable GFAP increase. Interestingly, neuropathic rats also displayed a significant increase of glial transporters (GTs) in all the supraspinal regions. Finally, the analysis of vesicular glutamate transporter 1 (vGLUT1) and vesicular gamma-aminobutyric acid (GABA) transporter (vGAT) expression revealed a significant enhancement of glutamatergic/GABAergic ratio in all selected brain regions of SNI animals, except for Acb. Both glial activation in the Amy and alteration of GTs and vGLUT/vGAT levels observed in neuropathic animals were largely reversed by BB14® treatment. CONCLUSIONS:All together, these data strengthen the role of supraspinal neuroglial network plasticity in the establishment of neuropathic pain syndrome. The hallmark is represented by the divergence between glial reaction confined to Amy and the widespread changes in the GT distribution and glutamate/GABA ratio detected in the other supraspinal region.

背景与目标： 背景：许多大脑区域参与了脊髓上的伤害感受控制。在这些地区，很少有研究调查神经胶质细胞在棘上棘可塑性中的作用以及7天鞘内神经生长因子样治疗的作用（BB14®，Blueprint Biotech，米兰，意大利）。
方法：在雄性Sprague-Dawley大鼠中，我们通过免疫组织化学方法评估了坐骨神经备用神经损伤（SNI）后参与疼痛处理的多个棘上大脑区域中神经胶质网络的形态和分子重排。特别地，分析了内侧前额叶皮层，杏仁核（Amy），伏隔核（Acb），丘脑和导水管周围的灰色。
结果：尽管SNI后脊髓背角发生了改变，但除Amy外，在所有分析的脊髓上上区均未检测到Iba1和神经胶质纤维酸性蛋白（GFAP）表达的显着变化，显示GFAP显着增加。有趣的是，神经病变大鼠在所有棘上神经区也显示出神经胶质转运蛋白（GTs）的显着增加。最后，对囊泡谷氨酸转运蛋白1（vGLUT1）和囊泡γ-氨基丁酸（GABA）转运蛋白（vGAT）表达的分析显示，除Acb外，SNI动物所有选定大脑区域的谷氨酸能/ GABA能比均显着提高。在神经病动物中观察到的Amy中的神经胶质激活以及GTs和vGLUT / vGAT水平的改变都可以通过BB14®治疗大幅度逆转。
结论：这些数据加在一起增强了脊髓上神经胶质网络可塑性在建立神经性疼痛综合征中的作用。具有标志性的特征是仅限于Amy的神经胶质反应与在其他上棘突区域中检测到的GT分布和谷氨酸/ GABA比的广泛变化之间存在差异。

BACKGROUND & AIMS: OBJECTIVE:Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross-sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA). METHODS:One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs). RESULTS:After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = -0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient -10.9 [95% CI -19.5, -2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient -16.8 [95% CI -28.9, -4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]). CONCLUSION:In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement.

背景与目标： 目的：尽管有证据表明增加股四头肌力量对膝关节症状有有益作用，但对膝关节结构的影响尚不清楚。我们进行了这项研究，以检查有症状膝骨关节炎（OA）患者的股内侧截面积（CSA）变化与膝关节疼痛，胫骨软骨体积和膝关节置换风险之间的关系。
方法：117名有症状膝骨关节炎的受试者在基线，2岁和4.5岁接受了膝部磁共振成像。在基线和第2年测量中侧股静脉CSA。在基线以及第2和4.5年测量胫骨软骨体积。在基线和第2年，通过西安大略和麦克马斯特大学的骨关节炎指数评估膝关节疼痛。确定了4年内膝关节置换的频率。确定回归系数（B）和比值比以及95％的置信区间（95％CI）。
结果：校正混杂因素后，基线膝关节内侧CSA与当前膝关节疼痛呈负相关（r = -0.16，P = 0.04），并且与基线至2年时胫骨软骨内侧体积损失呈负相关（B系数-10.9 [95％CI- 19.5，-2.3]），但不包括胫骨基线软骨体积。此外，从基线期到2年内，腓肠肌CSA的增加与同期膝关节疼痛的减轻有关（r = 0.24，P = 0.007），胫骨内侧软骨损失从2年减少到4.5年（B系数-16.8） [95％CI -28.9，-4.6]），并在4年内降低了膝关节置换的风险（赔率0.61 [95％CI 0.40，0.94]）。
结论：在有症状的膝骨关节炎患者中，股骨内侧vast增大与膝关节疼痛减轻和膝部有益的结构变化有关，这表明管理膝痛和优化股骨内侧media肌对于减少OA进展和随后的膝关节起重要作用。替代品。

BACKGROUND & AIMS: :Previous surveys showed a poor quality of the web sites providing health information about low back pain. However, the rapid and continuous evolution of the Internet content may question the current validity of those investigations. The present study is aimed to quantitatively assess the quality of the Internet information about low back pain retrieved with the most commonly employed search engines. An Internet search with the keywords "low back pain" has been performed with Google, Yahoo!® and Bing™ in the English language. The top 30 hits obtained with each search engine were evaluated by five independent raters and averaged following criteria derived from previous works. All search results were categorized as declaring compliant to a quality standard for health information (e.g. HONCode) or not and based on the web site type (Institutional, Free informative, Commercial, News, Social Network, Unknown). The quality of the hits retrieved by the three search engines was extremely similar. The web sites had a clear purpose, were easy to navigate, and mostly lacked in validity and quality of the provided links. The conformity to a quality standard was correlated with a marked greater quality of the web sites in all respects. Institutional web sites had the best validity and ease of use. Free informative web sites had good quality but a markedly lower validity compared to Institutional websites. Commercial web sites provided more biased information. News web sites were well designed and easy to use, but lacked in validity. The average quality of the hits retrieved by the most commonly employed search engines could be defined as satisfactory and favorably comparable with previous investigations. Awareness of the user about checking the quality of the information remains of concern.

背景与目标： ：以前的调查显示，提供有关下腰痛的健康信息的网站质量很差。但是，Internet内容的快速和持续发展可能会质疑这些调查的当前有效性。本研究旨在定量评估使用最常用的搜索引擎检索到的有关腰痛的Internet信息的质量。 Google，Yahoo！®和Bing™已使用英语进行了关键字为“腰痛”的Internet搜索。每个搜索引擎获得的前30个匹配均由5个独立的评分者进行了评估，并根据从先前工作得出的标准进行了平均。根据网站类型（机构，免费，商业，新闻，社交网络，未知），所有搜索结果均归类为声明是否符合卫生信息质量标准（例如HONCode）。三个搜索引擎检索到的匹配的质量非常相似。该网站的目的明确，易于浏览，并且大多缺乏所提供链接的有效性和质量。在各个方面，对质量标准的符合与网站质量的显着提高相关。机构网站具有最佳的有效性和易用性。与机构网站相比，免费的信息网站质量好，但有效性明显较低。商业网站提供了更多有偏见的信息。新闻网站设计合理，易于使用，但缺乏有效性。由最常用的搜索引擎检索到的匹配的平均质量可以定义为令人满意，并且可以与以前的调查相媲美。用户关于检查信息质量的意识仍然值得关注。

BACKGROUND & AIMS: :To evaluate the effectiveness of intravenous clodronate in ameliorating refractory bone pain in patients with metastatic bone disease, 60 patients with established osseous metastases and persistent bone pain were randomized to receive either clodronate (600 mg or 1500 mg in 500 mL of normal saline) or 500 mL of saline as placebo. After 2 weeks, the patients were crossed over to receive the alternate treatment. After another 2 weeks, each patient and investigator made a blinded choice. Daily visual analogue scales (VAS) and analgesic diaries were recorded throughout the study period. Forty-six patients were evaluable (77%). A treatment x period interaction was identified in the VAS and daily morphine equivalent dose (DMED) scores. First period analysis of the VAS scores for general pain, pain at rest, and pain upon movement demonstrated an average reduction of 13, 14, and 24 mm, respectively, from baseline, but were not significantly different from changes following placebo. The average change in DMED was -6.4 (SE = 2.9) following clodronate and was +24.6 (SE = 14.9) following placebo (p = 0.03). In the blinded choice of which agent resulted in improvement in pain, 26 (57%) patients chose clodronate, 12 (26%) chose placebo, and eight (17%) had no preference (p = 0.0021). For the investigators who also made a blinded selection, clodronate was chosen in 30 (65%) patients, placebo in ten (22%) patients, and no difference was apparent in six (13%) (p < 0.0001). Intravenous clodronate appeared to have analgesic effect in patients with refractory bone pain due to metastatic bone disease. The optimal dose and duration of effect require further evaluation, particularly in patients with stable disease and persistent bone pain.

背景与目标： ：为评估静脉注射氯膦酸盐缓解转移性骨病患者难治性骨痛的有效性，随机将60例骨转移明确且持续性骨痛的患者随机接受氯膦酸盐（600毫克或1500毫克于500毫升生理盐水中）或500 mL生理盐水作为安慰剂。 2周后，将患者交叉接受替代治疗。再过2周后，每个患者和研究者都做出了盲目的选择。在整个研究期间记录每日视觉模拟量表（VAS）和止痛日记。 46名患者可评估（77％）。在VAS和每日吗啡当量剂量（DMED）评分中确定了治疗x周期相互作用。对一般性疼痛，静止性疼痛和运动性疼痛的VAS评分的第一阶段分析显示，与基线相比平均减少了13 mm，14 mm和24 mm，但与安慰剂治疗后的变化无显着差异。氯膦酸盐治疗后DMED的平均变化为-6.4（SE = 2.9），安慰剂治疗后为24.6（SE = 14.9）（p = 0.03）。在对导致疼痛改善的药剂的盲目选择中，有26名（57％）患者选择了氯膦酸盐，12名（26％）患者选择了安慰剂，而八名（17％）患者没有偏爱（p = 0.0021）。对于同样做盲法选择的研究者，在30名（65％）患者中选择了氯膦酸盐，在十名（22％）患者中选择了安慰剂，在六名（13％）中没有发现明显的差异（p <0.0001）。在由于转移性骨病导致的难治性骨痛患者中，静脉注射氯膦酸盐似乎具有镇痛作用。最佳剂量和效果持续时间需要进一步评估，尤其是在疾病稳定且持续存在骨痛的患者中。

BACKGROUND & AIMS: :Opioid rotation is increasingly becoming an option to improve pain management especially in long-term treatment. Because of insufficient analgesia and intolerable side effects, a total of 42 patients (23 male, 19 female; mean age 64.1 years) suffering from severe musculoskeletal (64%), cancer (21%) or neuropathic (19%) pain were converted from high-dose morphine (120 to >240 mg/day) to transdermal buprenorphine. The dose of buprenorphine necessary for conversion (at least 52.5 microg/h) was titrated individually by the treating physician. No conversion recommendations were given and the treating physician used his or her own judgment for dose adjustment. Pain relief, overall satisfaction and quality of sleep (very good, good, satisfactory, poor, or very poor), and the incidence and severity of adverse drug reactions over a period of at least 10 weeks and up to 1 year was assessed. Following rotation, patients experiencing good/very good pain relief increased from 5% to 76% (P < 0.001). Only 5% reported insufficient relief. Relief was achieved with buprenorphine alone in 77.4%, while 17% needed an additional opioid for breakthrough pain. Sleep quality (good/very good) increased from 14% to 74% (P < 0.005). Adverse effects were reported in 11.9%, mostly because of local irritation, did not result in termination of therapy. Neither tolerance nor refractory effect following rotation from morphine to buprenorphine was noted. Conversion tables with a fixed conversion ratio are of limited value in patients treated with high-dose morphine.

背景与目标： ：阿片类药物的旋转越来越成为改善疼痛管理的一种选择，尤其是在长期治疗中。由于镇痛作用不足和副作用难以忍受，总共有42例重度骨骼肌（64％），癌症（21％）或神经性（19％）疼痛的患者（男23例，女19例；平均年龄64.1岁）从高剂量吗啡（120至> 240毫克/天）至透皮丁丙诺啡。由治疗医师单独滴定转化所需的丁丙诺啡剂量（至少52.5 microg / h）。没有给出转换建议，主治医生使用他或她自己的判断来调整剂量。评估疼痛缓解，总体满意度和睡眠质量（非常好，良好，满意，差或非常差），以及至少10周至1年的药物不良反应的发生率和严重程度。旋转后，经历良好/非常良好的疼痛缓解的患者从5％增加到76％（P <0.001）。只有5％的人表示救济不足。仅丁丙诺啡的缓解率为77.4％，而17％的患者需要额外的阿片类药物来缓解疼痛。睡眠质量（好/非常好）从14％提高到74％（P <0.005）。据报道有11.9％的不良反应，主要是由于局部刺激，并未导致治疗终止。从吗啡转为丁丙诺啡后，没有耐受性或难治性作用。在使用大剂量吗啡治疗的患者中，固定转换率的转换表价值有限。

BACKGROUND & AIMS: :The complex problem of combined neck and shoulder pain was investigated in 26 operations in 13 patients who had a shoulder procedure (subacromial decompressions or rotator cuff repairs) and an anterior cervical spine fusion. This select group of complex patients illustrates the diagnostic studies required to determine whether the pain comes primarily from the cervical spine, shoulder, or both. Good pain relief was accomplished after 24 of the 26 surgical procedures (average follow-up, 4.3 years). In the 13 patients, eight presented with nearly equal neck and shoulder pain as the chief complaint, whereas in the remaining five patients, the initial complaint was predominantly neck pain with only minor shoulder involvement. The shoulder pain became more significant after the anterior cervical fusion in these five patients. This study emphasizes the need for a careful evaluation of patients with combined neck-shoulder pain syndrome in a systematic approach allowing appropriate treatment.

背景与目标： ：对13例肩关节手术（肩峰以下减压或肩袖修复）和颈椎前路融合术的患者进行了26例手术，研究了颈肩关节疼痛的复杂问题。这组复杂的患者阐明了确定疼痛是否主要来自颈椎，肩部或两者的疼痛所需的诊断研究。在26项外科手术中的24项（平均随访时间为4.3年）后，疼痛得到了很好的缓解。在13例患者中，有8例主要主诉为颈部和肩部疼痛，而其余5例中，最初的主诉主要为颈部疼痛，仅有轻微的肩部受累。在这五例患者中，颈椎前路融合术后肩痛变得更加明显。这项研究强调需要以系统的方法对合并的肩-肩痛综合症患者进行仔细评估，以进行适当的治疗。

BACKGROUND & AIMS: BACKGROUND:Shoulder tip and abdominal pain following laparoscopic procedures are well recognized causes of postoperative morbidity. In this double-blind randomized clinical trial attempts were made to reduce postoperative pain in patients undergoing laparoscopic surgery by implementing a simple intraoperative technique. METHODS:Patients undergoing elective laparoscopic cholecystectomy or laparoscopic transabdominal preperitoneal inguinal hernia repair were randomized to receive either the current standard treatment (control group) or an intervention to remove residual carbon dioxide. In the intervention group, the pneumoperitoneum was removed at the end of the operation by placing the patient in the Trendelenburg position and utilizing a pulmonary recruitment manoeuvre consisting of two manual inflations to a maximum pressure of 60 cmH2 O. In the control group, residual pneumoperitoneum was evacuated at the end of the procedure by passive decompression via the open operative ports. RESULTS:Seventy-six randomly assigned patients, 37 in the intervention group and 39 in the control group, were recruited. Overall postoperative pain scores were significantly lower in the intervention group (P = 0·001). Median (interquartile range) pain scores were significantly lower in the intervention group compared with the control group at both 12 h (3·5 versus 5; P < 0·010) and 24 h (3 versus 4·5; P < 0·010). CONCLUSION:Active evacuation of residual pneumoperitoneum following laparoscopic procedures, by means of two pulmonary recruitment manoeuvres in the Trendelenburg position, reduces postoperative pain significantly. This simple and safe technique can be implemented routinely after abdominal laparoscopy. REGISTRATION NUMBER:NCT01720433 (http://www.clinical trials.gov).

背景与目标： 背景：腹腔镜手术后的肩尖和腹部疼痛是公认的术后发病原因。在这项双盲随机临床试验中，尝试通过实施简单的术中技术来减轻接受腹腔镜手术的患者的术后疼痛。
方法：将接受选择性腹腔镜胆囊切除术或腹腔镜经腹腔腹膜前腹股沟疝修补术的患者随机接受当前标准治疗（对照组）或采取干预措施以清除残留的二氧化碳。在干预组中，在手术结束时通过将患者置于特伦德伦伯卧位并利用由两次手动充气组成的最大压力为60 cmH2 O的肺募集动作来切除气腹。在对照组中，残留气腹在手术结束时，通过开放的手术口进行被动减压，将患者撤离。
结果：随机招募了76例患者，干预组37例，对照组39例。干预组的总体术后疼痛评分显着降低（P = 0·001）。干预组在12 h（3·5 vs 5; P <0·010）和24 h（3 vs 4·5; P <0· 010）。
结论：腹腔镜手术后，通过在特伦德伦伯卧位进行两次肺部募集活动，积极清除残留的气腹，可显着减轻术后疼痛。这种简单安全的技术可以在腹腔镜检查后常规实施。
注册号：NCT01720433（http：//www.clinical trial.gov）。

BACKGROUND & AIMS: BACKGROUND:Modic changes (MC) are associated with low back pain (LBP). In this study, we compared changes in size and type of MC, after a single intravenous infusion of 5 mg zoledronic acid (ZA) or placebo, among chronic LBP patients with MC on magnetic resonance imaging (MRI), and evaluated whether the MRI changes correlate with symptoms. METHODS:All patients (N = 19 in ZA, 20 in placebo) had MRI at baseline (0.23-1.5 T) and at one year (1.5-3 T). We evaluated the level, type and volume of all the MC. The MC were classified into M1 (M1 (100%)), predominating M1 (M1/2 (65:35%)) or predominating M2 (M1/2 (35:65%)), and M2 (M2 (100%)). The first two were considered M1-dominant, and the latter two M2-dominant. Volumes of M1 and M2 were calculated separately for the primary MC, which was assumed to cause the symptoms, and the other MC. We analysed the one-year treatment differences in M1 and M2 volumes using analysis of covariance with adjustments for age, sex, body mass index, and smoking. The correlations between the MRI changes and the changes in LBP symptoms were analysed using Pearson correlations. RESULTS:In the ZA group, 84.2% of patients had M1-dominant primary MC at baseline, compared to 50% in the placebo group (p = 0.041). The primary MC in the ZA group converted more likely to M2-dominant (42.1% ZA, 15% placebo; p = 0.0119). The other MC (15 ZA, 8 placebo) were on average 42% smaller and remained largely M2-dominant. The M1 volume of the primary MC decreased in the ZA group, but increased in the placebo group (-0.83 cm3 vs 0.91 cm3; p = 0.21). The adjusted treatment difference for M1 volume was -1.9 cm3 (95% CI -5.0 to 1.2; p = 0.22) and for M2 volume 0.23 cm3 (p = 0.86). In the MC that remained M1-dominant, volume change correlated positively with increased symptoms in the placebo group, whereas the correlations were negative and weak in the ZA group. CONCLUSIONS:Zoledronic acid tended to speed up the conversion of M1-dominant into M2-dominant MC and decrease the volume of M1-dominant MC, although statistical significance was not demonstrated. TRIAL REGISTRATION:The registration number in ClinicalTrials.gov is NCT01330238 and the date of registration February 11, 2011.

背景与目标： 背景：Modic change（MC）与下背痛（LBP）相关。在这项研究中，我们比较了在接受磁共振成像（MRI）的MC的慢性LBP患者中，单次静脉注射5 mg唑来膦酸（ZA）或安慰剂后MC的大小和类型的变化，并评估了MRI是否改变与症状相关。
方法：所有患者（ZA中N = 19，安慰剂中20）在基线（0.23-1.5 T）和一年（1.5-3 T）均接受MRI检查。我们评估了所有MC的级别，类型和体积。 MC分为M1（M1（100％）），M1（M1 / 2（65：35％））或M2（M1 / 2（35：65％））以及M2（M2（100％） ）。前两个被认为是M1主导，后两个被认为是M2主导。 M1和M2的体积分别针对假定会引起症状的主MC和其他MC进行计算。我们使用年龄，性别，体重指数和吸烟调整的协方差分析，分析了M1和M2量在一年治疗中的差异。使用Pearson相关性分析MRI变化与LBP症状变化之间的相关性。
结果：在ZA组中，有84.2％的患者在基线时具有M1为主的原发性MC，而在安慰剂组中则为50％（p = 0.041）。 ZA组中的主要MC更有可能转化为M2型（42.1％ZA，15％安慰剂; p = 0.0119）。另一个MC（15 ZA，8个安慰剂）平均缩小了42％，并且仍以M2为主。在ZA组中，主要MC的M1体积减少，但在安慰剂组中增加（-0.83 cm3对0.91 cm3; p = 0.21）。 M1体积的调整后治疗差异为-1.9 cm3（95％CI -5.0至1.2; p = 0.22），M2体积为0.23 cm3（p = 0.86）。在以M1为主的MC中，安慰剂组的体量变化与症状增加呈正相关，而ZA组的相关性为负而微弱。
结论：唑来膦酸具有加速M1主导型向M2主导型MC转化的作用，并降低M1主导型MC的体积，尽管没有统计学意义。
试用注册：ClinicalTrials.gov中的注册号为NCT01330238，注册日期为2011年2月11日。

BACKGROUND & AIMS: BACKGROUND:In the past, the efficacy of local infiltration of liposomal bupivacaine for total hip arthroplasty (THA) patients was in debate. Therefore, this meta-analysis was conducted to determine whether local infiltration of liposomal bupivacaine provides better pain relief after THA. METHODS:We searched Web of Science, PubMed, Embase, and the Cochrane Library databases to the April 2017. Any studies comparing liposomal bupivacaine and traditional bupivacaine were included in our meta-analysis. The outcomes included visual analog scale (VAS) at 24, 48, and 72 hours, total morphine consumption at 24 hours, and the length of hospital stay. We assessed the pooled data using a random-effect model. RESULTS:Six studies were finally included in this meta-analysis. Our pooled data analysis demonstrated that liposomal bupivacaine was more effective than the traditional bupivacaine in terms of VAS at 24 hours (P  =  .018) and the length of hospital stay (P  =  .000). There was no significant difference in terms of the VAS at 48 and 72 hours and total morphine consumption at 24 hours (P >.05). CONCLUSION:Compared with the traditional bupivacaine, liposomal bupivacaine shows better pain control at 24 hours and reduces the length of hospital stay after THA. Its economic costs must be assessed in multimodal center randomized controlled trials when being recommended as a long-acting alternative analgesic agent for a THA patient.

背景与目标： 背景：过去，脂质体布比卡因局部浸润对全髋关节置换术（THA）患者的疗效一直存在争议。因此，进行了这项荟萃分析，以确定脂质体布比卡因的局部浸润是否可以在THA后更好地缓解疼痛。
方法：我们搜索了Web of Science，PubMed，Embase和Cochrane图书馆数据库，直至2017年4月。我们对荟萃分析中所有比较脂质体布比卡因和传统布比卡因的研究都包括在内。结果包括24、48和72小时时的视觉模拟量表（VAS），24小时时的总吗啡消耗量以及住院时间。我们使用随机效应模型评估了汇总数据。
结果：该荟萃分析最终包括六项研究。我们的汇总数据分析表明，脂质体布比卡因在24小时时的VAS（P than = .018）和住院时间（P = .000）方面比传统布比卡因更有效。在48和72小时时的VAS和24小时时的总吗啡消耗量方面无显着差异（P> .05）。
结论：与传统布比卡因相比，脂质体布比卡因在24小时可更好地控制疼痛，并缩短THA后的住院时间。当被推荐作为THA患者的长效替代镇痛药时，必须在多模式中心随机对照试验中评估其经济成本。

BACKGROUND & AIMS: :Application of functional imaging techniques to animal models is vital to understand pain mechanisms, but is often confounded by the need to limit movement artefacts with anaesthesia, and a focus on evoked responses rather than clinically relevant spontaneous pain and related hyperalgesia. The aim of the present study was to investigate the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to measure neural responses during on-going pain that underpins hyperalgesia in pre-clinical models of nociception. As a proof of concept that MEMRI is sensitive to the neural activity of spontaneous, intermittent behaviour, we studied a separate positive control group undergoing a voluntary running wheel experiment. In the pain models, pain behaviour (weight bearing asymmetry and hindpaw withdrawal thresholds (PWTs)) was measured at baseline and following either intra-articular injection of nerve growth factor (NGF, 10µg/50µl; acute pain model, n=4 rats per group), or the chondrocyte toxin monosodium iodoacetate (MIA, 1mg/50µl; chronic model, n=8 rats per group), or control injection. Separate groups of rats underwent a voluntary wheel running protocol (n=8 rats per group). Rats were administered with paramagnetic ion Mn2+ as soluble MnCl2 over seven days (subcutaneous osmotic pump) to allow cumulative activity-dependent neural accumulation in the models of pain, or over a period of running. T1-weighted MR imaging at 7T was performed under isoflurane anaesthesia using a receive-only rat head coil in combination with a 72mm volume coil for excitation. The pain models resulted in weight bearing asymmetry (NGF: 20.0 ± 5.2%, MIA: 15 ± 3%), and a reduction in PWT in the MIA model (8.3 ± 1.5g) on the final day of assessment before undergoing MR imaging. Voxel-wise and region-based analysis of MEMRI data did not identify group differences in T1 signal. However, MnCl2 accumulation in the VTA, right Ce amygdala, and left cingulate was negatively correlated with pain responses (greater differences in weight bearing), similarly MnCl2 accumulation was reduced in the VTA in line with hyperalgesia (lower PWTs), which suggests reduced regional activation as a result of the intensity and duration of pain experienced during the 7 days of MnCl2 exposure. Motor cortex T1-weighted signal increase was associated with the distance ran in the wheel running study, while no between group difference was seen. Our data suggest that on-going pain related signal changes identified using MEMRI offers a new window to study the neural underpinnings of spontaneous pain in rats.

背景与目标： ：功能成像技术在动物模型中的应用对于理解疼痛机制至关重要，但通常因需要限制运动伪影并进行麻醉，并且侧重于诱发反应而不是临床相关的自发性疼痛和相关的痛觉过敏而感到困惑。本研究的目的是研究锰增强磁共振成像（MEMRI）在持续疼痛过程中测量神经痛的潜在能力，该疼痛在临床前伤害感受模型中是痛觉过敏的基础。作为MEMRI对自发性，间歇性行为的神经活动敏感的概念的证明，我们研究了一个单独的阳性对照组，他们接受了一项自愿的自转轮实验。在疼痛模型中，在基线时以及关节内注射神经生长因子（NGF，10µg / 50µl；急性疼痛模型，每只n = 4只大鼠）时，测量基线时的疼痛行为（负重不对称和后爪缩回阈值（PWTs））。组）或软骨细胞毒素碘乙酸单钠（MIA，1mg / 50µl；慢性模型，每组n = 8只大鼠）或对照注射液。单独的大鼠组接受自愿轮转方案（每组n = 8只大鼠）。在7天（皮下渗透泵）中，给大鼠施用了顺磁性离子Mn2作为可溶的MnCl2，以允许在疼痛模型中或在一段时间内累积依赖于活动的神经蓄积。在异氟烷麻醉下，使用仅接收的大鼠头部线圈和72mm体积线圈进行激励，在异氟烷麻醉下进行7T的T1加权MR成像。疼痛模型导致负重不对称（NGF：20.0±5.2％，MIA：15±3％），并且在进行MR成像前的评估的最后一天，MIA模型中的PWT减少（8.3±1.5g）。 MEMRI数据的基于体素分析和基于区域的分析未发现T1信号中的组差异。然而，VTA，右Cy杏仁核和左扣带中的MnCl2积累与疼痛反应呈负相关（负重差异更大），与痛觉过敏一致，VTA中的MnCl2积累减少（PWT较低），这表明区域性减少MnCl2暴露7天期间疼痛的强度和持续时间的结果是激活。运动皮层T1加权信号的增加与车轮行驶研究中的跑步距离相关，而两组之间未见差异。我们的数据表明，使用MEMRI识别的与疼痛相关的持续信号变化为研究大鼠自发性疼痛的神经基础提供了新的窗口。