排序方式: 共有44条查询结果,搜索用时 15 毫秒
1.
Swarnalakshmi Raman Arief Waskitho Resmi Raju Takuma Iwasa Daisuke Ikutame Kazuo Okura Masamitsu Oshima Yoshizo Matsuka 《International journal of molecular sciences》2022,23(11)
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. 相似文献
2.
Nele Lefeldt Dominik Heyers Nils-Lasse Schneider Svenja Engels Dana Elbers Henrik Mouritsen 《Journal of the Royal Society Interface》2014,11(100)
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. 相似文献
3.
QiLiang Chen Dae Ik Yi Josiah Nathan Joco Perez Monica Liu Steven D. Chang Meredith J. Barad Michael Lim Xiang Qian 《International journal of molecular sciences》2022,23(7)
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. 相似文献
4.
J. Russell Mason N. Jay Bean Pankaj S. Shah Larry Clark 《Journal of chemical ecology》1991,17(12):2539-2551
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. 相似文献
5.
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. 相似文献
6.
Mariia Belinskaia Tomas Zurawski Seshu Kumar Kaza Caren Antoniazzi J. Oliver Dolly Gary W. Lawrence 《International journal of molecular sciences》2022,23(2)
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. 相似文献
7.
Various explanations for the pathophysiology of migraines have been proposed; however, none of these provide a complete explanation. The author critically reviews previous theories and proposes a new molecular theory of migraine pathophysiology. The diagnosis of primary headaches is generally based on clinical histories and symptoms only because there is no reliable diagnostic examination. The author proposes a new classification system and set of diagnostic criteria for headaches based on molecular markers. 相似文献
8.
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。 相似文献
9.
Lingdi Nie Liwen Jiang John P. Quinn Blair D. Grubb Minyan Wang 《International journal of molecular sciences》2021,22(22)
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. 相似文献
10.
Mako Naniwa Chihiro Nakatomi Suzuro Hitomi Kazunari Matsuda Takuya Tabuchi Daijiro Sugiyama Sayaka Kubo Yuichi Miyamura Kenichi Yoshino Sumio Akifusa Kentaro Ono 《International journal of molecular sciences》2021,22(22)
Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca2+ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca2+ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL® are needed to sufficiently induce the therapeutic effects. 相似文献