神经递质和调质参与导水管周围灰质痛觉调控的研究进展

导水管周围灰质(periaqueductal gray,PAG)在疼痛的调控过程中处于一个不可或缺的位置.其不仅是痛觉信息上行传递的重要部位,还是疼痛抑制系统的重要组成部分.在PAG,包括γ-氨基丁酸(γ-aminobutyric acid,GABA)、5-羟色胺(5-hydroxytryptamine,5-HT)和谷氨酸(glutamate,Glu)在内的神经递质以及内源性阿片肽(endogenous opioid peptides,EOP)和内源性大麻素(endocannabinoid,e CB)为代表的神经调质都参与了PAG对疼痛的信息传递以及调节.本文重点综述GABA、5-HT、Glu、EOP和eCB在PAG参与疼痛生理调控机制的研究进展,以期为中枢神经系统的镇痛研究提供一定的理论基础.     

Review: Assessment of completeness of reporting in intervention studies using livestock: an example from pain mitigation interventions in neonatal piglets

Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources.     

Current issues in fish welfare

Human beings may affect the welfare of fish through fisheries, aquaculture and a number of other activities. There is no agreement on just how to weigh the concern for welfare of fish against the human interests involved, but ethical frameworks exist that suggest how this might be approached. Different definitions of animal welfare focus on an animal's condition, on its subjective experience of that condition and/or on whether it can lead a natural life. These provide different, legitimate, perspectives, but the approach taken in this paper is to focus on welfare as the absence of suffering. An unresolved and controversial issue in discussions about animal welfare is whether non‐human animals exposed to adverse experiences such as physical injury or confinement experience what humans would call suffering. The neocortex, which in humans is an important part of the neural mechanism that generates the subjective experience of suffering, is lacking in fish and non‐mammalian animals, and it has been argued that its absence in fish indicates that fish cannot suffer. A strong alternative view, however, is that complex animals with sophisticated behaviour, such as fish, probably have the capacity for suffering, though this may be different in degree and kind from the human experience of this state. Recent empirical studies support this view and show that painful stimuli are, at least, strongly aversive to fish. Consequently, injury or experience of other harmful conditions is a cause for concern in terms of welfare of individual fish. There is also growing evidence that fish can experience fear‐like states and that they avoid situations in which they have experienced adverse conditions. Human activities that potentially compromise fish welfare include anthropogenic changes to the environment, commercial fisheries, recreational angling, aquaculture, ornamental fish keeping and scientific research. The resulting harm to fish welfare is a cost that must be minimized and weighed against the benefits of the activity concerned. Wild fish naturally experience a variety of adverse conditions, from attack by predators or conspecifics to starvation or exposure to poor environmental conditions. This does not make it acceptable for humans to impose such conditions on fish, but it does suggest that fish will have mechanisms to cope with these conditions and reminds us that pain responses are in some cases adaptive (for example, suppressing feeding when injured). In common with all vertebrates, fish respond to environmental challenges with a series of adaptive neuro‐endocrine adjustments that are collectively termed the stress response. These in turn induce reversible metabolic and behavioural changes that make the fish better able to overcome or avoid the challenge and are undoubtedly beneficial, in the short‐term at least. In contrast, prolonged activation of the stress response is damaging and leads to immuno‐suppression, reduced growth and reproductive dysfunction. Indicators associated with the response to chronic stress (physiological endpoints, disease status and behaviour) provide a potential source of information on the welfare status of a fish. The most reliable assessment of well‐being will be obtained by examining a range of informative measures and statistical techniques are available that enable several such measures to be combined objectively. A growing body of evidence tells us that many human activities can harm fish welfare, but that the effects depend on the species and life‐history stage concerned and are also context‐dependent. For example, in aquaculture, adverse effects related to stocking density may be eliminated if good water quality is maintained. At low densities, bad water quality may be less likely to arise whereas social interactions may cause greater welfare problems. A number of key differences between fish and birds and mammals have important implications for their welfare. Fish do not need to fuel a high body temperature, so the effects of food deprivation on welfare are not so marked. For species that live naturally in large shoals, low rather than high densities may be harmful. On the other hand, fish are in intimate contact with their environment through the huge surface area of their gills, so they are vulnerable to poor water quality and water borne pollutants. Extrapolation between taxa is dangerous and general frameworks for ensuring welfare in other vertebrate animals need to be modified before they can be usefully applied to fish. The scientific study of fish welfare is at an early stage compared with work on other vertebrates and a great deal of what we need to know is yet to be discovered. It is clearly the case that fish, though different from birds and mammals, however, are sophisticated animals, far removed from unfeeling creatures with a 15 s memory of popular misconception. A heightened appreciation of these points in those who exploit fish and in those who seek to protect them would go a long way towards improving fish welfare.     

Anti-allodynic effect of 2-(aminomethyl)adamantane-1-carboxylic acid in a rat model of neuropathic pain: A mechanism dependent on CaV2.2 channel inhibition

Neuropathic pain is a serious physical disabling condition resulting from lesion or dysfunction of the peripheral sensory nervous system. Despite the fact that the mechanisms underlying neuropathic pain are poorly understood, the involvement of voltage-gated calcium (Ca_V) channels in its pathophysiology has justified the use of drugs that bind the Ca_V channel α₂δ auxiliary subunit, such as gabapentin (GBP), to attain analgesic and anti-allodynic effects in models involving neuronal sensitization and nerve injury. GBP binding to α₂δ inhibits nerve injury-induced trafficking of the α₁ pore forming subunits of Ca_V channels, particularly of the N-type, from the cytoplasm to the plasma membrane of pre-synaptic terminals in dorsal root ganglion neurons and dorsal horn spinal neurons. In the search for alternative forms of treatment, in this study we describe the synthesis and pharmacological profile of a GABA derivative, 2-aminoadamantane-1-carboxylic acid (GZ4), which displays a close structure–activity relationship with GBP. Behavioral assessment using von Frey filament stimuli showed that GZ4 treatment reverted mechanical allodynia/hyperalgesia in an animal model of spinal nerve ligation-induced neuropathic pain. In addition, using the patch clamp technique we show that GZ4 treatment significantly decreased whole-cell currents through N-type Ca_V channels heterologously expressed in HEK-293 cells. Interestingly, the behavioral and electrophysiological time course of GZ4 actions reflects that its mechanism of action is similar but not identical to that of GBP. While GBP actions require at least 24 h and imply uptake of the drug, which suggests that the drug acts mainly intracellularly affecting channels trafficking to the plasma membrane, the faster time course (1–3 h) of GZ4 effects suggests also a direct inhibition of Ca²⁺ currents acting on cell surface channels.     

Upregulation of miR-183 represses neuropathic pain through inhibiton of MAP3K4 in CCI rat models

Many studies have verified that microRNAs contribute a lot to neuropathic pain progression. Furthermore, nerve-related inflammatory cytokines play vital roles in neuropathic pain progression. miR-183 has been identified to have a common relationship with multiple pathological diseases. However, the potential effects of miR-183 in the process of neuropathic pain remain undetermined. Therefore, we performed the current study with the purpose of finding the functions of miR-183 in neuropathic pain progression using a chronic sciatic nerve injury (CCI) rat model. We demonstrated that miR-183 expression levels were evidently reduced in CCI rats in contrast with the control group. Overexpression of miR-183 produced significant relief of mechanical hyperalgesia, as well as thermal hyperalgesia in CCI rats. Furthermore, neuropathic pain-correlated inflammatory cytokine expression levels containing interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) were obviously inhibited by upregulation of miR-183. Meanwhile, dual-luciferase reporter assays showed MAP3K4 was a direct downstream gene of miR-183. The expression levels of MAP3K4 were modulated by the increased miR-183 negatively, which lead to the downregulation of IL-6, IL-1β, and COX-2, and then reduced neuropathic pain progression, respectively. Overall, our study pointed out that miR-183 was a part of the negative regulator which could relieve neuropathic pain by targeting MAP3K4. Thus it may provide a new clinical treatment for neuropathic pain patients clinical therapy.     

视前区微量注射吗啡对大鼠丘脑束旁核痛反应神经元电活动的影响

本实验观察了视前区(POA)内微量注入阿片样物质对丘脑束旁核(Pf)痛反应神经元电活动影响。结果如下:(1)POA 内微量注射高浓度吗啡(10μg/μl)能显著抑制 Pf 内大部分(20/26)痛兴奋神经元(PEN)的痛诱发放电,其中3个神经元注药后对伤害性刺激转变成抑制反应;POA 内微量注射低浓度吗啡(1μg/μl)也显著抑制 Pf 内大部分(19/23)PEN 的痛诱发放电。(2) POA 内微量注射两种浓度的吗啡,均使大多数痛抑制神经元(PIN,共27/33)的完全抑制时程缩短。上述结果提示,POA 内阿片样物质对 Pf 内痛反应神经元的电活动可能具有抑制作用。     

压脚痛阈测定法的改进和应用

本文介绍一种改进的压脚测痛法。采用电机驱动替代用手挤压橡皮球完成升压过程;通过一个自动的电路切断结构判定抽脚反应,较目视更加客观;用读数保持电路记录压力变化,较直接读取刻度值更加准确,可靠。这些优点,业经电针和吗啡镇痛实验验证。     

纸坊病病毒病因的研究

1985年4～10月与1986年6～8月,在贵州省沿河县的纸坊村和崔家坨村先后发生了病因不明的传染病。纸坊村约有1/5的村民发病,病死率为12％,崔家坨村有1/10的村民发病,病死率高达30％。发病波及各年龄组,以青壮年为多,有家庭集聚现象。 本病起病急,轻症者只有头晕、乏力、肌痛、多汗、心悸伴以低热,有的初期有短暂的腹泻。重症者有高热(40℃以上)、大汗、心悸、游走性肌肉痉挛伴有明显疼痛和触痛,以腰骶部及四肢肌肉为好发部位。病人烦燥不安,2～5天内死亡。经实验室检查,排除了食物中毒、农药中毒、钩端螺旋体病和弓形体感染。从病人和接触者的粪便中分离到9株病毒,性状一致,为RNA型25nm的球形颗粒,耐酸,耐乙醚,能凝集人“O”型血球。经血清学鉴定为ECHO3型病毒。16份病人双份血清的检测结果表明,恢复期血清对该病毒中和抗体有4倍以上升高者共8例(纸坊村和崔家坨各4例)。病人单份血清也都有较高的抗体。有理由认为两年中先后在两个村庄发生的传染病与ECHO3型病毒有密切关系。查阅文献,尚未见有关ECHO3型病毒引起以肌痛、游走性肌痉挛为特征的疾病的报道。     

Electro and acoustic myography for noninvasive assessment of lumbar paraspinal muscle function

In 31 normal subjects (17 male), aged 19-48 years, and 8 patients with chronic low back pain (4 male), aged 37-55 years, the repeatability of surface recordings of acoustic myography (AMG) and electromyography (EMG) were examined in the lumbar paraspinal muscles. Five isometric test positions were examined. In 21 of the normal subjects, four positions tested were: quiet standing, half extension from prone lying, full extension from prone with and without resistance. In 10 of the normal subjects and the 8 back pain patients, a standardised, unsupported horizontal position with the upper body over the end of a couch was tested. The AMG and EMG signals were full-wave rectified and integrated (iAMG and iEMG). The variability of recordings during repeated 5-s isometric contractions was assessed by analysis of variance (ANOVA) and the coefficient of variation (CV) was calculated from the ANOVA. Both recording techniques produced the most repeatable results during the unsupported, horizontal hold position. In the normal subjects, CV were, iAMG 5.6%, iEMG 4.9%; and in the patients, iAMG 4.4%, iEMG 2.6%. The CV for the other four isometric test positions ranged from 15.3% to 29.4% for iAMG, and 8% to 15.7% for iEMG. These results demonstrated that a controlled test manoeuvre for examining AMG and EMG of the paraspinal muscles was vital for repeatable recordings. The CV for the standardised, horizontal position were lower than for previously published results.(ABSTRACT TRUNCATED AT 250 WORDS)     

刺激蓝斑对下丘脑弓状核单位放电的影响

本研究室以往工作表明,下丘脑弓状核(ARC)和蓝斑(LC)在痛觉调制和针刺镇痛中具有重要作用。本实验观察刺激 LC 对清醒制动大鼠 ARC 单位放电的影响。ARC 单位对刺激LC 的反应以抑制为主,在38个单位中有23个单位呈现抑制反应。ARC 单位对外周伤害性刺激的反应以兴奋为主,在27个单位中有20个单位呈现兴奋反应。刺激 LC 可以使 ARC 单位的伤害性反应的持续时间明显缩短。α_2受体激动剂(氯压啶)和α_1受体阻断剂(酚苄明)能加快ARC 单位的平均放电频率,而β-受体激动剂(异丙基肾上腺素)和β受体阻断剂(心得安)则无明显影响。这些结果提示 LC 的去甲肾上腺素能神经元对 ARC 神经元的作用是通过α受体实现的。