Long-term potentiation in the anterior cingulate cortex and chronic pain

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli from the periphery ‘teach’ humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time. Conventional pain medicines often fail to control chronic pain. Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain. Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex, and such persistent potentiation does not require continuous neuronal activity from the periphery. At the synaptic level, potentiation of excitatory transmission caused by injuries may be mediated by the enhancement of glutamate release from presynaptic terminals and potentiated postsynaptic responses of AMPA receptors. Preventing, ‘erasing’ or reducing such potentiation may serve as a new mechanism to inhibit chronic pain in patients in the future.     

Role of changes in the transmembrane ion currents in pathological states of the body

Modern data of study of transmembrane ions currents (through the sodium-potassium- and calcium-channels) in the mechanism of pathological pain syndromes were reviewed. Tetrodotoxyn-resistant sodium currents, abnormal combinations of different types of sodium-channels during the inflammation, neuropathies (syndromes hyperalgesii and allodonii) and diabetic neuropathy analyzed. The role of pain sensitivity transmitters was demonstrated. Nerve Grow Factor plays the important role in the sodium-channels genes expression. Different types of transmembrane calcium currents participated in hyperalgesium and hypoalgesium analyzed. The summary mechanism of pain suggested as voltage-calcium-channels activation and transsynaptic NMDA receptors excitation that should be conductive the neurons hyperexcitation and force of synaptic transmission.     

中国大鲵繁殖生物学研究进展

中国大鲵（Amndrias davidiamus Blanchard）是我国特有濒危的两栖物种,是研究生物进化、生物多样性、性别决定分子机制等的好材料,对于科学研究具有巨大的潜在贡献。近年来人们对它的研究力度不断加大,本文综述厂大鲵的繁殖生物学的近期研究工作,也简要探讨了大鲵繁殖生物学今后研究的主要工作,以期为大鲵繁殖生物学及繁殖技术的进一步的研究提供有价值的参考。     

Affective empathy and prosocial behavior in rodents

Empathy is an essential function for humans as social animals. Emotional contagion, the basic form of afffective empathy, comprises the cognitive process of perceiving and sharing the affective state of others. The observational fear assay, an animal model of emotional contagion, has enabled researchers to undertake molecular, cellular, and circuit mechanism of this behavior. Such studies have revealed that observational fear is mediated through neural circuits involved in processing the affective dimension of direct pain experiences. A mouse can also respond to milder social stimuli induced by either positive or negative emotional changes in another mouse, which seems not dependent on the affective pain circuits. Further studies should explore how different neural circuits contribute to integrating different dimensions of affective empathy.     

中国大鲵研究进展

中国大鲵是我国特有濒危的两栖物种,是研究生物进化、生物多样性、性别决定分子机制等问题的好材料。近年来,人们对它的研究力度不断加大,著述颇多。本文对大鲵的生态保护、解剖发育、生理生化、遗传进化等方面的近期研究资料进行了整理和回顾,也简要探讨了今后大鲵研究的主要工作,以期为研究者们提供有价值的资料。     

Companion-Animals’ Effectiveness in Managing Chronic Pain in Adult Community Members

ABSTRACT

Therapy animals have been found to alleviate pain in healthcare settings, but companion-animal owners report greater discomfort and use more analgesics than people who do not own one or more companion animals. To investigate this anomaly, 173 adults completed an online survey that included questions about themselves and any companion animal they owned, the Depression Anxiety and Stress Scales, the Numeric Pain Rating Scale, and a modified version of the Chronic Pain Coping Inventory-42. Participants were also invited to contact the researchers to expand on their responses in a semi-structured interview, to which seven owners responded. There was no significant difference between reported pain levels in owners versus non-owners. However, companion-animal owners who reported actively using human–animal interactions to manage their pain rated this as moderately helpful and reported lower pain levels than other owners. There were also no significant differences between owners’ and non-owners’ anxiety or stress levels. Companion-animal owners reported more depressive symptoms than non-owners, but owners with animals perceived as more friendly reported fewer depressive symptoms. Dog owners comprised most of the sample and, for these participants, there was a negative association between perceived dog friendliness and levels of depression and anxiety. Those with more disobedient dogs also experienced greater stress. Interviewees reported that their companion animals helped them cope with pain in many ways, including provision of social and emotional support and by providing a sense of purpose in life. These findings indicate that some, but not all, companion animals may be beneficial for participants with chronic pain. Since the benefits appear to be associated with the species and personality of the animal, and with whether the person actively uses human–animal interactions as a pain-coping mechanism, care should be taken before recommending companion-animal ownership to persons suffering from chronic pain.     

Altered Neuronal–Glial Signaling in Glutamatergic Transmission as a Unifying Mechanism in Chronic Pain and Mental Fatigue

Recent experimental results have demonstrated a glial activation during long-term pain that produces and releases cytokines, free oxygen radicals, nitric oxide, and other neuroactive substances in the spinal cord dorsal horns. Such activation might generate a vicious circle by increasing the neuronal excitability level due to a decreased astroglial glutamate uptake and thereby reinforce pain signals that travel up to the thalamus and further up into the parietal cortex for identification and interpretation. In this paper, we adapt new knowledge on neuronal-glial signaling in the CNS to develop tentative explanations at the cellular level for the maintenance of pain signals in the brain, for formation of "pain memory," and even for the increased pain sensitivity that persons with chronic pain often experience in body regions other than those originally affected. We also suggest a hypothetical mechanism at the cellular level underlying the mental fatigue from which persons with chronic pain may suffer. This hypothesis relies on the impaired astroglial glutamate uptake capacity due to the production of neuroactive substances, altered conditions in the chronic pain state, and the anxiety and stress reactions that may occur secondary to the pain. Neuronal activity over time in the dysfunctional state of the astroglial network leads to an increase in extracellular glutamate levels in the vicinity of glutamate synapses. In turn, this increase leads over time to less precision in glutamate transmission. The increased extracellular glutamate levels lead to increased excitability and increased energy requirements. When cellular energy decreases the glutamate transmission decreases, and according to our hypothesis, this is one cause of mental fatigue. New strategies for treatment of chronic pain and the associated mental fatigue are formulated and should be explored.     

禽流感病毒感染鸽的流行病学与致病机理研究进展

禽流感病毒(Avian influenza virus,AIV)不仅严重危害禽类,而且对人类生命健康造成严重威胁。鸽作为留鸟,具有作为AIV从野生鸟类传播至人类中间宿主的潜能。鸽对AIV的易感性以及在病毒传播中的作用却存在争议。通过分析AIV自然感染、人工感染鸽的流行病学以及实验研究数据,同时回顾了禽流感病毒感染鸽的机制,发现随着病毒的进化和时间的推移,鸽群AIV的感染率也在递增;尤其随着近年具有双受体结合特性的高致病性禽流感病毒(highly pathogenic avian influenza virus,HPAIV)clade2.3.4.4分支H5Nx毒株的出现,其感染鸽后排毒量上升以及鸽体间直接接触传播能力增强。为了有效防控AIV的跨种间传播,有必要加强对鸽感染AIV的流行病学监测和传播特性的研究,特别需要密切关注具双受体结合特性的H5Nx和H7N9 HPAIV对鸽易感性的发展趋势。     

谷氨酸性突触在痛觉和记忆中的突触和分子机制

谷氨酸是哺乳动物脑中的兴奋性递质。中枢神经系统的谷氨酸性突触广泛参与痛觉传递,突触可塑性和递质的调节。谷氨酸的NMDA受体参与前脑相关的学习及功能。在这篇综述中,我们提出前脑的NMDA受体通过增强谷氨酸性突触传递导致长期性的炎痛。具有增强NMDA受体功能的小鼠会产生更多的慢性痛。NMDA NR2B受体抑制剂在未来可能被用来控制人类的慢性痛。     

Catechol-O-methyltransferase polymorphisms do not play a significant role in pain perception in male Chinese Han population

Polymorphisms in the human catechol-O-methyltransferase (COMT) gene have been widely studied for their role in pain and analgesia. In this study, sensitivity to potassium iontophoresis, visual analog scale measurements for fixed twofold pain threshold stimulation and pain threshold changes induced by transcutaneous electrical acupoint stimulation (TEAS) were assessed in a population of healthy Chinese males. These results were correlated with the alleles of six single nucleotide polymorphisms (SNP) or diplotypes of common haplotypes designated as low pain sensitive, average pain sensitive, and high pain sensitive in the COMT gene of these subjects. Our results reveal that the alleles of each SNP are not significantly correlated with pain perception except for the rs4633 allele in the 2 Hz TEAS session (P < 0.05). In addition, the six diplotypes of COMT haplotypes, which cover 92.5% of the Chinese population, are also not correlated with pain perception. Moreover, there were no significant differences in pain threshold changes induced by 2 and 100 Hz TEAS among the diplotypes of each SNP or the various haplotypes. These results suggest that COMT activity do not play a significant role in pain perception and TEAS-induced analgesia in the Chinese Han male population.     

Neuromedin U receptor 2-deficient mice display differential responses in sensory perception, stress, and feeding

Neuromedin U (NMU) is a highly conserved neuropeptide with a variety of physiological functions mediated by two receptors, peripheral NMUR1 and central nervous system NMUR2. Here we report the generation and phenotypic characterization of mice deficient in the central nervous system receptor NMUR2. We show that behavioral effects, such as suppression of food intake, enhanced pain response, and excessive grooming induced by intracerebroventricular NMU administration were abolished in the NMUR2 knockout (KO) mice, establishing a causal role for NMUR2 in mediating NMU's central effects on these behaviors. In contrast to the NMU peptide-deficient mice, NMUR2 KO mice appeared normal with regard to stress, anxiety, body weight regulation, and food consumption. However, the NMUR2 KO mice showed reduced pain sensitivity in both the hot plate and formalin tests. Furthermore, facilitated excitatory synaptic transmission in spinal dorsal horn neurons, a mechanism by which NMU stimulates pain, did not occur in NMUR2 KO mice. These results provide significant insights into a functional dissection of the differential contribution of peripherally or centrally acting NMU system. They suggest that NMUR2 plays a more significant role in central pain processing than other brain functions including stress/anxiety and regulation of feeding.     

Social transmission of face preferences among humans

Previous studies demonstrating mate choice copying effects among females in non-human species have led many researchers to propose that social transmission of mate preferences may influence sexual selection for male traits. Although it has been suggested that social transmission may also influence mate preferences in humans, there is little empirical support for such effects. Here, we show that observing other women with smiling (i.e. positive) expressions looking at male faces increased women's preferences for those men to a greater extent than did observing women with neutral (i.e. relatively negative) expressions looking at male faces. By contrast, the reverse was true for male participants (i.e. observing women with neutral expressions looking at male faces increased male participant's preferences for those men to a greater extent than did observing women smiling at male faces). This latter finding suggests that within-sex competition promotes negative attitudes among men towards other men who are the target of positive social interest from women. Our findings demonstrate that social transmission of face preferences influences judgments of men's attractiveness, potentially demonstrating a mechanism for social transmission of mate preferences.     

Screening and characterization of human monoglyceride lipase active site inhibitors using orthogonal binding and functional assays

Endocannabinoids such as 2-arachidonylglycerol (2-AG) are ligands for cannabinoid receptors that contribute to the transmission and modulation of pain signals. The antinociceptive effect of exogenous 2-AG suggests that inhibition of monoglyceride lipase (MGLL), the enzyme responsible for degrading 2-AG and arresting signaling, may be a target for pain modulation. Here we describe the characterization of MGLL ligands following a high-throughput screening campaign. Ligands were discovered using ThermoFluor, a label-free affinity-based screening tool that measures ligand binding via modulation of protein thermal stability. A kinetic fluorescent assay using the substrate 4-methylcoumarin butyrate was used to counterscreen confirmed HTS positives. A comparison of results from binding and inhibition assays allowed elucidation of compound mechanism of action. We demonstrate the limit of each technology and the benefits of using orthogonal assay techniques in profiling compounds.     

Antinociceptive and nociceptive actions of opioids

Although the opioids are the principal treatment options for moderate to severe pain, their use is also associated with the development of tolerance, defined as the progressive need for higher doses to achieve a constant analgesic effect. The mechanisms which underlie this phenomenon remain unclear. Recent studies revealed that cholecystokinin (CCK) is upregulated in the rostral ventromedial medulla (RVM) during persistent opioid exposure. CCK is both antiopioid and pronociceptive, and activates descending pain facilitation mechanisms from the RVM enhancing nociceptive transmission at the spinal cord and promoting hyperalgesia. The neuroplastic changes elicited by opioid exposure reflect adaptive changes to promote increased pain transmission and consequent diminished antinociception (i.e., tolerance).     

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.     

生物多样性数据论文发表趋势分析

近年来有关科学数据共享的呼声越来越高, 基于同行评审的生物多样性数据论文也受到越来越多的关注, 并出现了一些专门发表数据论文的数据期刊。本文总结了近年来生物多样性数据发表方面的进展, 选择两本代表性数据期刊(Biodiversity Data Journal和Scientific Data), 分析了它们自创刊以来的发文数量、涉及生物类群、文章浏览量和被引次数等指标。结果显示两本数据期刊的发文量都呈稳步增长趋势, 其生物多样性数据论文覆盖了包括动物界、植物界、真菌界在内的众多生物类群, 文章浏览量和被引次数方面也有可喜的表现, 说明数据论文正在被越来越多的研究者所接受。对文章作者国别的分析则显示了不同地区的研究者在发表生物多样性数据论文或数据共享方面的不均衡。建议相关领域的中国研究者和期刊关注生物多样性数据论文和数据共享政策, 更多地践行数据共享。     

角蒿生物碱及镇痛活性物质

角蒿(Incarvillea sinensis)为透骨草的主要来源之一,称为“羊角透骨草”,具有祛风除湿、消肿止痛之功效。从其全草分离得到了多种新的单萜生物碱和大环精胺类生物碱,其中单萜生物碱之一角蒿酯碱(incarvillateine),具有很强的镇痛活性,且作用机理不同于吗啡。角蒿酯碱已成为开发新型非麻醉性镇痛新药的重要先导化合物,本文对角蒿的化学成分、镇痛活性、作用机理和构效关系的研究作一综述。     

成年小鼠前脑NMDA受体参与神经元的动作电位发放

谷氨酸是中枢神经系统主要的快速兴奋性递质。AMPA受体和海人藻酸受体主要参与突触传递,而NMDA受体主要参与突触可塑性。基因操作的方法增强NMDA受体的功能,可以增强动物在正常生理状态下的学习能力,及在组织损伤情况下的反应敏感性。NMDA受体参与生理功能的主要机制是长时程增强（long—term potentiation,LTP）。我们的研究表明,NMDA受体不仅参与刺激前扣带皮层的第五层细胞或刺激白质诱导的突触反应,而且参与在胞体施加去极化跃阶电流诱导的动作电位的发放。钙一钙调蛋白敏感的腺苷酸环化酶1（adenylyl cyclase 1,AC1）和cAMP信号通路可能介导了这些反应。由于扣带皮层神经元在伤害性刺激和痛中发挥重要作用,我们的结果为前脑NMDA受体参与突触传递和动作电位发放,以及与前脑相关的行为,如感受伤害性刺激和痛,提供了一个新的机制。