BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌症疼痛患者中吗啡连续静脉输注（CIVI）与吗啡连续皮下输注（CSCI）的剂量，疗效和副作用。符合条件的患者被转到姑息治疗计划，并接受稳定剂量的吗啡CIVI。该设计是患者内部的单向交叉。其中每个患者提供了从吗啡从CIVI切换到CSCI之前和之后的数据。 “救援”剂量是根据需要每2小时给予的每小时剂量的50％。吗啡通过McGaw / AccuPro容量输注泵静脉内（i.v.）和皮下（s.c.）输注。获得包括副作用和疼痛评估在内的基线数据后，每天对患者进行两次毒性和止痛效果评估。连续48个小时具有稳定CIVI剂量的患者以与静脉内（i.v.）阶段相同的剂量转入CSCI。稳定剂量定义为无剂量变化，在过去24小时内有四个或更少的急救剂量，疼痛等级为无或轻度。如果连续96个小时保持这些标准，则认为CIVI等于CSCI。入组患者57例，其中40例可评估（女性15例，男性25例）。中位年龄为67岁（范围为30-83岁）。在整个静脉内维持稳定剂量后，所有40位参与者阶段，跨到南卡罗来纳州相并保持在s.c.至少持续48小时。在整个静脉内，有32名患者维持了稳定的剂量。和s.c.阶段。平均稳定i.v.剂量（第2天）为5.05 mg / hr，平均稳定s.c.剂量（第4天）为5.7 mg / hr（P = 0.01）。第2天的平均急救剂量为每24小时0.83，而第4天为每24小时0.80（P = 0.6）。第2天的平均类别疼痛评分为0.83，第4天的平均疼痛评分为0.85（P = 0.7）。第2天的平均视觉模拟量表（VAS）为22.9毫米，而第4天为17.6毫米（P = 0.1）。第2天的副作用的平均发生率为1.7，而第4天的平均发生率为2.0（P = 0.2）。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点的局部毒性（轻度红斑）的报道，需要进行部位改变。我们所有的40名患者均通过CIVI和CSCI吗啡可以很好地控制疼痛。在没有保持相同i.v.的八位参与者中和s.c.剂量较高时，所有患者均具有足够的疼痛控制和较高的皮下副作用。吗啡剂量。这些数据表明和s.c.当以连续输注方式给药时，对于大多数患者而言，这两种途径均具有镇痛作用。疼痛控制和副作用状况非常相似且可以接受。南卡罗来纳州吗啡是静脉注射的绝佳替代品。需要胃肠外吗啡治疗的住院患者和门诊患者中的吗啡疼痛。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.

背景与目标： ：交感神经维持的疼痛可能由交感传入和传入的伤害性纤维之间的神经元相互作用或儿茶酚胺诱导的伤害性神经末梢的激活介导。我们在这里报告了在交感神经痛患者中，C伤害感受器的单纤维记录，在该患者中，交感神经阻滞反复消除了双腿持续的疼痛。根据它们的机械响应性和依赖于传导速度的活动性减慢，我们将8根C纤维归为机械响应性伤害感受器，将6根C纤维归类为对机械响应不敏感的伤害感受器（20脉冲在0.125时延迟时间为0.5 /-1.1与7.1 /-2.0 ms的增加）赫兹）。在强烈的内源性交感神经爆发后，几秒钟的延迟激活了两根C纤维。在将去甲肾上腺素（10微升，0.05％）注入其神经支配区域后，他们还兴奋了约3分钟。在这两种纤维中，记录了通过注射低pH溶液（磷酸盐缓冲液，pH 6.0、10微升）的长时间激活以及注射前列腺素E2后对其热响应的敏化，证明了它们的传入性质。此外，它们对机械不敏感的伤害感受器的活动依赖性减慢作用是典型的。我们得出结论，致敏的对机械不敏感的伤害感受器可以被内源性释放的儿茶酚胺激活，从而可能有助于交感神经维持性疼痛。没有发现交感传入纤维和伤害性传入纤维之间的神经元相互作用的证据。

BACKGROUND & AIMS: AIM:To research possible associations between previous exposure to specific torture techniques and prevalent pain in the head and face, back, and feet. METHODS:221 refugees, 193 males and 28 females, previously exposed to torture in their home country, were subject to a clinical interview at a rehabilitation clinic for torture victims. The interview focused on exposure to torture and somatic symptoms prevalent at examination. RESULTS:The mean number of times imprisoned was 2.3; the mean number of months imprisoned was 19.7; the mean duration from initial imprisonment to final release was 3.7 years; and the mean duration from final release to preliminary interview was 8.4 years. The most frequent physical torture method reported was beating (92.3%) and the main mental torture method was deprivation (84.6%). Pain in the head and face was found to be strongly associated with torture against head and face (OR 3.89, 95% CI 1.49-10.20) and with the cumulative number of physical torture methods exposed to. Pain in the back was associated with sexual torture (OR 2.75, 95% CI 1.07-7.12). Besides beating of the lower extremities (OR 5.98, 95% CI 2.47-14.48), the strongest predictor for pain in the feet was general abuse of the whole body (OR 5.64, 95% CI 1.93-16.45). CONCLUSION:In spite of many factors being potentially co-responsible for prevalent pain, years after the torture took place it presents itself as strongly associated with specific loci of pain, with generalized effects, and with somatizing.

背景与目标： 目的：研究先前暴露于特定的酷刑技术与头部和面部，背部和脚部普遍疼痛之间的可能联系。
方法：221名难民，193名男性和28名女性先前在其本国遭受酷刑，在康复诊所接受酷刑受害者的临床采访。访谈的重点是检查时所遭受的酷刑和躯体症状的暴露。
结果：平均入狱次数为2.3次；平均入狱数为19.7个月；从最初入狱到最终释放的平均时间为3.7年；从最终发布到初步面试的平均时间为8.4年。报告的最经常的酷刑方法是殴打（92.3％），主要的心理酷刑方法是剥夺（84.6％）。发现头部和面部疼痛与对头部和面部的酷刑密切相关（OR 3.89，95％CI 1.49-10.20）以及所遭受的物理酷刑方法的累积数量。背部疼痛与性折磨有关（OR 2.75，95％CI 1.07-7.12）。除了下肢跳动（OR 5.98，95％CI 2.47-14.48）之外，脚部疼痛的最强预测指标是全身的普遍滥用（OR 5.64，95％CI 1.93-16.45）。
结论：尽管有许多因素可能共同导致普遍的疼痛，但在发生酷刑之后数年，它仍表现为与特定的疼痛位点密切相关，具有广泛的影响和躯体化。

BACKGROUND & AIMS: :Chronic pain may result from hyperexcitability following activation of spinal NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess NMDA antagonist activity. This study explored the possibility that stable analog [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced using the chronic constriction injury model (CCI). Intrathecal injection of SHG markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly normalizing responses. These results suggest that the natural peptide histogranin may be a novel adjunct in neuropathic pain management.

背景与目标： ：慢性疼痛可能是由脊柱NMDA受体激活后的过度兴奋引起的。天然来源的哺乳动物多肽，组织颗粒蛋白，可能具有NMDA拮抗剂活性。这项研究探讨了稳定的类似物[Ser1] Histogranin（SHG）可以减轻慢性疼痛的可能性。使用慢性收缩损伤模型（CCI）诱发神经性疼痛。鞘内注射SHG明显减轻了CCI引起的痛觉过敏和异常性疼痛，使反应趋于正常。这些结果表明，天然肽组织颗粒蛋白可能是神经性疼痛治疗的新型辅助剂。

BACKGROUND & AIMS: :Peripheral neuropathic pain is a unique form of chronic pain that afflicts up to 50% of persons with AIDS. The purpose of this pilot study was to examine the effects of ice massage to reduce neuropathic pain and improve sleep quality and to determine the feasibility of a larger study. A repeated measures design was used. The three treatments consisted of ice massage, dry-towel massage, and presence. Consecutive sampling was used to select 33 persons with AIDS who had neuropathic pain. Although the results of the study were negative, there was a decrease in pain intensity over time with both the ice massage and towel massage, suggesting that the intervention has some clinical benefit.

背景与目标： ：周围神经性疼痛是慢性疼痛的一种独特形式，可折磨多达50％的艾滋病患者。这项初步研究的目的是检验冰按摩对减轻神经性疼痛和改善睡眠质量的作用，并确定一项更大研究的可行性。使用了重复测量设计。这三种治疗包括冰按摩，干毛巾按摩和临场感。连续抽样选择了33名患有神经性疼痛的艾滋病患者。尽管研究结果为阴性，但冰按摩和毛巾按摩的疼痛强度均随时间降低，表明该干预措施具有一定的临床益处。

BACKGROUND & AIMS: CONTEXT:Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. OBJECTIVES:This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. METHODS:In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. RESULTS:The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. CONCLUSION:This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

背景与目标： 背景：晚期癌症患者的慢性疼痛提出了严峻的临床挑战。 Δ9-四氢大麻酚（THC）/大麻二酚（CBD）口腔粘膜喷雾剂（美国采用名称，nabiximols;Sativex®）是一种新型大麻素制剂，目前正在接受治疗，作为该治疗组的辅助疗法。
目的：这项随访研究调查了THC / CBD喷雾剂和THC喷雾剂在缓解晚期癌症患者的疼痛方面的长期安全性和耐受性。
方法：共有43例癌症相关疼痛患者尽管使用了阿片类药物长期服用，但仍没有足够的镇痛作用，他们参加了先前的三组试验（THC / CBD喷雾剂，THC喷雾剂或安慰剂），为期两周的父母随机对照试验，参加了这项开放性，多中心的后续研究。患者自行滴定THC / CBD喷雾剂（n = 39）或THC喷雾剂（n = 4）以缓解症状或最大剂量，并定期检查其安全性，耐受性和临床获益证据。
结果：THC / CBD喷剂患者每次就诊时，“疼痛严重程度”和“最严重疼痛”域的平均简短疼痛清单-简表得分的基线变化的功效终点显示出降低（即改善）。同样，欧洲癌症生活质量研究和治疗组织问卷-C30的得分显示，失眠，疼痛和疲劳程度较基线水平有所降低（即有所改善）。这项研究没有引起与THC / CBD喷雾剂的广泛使用相关的新安全隐患。
结论：这项研究表明，长期使用THC / CBD喷雾剂通常具有良好的耐受性，没有证据表明长期使用THC / CBD喷雾剂可减轻癌症相关疼痛。此外，继续使用研究药物的患者并未寻求随时间增加这种药物或其他缓解疼痛药物的剂量，这表明在与癌症相关的疼痛中辅助使用大麻素可提供有益的益处。

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。