Magnetic field-driven induction of ZENK in the trigeminal system of pigeons (Columba livia)

Magnetoreception remains one of the few unsolved mysteries in sensory biology. The upper beak, which is innervated by the ophthalmic branch of the trigeminal nerve (V1), has been suggested to contain magnetic sensors based on ferromagnetic structures. Recently, its existence in pigeons has been seriously challenged by studies suggesting that the previously described iron-accumulations are macrophages, not magnetosensitive nerve endings. This raised the fundamental question of whether V1 is involved in magnetoreception in pigeons at all. We exposed pigeons to either a constantly changing magnetic field (CMF), to a zero magnetic field providing no magnetic information, or to CMF conditions after V1 was cut bilaterally. Using immediate early genes as a marker of neuronal responsiveness, we report that the trigeminal brainstem nuclei of pigeons, which receive V1 input, are activated under CMF conditions and that this neuronal activation disappears if the magnetic stimuli are removed or if V1 is cut. Our data suggest that the trigeminal system in pigeons is involved in processing magnetic field information and that V1 transmits this information from currently unknown, V1-associated magnetosensors to the brain.     

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca²⁺-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca²⁺-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca²⁺-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca²⁺-dependent exocytosis at different intensities of stimulation.     

The Molecular Basis and Pathophysiology of Trigeminal Neuralgia

Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.     

红光联合护理干预及药物治疗糖尿病合并带状疱疹神经痛的疗效观察

目的:探讨红光照射联合护理干预及药物治疗糖尿病合并带状疱疹神经痛的疗效。方法:选取此类患者56例,随机分为观察组和对照组,各28例。对照组用更昔洛韦加泼尼松、甲钴胺片、维生素B1片进行治疗,观察组在对照组治疗的基础上加用红光照射,两组护理干预方法保持一致,2周后评价疗效。结果:对照组治愈率为32.1%,总愈显率为60.7%,观察组上述数据分别为64.3%、89.3%,观察组疗效显著优于对照组。结论:红光照射联合护理干预及药物治疗糖尿病合并带状疱疹神经痛疗效显著,值得临床推广。     

鼠神经生长因子治疗肺癌并发带状疱疹神经痛的临床观察

目的:观察鼠神经生长因子联合椎旁神经根阻滞治疗肺癌併发带状疱疹神经痛的临床疗效。方法:将40例具有典型带状疱疹神经痛表现的肺癌患者随机分为A组(实验组)和B组(对照组)各20例。治疗组给予鼠神经生长因子肌注1支每日一次+椎旁神经根阻滞每周2次;对照组给予椎旁神经阻滞每周2次。观察治疗后1周、2周疼痛指标及1月后的随访结果。结果:比较两组患者的疼痛指标及总体疗效,A组优于B组,有显著性意义P0.05。结论:鼠神经生长因子联合椎旁神经根治疗肺癌伴带状疱疹神经痛优于单纯椎旁神经阻滞治疗。     

Taxon-specific differences in responsiveness to capsaicin and several analogues: Correlates between chemical structure and behavioral aversiveness

The present set of experiments was designed to explore avian insensitivity to capsaicin. Based upon a molecular model of avian chemosensory repellency, we hypothesized that structural modifications of the basic capsaicin molecule, which is itself not aversive to birds, might produce aversive analogues. To this end, European starlings (Sturnus vulgaris) and Norway rats (Rattus norvegicus) were given varied concentrations of synthetic capsaicin and four analogues (methyl capsaicin, veratryl amine, veratryl acetamide, vanillyl acetamide) in feeding and drinking tests. The results agreed with a model that we are developing to describe the chemical nature of avian repellents. Synthetic capsaicin and vanillyl acetamide were not repellent to birds, owing to the presence of an acidic phenolic OH group. Conversely, veratryl acetamide was aversive, due to the basic nature of this compound. For rats, repellent effectiveness among compounds was reversed: synthetic capsaicin was the best repellent while veratryl acetamide was the worst. We speculate that this taxonomic reversal may reflect basic differences in trigeminal chemoreception. In any case, it is clear that chemical correlates of mammalian repellents are opposite to those that predict avian repellency.     

Chronic Orofacial Pain: Models,Mechanisms, and Genetic and Related Environmental Influences

Chronic orofacial pain conditions can be particularly difficult to diagnose and treat because of their complexity and limited understanding of the mechanisms underlying their aetiology and pathogenesis. Furthermore, there is considerable variability between individuals in their susceptibility to risk factors predisposing them to the development and maintenance of chronic pain as well as in their expression of chronic pain features such as allodynia, hyperalgesia and extraterritorial sensory spread. The variability suggests that genetic as well as environmental factors may contribute to the development and maintenance of chronic orofacial pain. This article reviews these features of chronic orofacial pain, and outlines findings from studies in animal models of the behavioural characteristics and underlying mechanisms related to the development and maintenance of chronic orofacial pain and trigeminal neuropathic pain in particular. The review also considers the role of environmental and especially genetic factors in these models, focussing on findings of differences between animal strains in the features and underlying mechanisms of chronic pain. These findings are not only relevant to understanding underlying mechanisms and the variability between patients in the development, expression and maintenance of chronic orofacial pain, but also underscore the importance for considering the strain of the animal to model and explore chronic orofacial pain processes.     

Analgesic Effect of Tranilast in an Animal Model of Neuropathic Pain and Its Role in the Regulation of Tetrahydrobiopterin Synthesis

Trigeminal neuralgia is unilateral, lancinating, episodic pain that can be provoked by routine activities. Anticonvulsants, such as carbamazepine, are the drugs of choice; however, these possess side-effects. Microvascular decompression is the most effective surgical technique with a higher success rate, although occasionally causes adverse effects. The potential treatment for this type of pain remains unmet. Increased tetrahydrobiopterin (BH4) levels have been reported in association with axonal injury. This study aimed to evaluate the effect of tranilast on relieving neuropathic pain in animal models and analyze the changes in BH4 synthesis. Neuropathic pain was induced via infraorbital nerve constriction. Tranilast, carbamazepine, or saline was injected intraperitoneally to assess the rat’s post-intervention pain response. In the von Frey’s test, the tranilast and carbamazepine groups showed significant changes in the head withdrawal threshold in the ipsilateral whisker pad area. The motor coordination test showed no changes in the tranilast group, whereas the carbamazepine group showed decreased performance, indicating impaired motor coordination. Trigeminal ganglion tissues were used for the PCR array analysis of genes that regulate the BH4 pathway. Downregulation of the sepiapterin reductase (Spr) and aldoketo reductase (Akr) genes after tranilast injection was observed compared to the pain model. These findings suggest that tranilast effectively treats neuropathic pain.     

单、双径向轴承安装时三叉式万向联轴器的附加弯矩分析

为找出三叉式万向联轴器在安装和使用过程中出现振动、噪声的原因,分析采用单、双径向轴承安装三叉式万向联轴器输出轴时联轴器附加弯矩随输入轴转角及偏转角的分布规律。首先建立2种安装方式下联轴器的运动简图,应用空间机构坐标变换技术建立输入轴与输出轴的关系方程,推导出系统存在偏转角时输出轴的运动方程,表明输出轴采用单径向轴承安装时三叉式万向联轴器为准等角速传动,采用双径向轴承安装时其具有等角速传动特性。其次分析这2种安装方式下作用在输入轴和输出轴上的附加弯矩分量,根据虚位移原理确定三叉式万向联轴器输出轴在2种安装方式下系统均出现附加弯矩。通过分析发现:采用单径向轴承安装时,存在偏转弯矩,且一个运动周期内附加弯矩的波动频率是输入轴的3倍,呈正弦曲线变化,且附加弯矩的变化趋势为随偏转角的增大呈直线上升;双径向轴承安装时,偏转弯矩为零,附加弯矩随偏转角的增大而逐渐增大,未出现波动。结果表明:2种安装方式下三叉式万向联轴器上均产生附加弯矩,从而使系统产生振动效应。该结果对研究系统产生振动的原因、确定系统非线性动力学行为具有重要的意义。     

TRPA1-Mediated Src Family Kinases Activity Facilitates Cortical Spreading Depression Susceptibility and Trigeminovascular System Sensitization

Transient receptor potential ankyrin 1 (TRPA1) plays a role in migraine and is proposed as a promising target for migraine therapy. However, TRPA1-induced signaling in migraine pathogenesis is poorly understood. In this study, we explored the hypothesis that Src family kinases (SFKs) transmit TRPA1 signaling in regulating cortical spreading depression (CSD), calcitonin gene-related peptide (CGRP) release and neuroinflammation. CSD was monitored in mouse brain slices via intrinsic optical imaging, and in rats using electrophysiology. CGRP level and IL-1β gene expression in mouse trigeminal ganglia (TG) was detected using Enzyme-linked Immunosorbent Assay and Quantitative Polymerase Chain Reaction respectively. The results showed a SFKs activator, pYEEI (EPQY(PO3H2)EEEIPIYL), reversed the reduced cortical susceptibility to CSD by an anti-TRPA1 antibody in mouse brain slices. Additionally, the increased cytosolic phosphorylated SFKs at Y416 induced by CSD in rat ipsilateral cerebral cortices was attenuated by pretreatment of the anti-TRPA1 antibody perfused into contralateral ventricles. In mouse TG, a SFKs inhibitor, saracatinib, restored the CGRP release and IL-1β mRNA level increased by a TRPA1 activator, umbellulone. Moreover, umbellulone promoted SFKs phosphorylation, which was reduced by a PKA inhibitor, PKI (14–22) Amide. These data reveal a novel mechanism of migraine pathogenesis by which TRPA1 transmits signaling to SFKs via PKA facilitating CSD susceptibility and trigeminovascular system sensitization.