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： : 交感神经的维持性疼痛可以通过交感神经传出和传入伤害性纤维之间的触感相互作用来介导，也可以通过儿茶酚胺诱导的伤害性神经末梢的激活来介导。我们在此报告了一名患有交感持续疼痛的患者的C伤害感受器的单纤维记录，其中交感神经阻滞反复消除了双腿的持续疼痛。我们根据八种C纤维的机械响应性和与活动有关的传导速度减慢 (在0.125Hz下20个脉冲的0.5/-1.1与7.1/-2.0 ms的潜伏期增加)，将它们分类为机械敏感的伤害感受器。强烈的内源性交感神经爆发后，两根C纤维被激活，延迟数秒; 在将去甲肾上腺素 (10 microl，0.05%) 注射到其神经支配区域后，它们也被兴奋约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 6.0，10μl) 而延长的活化以及前列腺素E2注射后它们的热响应的敏化，证明了它们的传入性质。此外，对于机械不敏感的伤害感受器，它们的活性依赖性减慢是典型的。我们得出的结论是，内源性释放的儿茶酚胺可以激活敏感的机械不敏感伤害感受器，从而可能导致交感疼痛。没有发现交感传出和伤害性传入纤维之间的触觉相互作用的证据。

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：

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： : 脊髓NMDA受体激活后过度兴奋可能导致慢性疼痛。天然衍生的哺乳动物肽组织蛋白可能具有NMDA拮抗剂活性。这项研究探讨了稳定的类似物 [Ser1] 组织蛋白 (SHG) 可以减轻慢性疼痛的可能性。使用慢性收缩损伤模型 (CCI) 诱发神经病理性疼痛。鞘内注射SHG可显着减轻由CCI引起的痛觉过敏和异常性疼痛，几乎使反应正常化。这些结果表明，天然肽组织粒蛋白可能是神经性疼痛管理的新型辅助手段。

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： : 周围神经性疼痛是一种独特的慢性疼痛形式，困扰多达50% 的艾滋病患者。这项初步研究的目的是检查冰按摩减轻神经性疼痛和改善睡眠质量的效果，并确定进行更大规模研究的可行性。使用了重复测量设计。这三种治疗方法包括冰按摩，干毛巾按摩和在场。连续抽样选择33例患有神经性疼痛的艾滋病患者。尽管研究结果为阴性，但随着时间的推移，冰按摩和毛巾按摩的疼痛强度有所降低，这表明该干预措施具有一定的临床益处。

BACKGROUND & AIMS: :The advance of mitral valve repair techniques through tissue engineering is impeded by the lack of information regarding the cellular and extracellular components of the mitral valve. The present study aims to expand our understanding of the mitral valve structure by analysing the synthesis of extracellular matrix (ECM) proteins and the expression of nitric oxide synthase (NOS). Valvular endothelial cells (VECs) and valvular interstitial cells (VICs) were isolated from porcine mitral valves. Immunochemical staining of ECM components, including type I, II, III, IV and V collagen, laminin, fibronectin, elastin and chondroitin sulphate (CS), was performed on both mitral valve tissue and cell cultures. Reverse transcription polymerase chain reaction and immunochemistry were used to analyse NOS expression in native valve and in culture. Both VECs and VICs synthesised the basement membrane components, laminin and type IV collagen both in vivo and in vitro, amongst other fibrous ECM proteins. Synthesis of type I collagen and CS was absent in VEC cultures. Each cell type had a characteristic profile of NOS expression. VECs synthesised endothelial NOS both in vivo and in vitro, with a minority of VICs expressing neuronal NOS in vitro. The present study reports newly recognised aspects of the mitral valve structure and the in vitro behaviour of mitral valve cell populations based on ECM synthesis and NOS expression. The presented profiles can be used as base tools for the generation of data necessary for the selection of ideal cell sources and for the design of appropriate scaffolds for the development of effective tissue-engineered mitral valves.

背景与目标： : 缺乏有关二尖瓣细胞和细胞外成分的信息，阻碍了通过组织工程进行二尖瓣修复技术的发展。本研究旨在通过分析细胞外基质 (ECM) 蛋白的合成和一氧化氮合酶 (NOS) 的表达来扩大我们对二尖瓣结构的理解。从猪二尖瓣分离瓣膜内皮细胞 (VECs) 和瓣膜间质细胞 (VICs)。对二尖瓣组织和细胞培养物进行了ECM成分的免疫化学染色，包括I，II，III，IV和V型胶原蛋白，层粘连蛋白，纤连蛋白，弹性蛋白和硫酸软骨素 (CS)。逆转录聚合酶链反应和免疫化学用于分析天然瓣膜和培养物中NOS的表达。VECs和VICs均在体内和体外合成了基底膜成分，层粘连蛋白和IV型胶原蛋白以及其他纤维ECM蛋白。在VEC培养物中没有I型胶原蛋白和CS的合成。每种细胞类型都有NOS表达的特征。VECs在体内和体外合成了内皮NOS，少数VICs在体外表达神经元NOS。本研究报告了基于ECM合成和NOS表达的二尖瓣结构和二尖瓣细胞群体的体外行为的新认识。所呈现的配置文件可用作基础工具，用于生成选择理想细胞源所需的数据以及设计用于开发有效组织工程二尖瓣的适当支架。

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：

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： 内脏疼痛的感知是一个复杂的过程，涉及脊髓和高阶脑结构。越来越多的证据表明肠道菌群是大脑和行为的关键调节剂，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大脑结构。GF小鼠表现出内脏超敏反应，并伴有脊髓中Toll样受体和细胞因子基因表达的增加，这通过出生后用常规定植 (CC) 的微生物群定植而标准化。在GF小鼠中，前扣带回皮层 (ACC) 和导水管周围灰色 (涉及疼痛处理的区域) 的体积分别减少和扩大，并且ACC的树突状变化明显。这些发现表明，正常的内脏疼痛感需要肠道菌群。

BACKGROUND & AIMS: :Accurate muscle geometry (muscle length and moment arm) is required to estimate muscle function when using musculoskeletal modelling. In shoulder, muscles are often modelled as a collection of independent line segments, leading to non-physiological muscles trajectory, especially for the rotator cuff muscles. To prevent this, a surface mesh model was developed and validated against 7 MRI positions in one participant. Mean moment arm errors was 11.4% for the line vs. 8.8% for the mesh model. While the model with independent lines led to some non-physiological trajectories, the mesh model gave lower misestimations of muscle lengths and moment arms.

背景与目标： : 使用肌肉骨骼模型时，需要准确的肌肉几何形状 (肌肉长度和力矩臂) 来估计肌肉功能。在肩部，肌肉通常被建模为独立线段的集合，从而导致非生理肌肉轨迹，尤其是对于肩袖肌肉。为了防止这种情况，开发了一个表面网格模型，并针对一名参与者的7个MRI位置进行了验证。11.4% 直线的平均力矩臂误差与网格模型的8.8%。虽然具有独立线条的模型导致了一些非生理轨迹，但网格模型对肌肉长度和力矩臂的误判较低。

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： : 已在50例与癌症相关的严重疼痛患者中评估了使用固定在常规16号硬膜外导管上的皮下植入门静脉系统的可行性。该技术允许以8-12小时的间隔经皮硬膜外施用吗啡以控制疼痛。植入的平均持续时间为12周，而原位保留的最长时间为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)，注射系统有八次阻塞。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 (25号) 模拟300注射，并通过光学和扫描电子显微镜检查注射物。两种类型的针头都会导致颗粒污染，推荐的Huber点针头会更大。

BACKGROUND & AIMS: :In this editorial, we propose that the association between depression and cardiovascular disease may be conceptualised as a continuous, bidirectional process that originates in youth. The paper byÅberg and colleagues in this issue adds to this literature showing that low cardiovascular fitness at adolescence increases the risk of future depression.

背景与目标： : 在这篇社论中，我们建议抑郁症与心血管疾病之间的关联可以概念化为一个持续的，双向的过程，起源于青年。这期的论文by å berg及其同事补充了这些文献，表明青春期心血管健康水平低会增加未来抑郁症的风险。

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： 神经性疼痛是周围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。然而，这些机制的复杂性以及尚处于起步阶段的转化疼痛研究的相对年轻，阻碍了成功的基础研究转化为人类治疗。大多数临床上可用的神经性疼痛治疗方法都是从其他治疗领域借来的，例如抗抑郁药和抗癫痫药，或者涉及应用较旧的治疗方法，例如阿片类药物。齐康宁、他喷他多和高浓度辣椒素贴剂是例外。与所有其他镇痛剂相似，这些镇痛剂仅可部分缓解患者的疼痛。慢性神经性疼痛患者的护理标准是多模式和多学科。为了使大多数患者达到并保持令人满意的疼痛缓解，必须结合治疗剂，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: :This study examined the validity of commonly used regression equations for the Actigraph and Actical accelerometers in predicting energy expenditure (EE) in children and adolescents. Sixty healthy (8-16 yrs) participants completed four treadmill (TM) and five self-paced activities of daily living (ADL). Four Actigraph (AG) and three Actical (AC) regression equations were used to estimate EE. Bias (± 95% CI) and root mean squared errors were used to assess the validity of the regression equations compared with indirect calorimetry. For children, the Freedson (AG) model accurately predicted EE for all activities combined and the Treuth (AG) model accurately predicted EE for TM activities. For adolescents, the Freedson model accurately predicted EE for TM activities and the Treuth model accurately predicted EE for all activities and for TM activities. No other equation accurately estimated EE. The percent agreement for the AG and AC equations were better for light and vigorous compared with moderate intensity activities. The Trost (AG) equation most accurately classified all activity intensity categories. Overall, equations yield inconsistent point estimates of EE.

背景与目标： : 这项研究检验了Actigraph和Actical加速度计常用回归方程在预测儿童和青少年能量消耗 (EE) 中的有效性。60名健康 (8-16岁) 的参与者完成了四项跑步机 (TM) 和五项日常生活的自定进度活动 (ADL)。使用四个Actigraph (AG) 和三个Actical (AC) 回归方程来估计EE。与间接量热法相比，使用偏差 (± 95% CI) 和均方根误差来评估回归方程的有效性。对于儿童，Freedson (AG) 模型准确地预测了所有组合活动的EE，而Treuth (AG) 模型准确地预测了TM活动的EE。对于青少年，Freedson模型准确地预测了TM活动的EE，而Treuth模型准确地预测了所有活动和TM活动的EE。没有其他方程准确估计EE。与中等强度的活动相比，AG和AC方程的百分比一致性对于光和活力更好。Trost (AG) 方程最准确地对所有活动强度类别进行了分类。总的来说，方程产生不一致的EE点估计。

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：

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：