Influence of segmental and extra-segmental conditioning stimuli on cortical potentials evoked by painful electrical stimulation

This study evaluated the effects of two different types of segmental/extra-segmental conditioning stimuli (tonic muscle pain and non-painful vibration) on the subjective experience (perceived pain intensity) and on the cortical evoked potentials to standardized test stimuli (cutaneous electrical stimuli). Twelve subjects participated in two separate sessions to investigate the effects of tonic muscle pain or cutaneous vibration on experimental test stimuli. The experimental protocol contained a baseline registration (test stimuli only), a registration with the test stimuli in combination with the conditioning stimuli, followed by a registration with the test stimuli only. In addition, the effects of the conditioning stimuli were examined at two anatomically separated locations (segmental and extra-segmental). Compared with the test stimulus alone, the perceived pain intensity and peak-to-peak amplitudes of the evoked potentials were unchanged in the presence of non-painful conditioning stimuli at either location. In contrast, a significant decrease of the perceived pain intensity and peak-to-peak amplitudes was found in the presence of painful conditioning stimuli at the extra-segmental sites. Moreover, the topographic maps of the 32-channel recordings suggested that the distribution of the scalp evoked potentials was almost symmetrical around the vertex Cz in the baseline registration. The evoked potentials were generally decreased during hypertonic saline infusion at the extra-segmental sites, but the distribution of the topographic maps did not appear to change. Vibration has previously been shown to inhibit pain, but in the present study the perceived intensity of phasic painful electrical stimuli was unchanged. The reduced perceived pain intensity and the smaller peak-to-peak amplitude of the evoked potential in the presence of extra-segmental conditioning pain are in accordance with the concept of diffuse noxious inhibitory control.     

Toll-like Receptor 2 Mediates Peripheral Nerve Injury-induced NADPH Oxidase 2 Expression in Spinal Cord Microglia

We have previously reported that NADPH oxidase 2 (Nox2) is up-regulated in spinal cord microglia after spinal nerve injury, demonstrating that it is critical for microglia activation and subsequent pain hypersensitivity. However, the mechanisms and molecules involved in Nox2 induction have not been elucidated. Previous studies have shown that Toll-like receptors (TLRs) are involved in nerve injury-induced spinal cord microglia activation. In this study, we investigated the role of TLR in Nox2 expression in spinal cord microglia after peripheral nerve injury. Studies using TLR knock-out mice have shown that nerve injury-induced microglial Nox2 up-regulation is abrogated in TLR2 but not in TLR3 or -4 knock-out mice. Intrathecal injection of lipoteichoic acid, a TLR2 agonist, induced Nox2 expression in spinal cord microglia both at the mRNA and protein levels. Similarly, lipoteichoic acid stimulation induced Nox2 expression and reactive oxygen species production in primary spinal cord glial cells in vitro. Studies on intracellular signaling pathways indicate that NF-κB and p38 MAP kinase activation is required for TLR2-induced Nox2 expression in glial cells. Conclusively, our data show that TLR2 mediates nerve injury-induced Nox2 gene expression in spinal cord microglia via NF-κB and p38 activation and thereby may contribute to spinal cord microglia activation.     

Coarse Architecture of the Transient Receptor Potential Vanilloid 1 (TRPV1) Ion Channel Determined by Fluorescence Resonance Energy Transfer

The transient receptor potential vanilloid 1 ion channel is responsible for the perception of high temperatures and low extracellular pH, and it is also involved in the response to some pungent compounds. Importantly, it is also associated with the perception of pain and noxious stimuli. Here, we attempt to discern the molecular organization and location of the N and C termini of the transient receptor potential vanilloid 1 ion channel by measuring FRET between genetically attached enhanced yellow and cyan fluorescent protein to the N or C terminus of the channel protein, expressed in transfected HEK 293 cells or Xenopus laevis oocytes. The static measurements of the domain organization were mapped into an available cryo-electron microscopy density of the channel with good agreement. These measurements also provide novel insights into the organization of terminal domains and their proximity to the plasma membrane.     

Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization

Multiple Ca²⁺-dependent processes are involved in capsaicin-induced desensitization of transient receptor potential vanilloid 1 (TRPV1), but desensitization of TRPV1 by heat occurs even in the absence of extracellular Ca²⁺, although the mechanisms are unknown. In this study, we tested the hypothesis that capsaicin and heat desensitize TRPV1 through distinct mechanisms involving distinct structural segments of TRPV1. In HEK293 cells that heterologously express TRPV1, we found that heat-induced desensitization was not affected by the inclusion of intracellular ATP or alanine mutation of Lys¹⁵⁵, both of which attenuate capsaicin-induced desensitization, suggesting that heat-induced desensitization occurs through mechanisms distinct from capsaicin-induced desensitization. To determine protein domains involved in heat-induced desensitization, we generated chimeric proteins between TRPV1 and TRPV3, a heat-gated channel lacking heat-induced desensitization. We found that TRPV1 with the carboxyl-terminal domain (CTD) of TRPV3 retained heat activation but was impaired in heat-induced desensitization. Further experiments using chimeric or deletion mutants within TRPV1 CTD indicated that the distal half of CTD regulates the activation and desensitization of TRPV1 in modality-specific manners. Within the distal CTD, we identified two segments that distinctly regulated capsaicin- and heat-induced desensitization. The results suggest that the activation and desensitization of TRPV1 by capsaicin and heat can be modulated differentially and disproportionally through different regions of TRPV1 CTD. Identifying the domains involved in thermal regulation of TRPV1 may facilitate the development of novel anti-hyperalgesic approaches aimed at attenuating activation and enhancing desensitization of TRPV1 by thermal stimuli.     

Serum level of brain-derived neurotrophic factor in fibromyalgia syndrome correlates with depression but not anxiety

Brain-derived neurotrophic factor (BDNF) has been known to play a role in fibromyalgia syndrome (FMS) patients. Depression and anxiety are quite common additional symptoms in FMS. However the role of BDNF in these symptoms still needs to be elucidated. Although BDNF has been shown to be relevant in major depression, however studies could not show such differences between FMS patients with and without major depression. As mood-related symptom occurs frequently and differs in its intensity in FMS patients, BDNF level should be measured in subgroup regarding depression and anxiety scale. Therefore the aim of this study was to evaluate the correlation of BDNF in serum of FMS with intensity of depression and anxiety. Additionally, interleukin (IL)-6 was measured.     

基于FMEA和POSSUM评分的手术风险评估研究

??????? 目的 研究建立手术风险评估的架构,以正确决策手术时机。方法 采用用于计数死亡率和并发症发生率的生理学和手术严重性（POSSUM）评分原理进行分层计分,同时引用失效模式与效应分析方法对手术可能发生故障模式的严重度及发生可能性及风险因素的影响度3个维度进行评估。结果 建立了手术前风险预警机制及手术评估架构,利用评估架构对某综合医院2010年200例80岁高龄的手术病人进行了术前评估,结果手术后并发症的发生率较2009年同年龄的手术病人的并发症下降了10.45%。结论 在手术前对手术相关因素进行评估,可以为手术时机的选择提供参考。     

Acid-sensing ion channels (ASICs): therapeutic targets for neurological diseases and their regulation

Extracellular acidification occurs not only in pathological conditions such as inflammation and brain ischemia, but also in normal physiological conditions such as synaptic transmission. Acid-sensing ion channels (ASICs) can detect a broad range of physiological pH changes during pathological and synaptic cellular activities. ASICs are voltage-independent, proton-gated cation channels widely expressed throughout the central and peripheral nervous system. Activation of ASICs is involved in pain perception, synaptic plasticity, learning and memory, fear, ischemic neuronal injury, seizure termination, neuronal degeneration, and mechanosensation. Therefore, ASICs emerge as potential therapeutic targets for manipulating pain and neurological diseases. The activity of these channels can be regulated by many factors such as lactate, Zn²⁺, and Phe-Met-Arg-Phe amide (FMRFamide)-like neuropeptides by interacting with the channel’s large extracellular loop. ASICs are also modulated by G protein-coupled receptors such as CB₁ cannabinoid receptors and 5-HT₂. This review focuses on the physiological roles of ASICs and the molecular mechanisms by which these channels are regulated. [BMB Reports 2013; 46(6): 295-304]     

化疗联合冷循环射频消融术治疗原发性肝癌的效果分析

目的：探讨化疗联合冷循环射频消融术治疗原发性肝癌的疗效及安全性。方法：108例原发性肝癌患者随机分为两组,均给予灌注化疗,每4周进行一次灌注化疗,对照组（n=54）进行3次,治疗组（n=54）只进行一次。治疗组给予冷循环射频消融术。评价生活质量Kamofsky评分,治疗前后检查患者的血、尿、便常规,肝肾功能（包括天冬氨酸转氨酶、丙氨酸转氨酶（AVr）、白蛋白（ALB）、总胆红素、肌酐及尿素氮等指标）,甲胎蛋白（AFP）,T细胞亚群和加强肝脏CT扫描。随访1年,经CT确定肝癌复发。结果：治疗组Kamofsky评分有效率为59．26％,对照组Kamofsky评分有效率为37．03％,两组Kamofsky评分有效率相比较,差异有统计学意义（P〈0．05）。两组治疗后症状变化相比较,除腹胀外其余各项指标差异均有统计学意义（P〈O．05）。治疗后两组相比较,ALT和AFP差异有统计学意义（P〈0．05）。治疗后两组T细胞亚群变化相比较,治疗组各项指标均变化显著（P〈0．05）。治疗后随访一年,治疗组复发率为22．22％;对照组复发率为53．70％。两组治疗一年后复发率相比较,差异有统计学意义（P〈0．05）。结论：化疗结合冷循环射频消融术治疗原发性肝癌疗效肯定,并发症及副作用小,复发率低。     

不同麻醉和术后镇痛方式对中老年胸科手术后胰岛素抵抗的影响

目的：探讨不同麻醉和术后镇痛方式对中老年胸科手术后胰岛素抵抗的影响。方法：中老年胸科手术患者80例随机分为治疗组与对照组各40例,两组都采用开胸手术治疗,于手术结束前30min硬膜外腔给予镇痛,治疗组采用舒芬太尼镇痛,对照组采用地佐辛镇痛。结果：两组镇痛后2h与镇痛后24h的HR和MVP对比差异明显（P〈0．05）,同时对照组不同时间点的组内对比差异明显（P〈0．05）,治疗组组内对比无明显差异。治疗组在镇痛后2h与镇痛后24h的VAS评分都明显少于对照组（P〈0．05）,Ramsay评分治疗组高于对照组（P〈0．05）。治疗组组内不同时间点胰岛素含量和胰岛素敏感性对比无明显差异,而对照组对比差异明显（P〈0．05）,同时镇痛后组间对比也有明显差异（P〈0．05）。结论：相对于地佐辛,舒芬太尼用于中老年胸科手术术后疼痛镇痛效果良好,能有效地抑制胰岛素抵抗与应激反应的发生,有很好的应用效果。     

唑来膦酸联合99Tc-MDP治疗肿瘤多发骨转移的临床价值

目的:探讨唑来膦酸联合99Tc-MDP(云克)治疗多发骨转移瘤的临床价值.方法:将40例确诊为肿瘤伴骨转移的病人,随机分为两组.观察组22例,使用唑来膦酸联合99Tc-MDP治疗;对照组18例,单独使用99Tc-MDP治疗,均治疗3周后比较两组治疗前后骨痛的变化情况、骨转移灶的治疗情况及不良反应的发生情况.结果:观察组和对照组的止痛总有效率分另为95.5％和66.7％,差异有统计学意义(P＜0.05).观察组和对照组骨转移灶的治疗总有效率分别为36.3％和27.7％,差异有统计学意义(P＜0.05).此外,两组治疗过程中均偶见不同程度的发热,但不良反应的发生率并无统计学差异(P＞0.05).结论:唑来膦酸联合99Tc-MDP治疗多发骨转移瘤的止痛效果及骨转移灶的疗效显著优于单纯99Tc-MDP治疗,且毒副作用无明显增加.