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Bradykinin potentiates 5-HT3 receptor-mediated current in rat trigeminal ganglion neurons

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Acta Pharmacologica Sinica 2005年第4期26卷 428-434页

作者： Wang-ping HU~(1,2) Xue-mei LI~2 Ji-liang WU~3 Min ZHENG~3 Zhi-wang LI~4 2 Department of Physiology,3 Department of Pharmacology,Xianning College,Xianning 437100,China 4 Department of Neurobiology,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China DepartmentofPhysiology XianningCollegeXianning437100China

Aim:To explore the modulatory effect of bradykinin （BK） on 5-HT3receptor-mediated current in trigeminal ganglion （TG） neurons in ***:The whole-cell patch-clamp technique was used to record 5-HT-activated currents (I5-HT) inneurons freshly dissociated from rat *** were applied by rapid ***:The majority of the neurons examined responded to 5-HTapplied externally with an inward current （76.3%,74/97） that could be blocked bythe 5-HT3receptor antagonist,ICS-205,930 (1×10-6mol/L).In 66 of the 74 cellssensitive to 5-HT （89.2%）,pretreatment for 30 s with BK (1×10-6-1×10-10mol/L)could potentiate I5-HTwith the maximal modulatory effect occurring at10-7mol/L BK （71.6%+4.9%）.BK shifted the 5-HT concentration-response curveupwards with an increase of 68.9%±7.2% in the maximal current response,but withno significant change in the EC50value （19.1±3.2 μmol/L vs 20.9±3.5 μmol/L;t-test,P>0.05;n=8）.BK potentiated I5-HTin a holding potential-independent manner anddid not alter the reverse potential of *** BK-induced potentiation ofI5-HTwas almost completely blocked by Hoe 140 (5×10-7mol/L),a selective B2BKreceptor antagonist,and was removed after intracellular dialysis of GF-109203X（2 μmol/L）,a selective protein kinase C （PKC） inhibitor,with the re-patch ***:Pre-application of BK exerts an enhancing effect on I5-HTvia a PKC-dependent pathway in rat TG neurons,which may explain the peripheral'mecha-nism of pain and hyperalgesia caused by,for example,tissue damage andinflammation.

关键词： bradykinin 5-HT3 serotonin receptor regulation patch-clamp techniques trigeminal ganglion

Regulatory effects of anandamide on intracellular Ca^(2+) concentration increase in trigeminal ganglion neurons

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Neural Regeneration Research 2014年第8期9卷 878-887页

作者： Yi Zhang Hong Xie Gang Lei Fen Li Jianping Pan Changjin Liu Zhiguo Liu Lieju Liu Xuehong Cao Department of Anesthesiology Tongji Hospital Affiliated to Tongji Medical CollegeHuazhong University of Science and Technology Jingzhou Central Hospital Department of Physiology Tongji Medical CollegeHuazhong University of Science and Technology Department of Bioengineering Wuhan Institute of Engineering

Activation of cannabinoid receptor type 1 on presynaptic neurons is postulated to suppress neu- ~ ~ ~ 2＋ ~ ~ 2＋ rotransmlsslon by decreasing Ca reflux through high voltage-gated Ca channels. However, recent studies suggest that cannabinoids which activate cannabinoid receptor type 1 can increase neurotransmitter release by enhancing Ca2＋ influx in vitro. The aim of the present study was to investigate the modulation of intracellular Ca2＋ concentration by the cannabinoid receptor type 1 agonist anandamide, and its underlying mechanisms. Using whole cell voltage-damp and calcium imaging in cultured trigeminal ganglion neurons, we found that anandamide directly caused Ca2＋ influx in a dose-dependent manner, which then triggered an increase of intracellular Ca2＋ concentration. The cyclic adenosine and guanosine monophosphate-dependent protein kinase systems, but not the protein kinase C system, were involved in the increased intracellular Ca2＋concentration by anandamide. This result showed that anandamide increased intracellu- lar Ca2＋ concentration and inhibited high voltage-gated Ca2＋ channels through different signal transduction pathways.

关键词： nerve regeneration trigeminal ganglion neurons endocannabinoids anandamide can-nabinoid receptor type 1 voltage-dependent calcium channels vanilloid receptor patch-damp tech-nique calcium cyclic adenosine monophosphate protein kinase protein kinase C NIH grant neuralregeneration

Changes in P2Y purinoreceptor-mediated intracellular calcium signal pathways results in inositol-1, 4, 5-triphosphate-sensitive calcium stores in rat small trigeminal ganglion neurons

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Neural Regeneration Research 2010年第12期5卷 906-910页

作者： Yuanyin Wang Andong Liu Jie Lei Min Xie Zhongwen Li Liecheng Wang Stomatological Hospital Anhui Medical University Hefei 230032 Anhui Province China Department of Physiiology School of Basic Medical Science Anhui Medical University Hefei 230032 Anhui Province China

BACKGROUND： Most of the currently available information on purinergic receptors （P2Rs） involved in pain transmission is based on results obtained in dorsal root ganglion or the spinal cord. However, the mechanism of P2Rs in trigeminal neuralgia remains unclear. OBJECTIVE： To investigate changes in the P2R-mediated calcium signaling pathway in nociceptive trigemJnal ganglion neurons. DESIGN, TIME AND SETTING： In vitro experiments were conducted at the Patch-Clamp Laboratory of Comprehensive Experiment Center of Anhui Medical University, China from September 2008 to June 2009. MATERIALS： Thapsigargin, caffeine, suramin, and adenosine 5＇-triphosphate were purchased from Sigma, USA. METHODS： Using Fura-2-based microfluorimetry, intracellular calcium concentration （[Ca^2＋]i） was measured in freshly isolated adult rat small trigeminal ganglion neurons before and after drug application. MAIN OUTCOME MEASURES： Fluorescent intensities were expressed as the ratio F340/F380 to observe [Ca^2＋]i changes. RESULTS： In normal extracellular solution and Ca^2＋-free solution, application of thapsigargin （1 μmol/L）, a sarcoplasmic reticulum Ca^2＋ pump adenosine 5＇-triphosphate inhibitor, as well as caffeine （20 mmol/L）, a ryanodine receptor agonist, triggered [Ca^2＋]i increase in small trigeminal ganglion neurons. A similar response was induced by application of adenosine 5＇-triphosphate （100 μmol/L）. In Ca^2＋-free conditions, adenosine 5＇-triphosphate-induced [Ca^2＋]i transients in small trigeminal ganglion neurons were inhibited in cells pre-treated with thapsigargin （P 〈 0.01）, but not by caffeine （P 〉 0.05）. In normal, extracellular solution, adenosine 5＇-triphosphate-induced [Ca^2＋]i transients in small trigeminal ganglion neurons were partly inhibited in cells pre-treated with thapsigargin （P 〈 0.05）. CONCLUSION： Inositol-1,4, 5-triphosphate （IP3）- and ryanodine-sensitive Ca^2＋ stores exist in rat nociceptive trigeminal ganglion neurons. Two pathways are involved in the purinorec

关键词： calcium stores cytoplasmic calcium trigeminal ganglion adenosine 5'-triphosphate purinergic receptors neurotrophic factor trigeminal neuralgia neural regeneration

Facial pain induces the alteration of transient receptor potential vanilloid receptor 1 expression in rat trigeminal ganglion

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Neuroscience Bulletin 2007年第2期23卷 92-100页

作者：裴磊林传友戴甲培殷光甫华中科技大学同济医学院神经生物学系武汉430030

Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 （TRPV1） in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial inflammatory pain model was developed by subcutaneous injection of turpentine oil （TO） into rat facial area. Head withdrawal thermal latency （HWTL） and head withdrawal cold latency （HWCL） were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density （OD） value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion （TG）, peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis （Vc） on day 3, 5, 7, 14, and 21 after TO injection. Results HWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPV1-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive （IR） to TRPV1, and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae Ⅰ and the outer zone of laminae Ⅱ （Ⅱo） of Vc. Conclusion Facial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli, and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and terminal

关键词： vanilloid receptors facial pain hyperalgesia trigeminal ganglion

Histochemical Observation of Nitric Oxide Synthase in trigeminal ganglion of Rats with Experimental Pulpitis

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1999年第1期19卷 78-81页

作者：曹颖光邓云平 Department of Stomatology Tongji Hospital Tongji Medical University Wuhan 430030

Summary: In order to understand the roles of nitric oxide (NO) in pulpalgia and pulpitis, the histochemistry of nitric oxide synthase (NOS) in the neurons of trigeminal ganglion in experimental pulpitis rat and human inflammatory dental pulp tissues were histochemically studied by NADPH diaphorase (NADPH D) techniques. Results showed that NADPH D positive neurons were scattered in rat trigeminal ganglions, but the sizes of positive neurons were not changed. None of NOS positive fibers was found in human normal and inflammatory dental pulp tissues. The results suggested that NOS in trigeminal ganglion might play an important role in sensory transmission and regulation of pulpalgia. The absence of NOS positive nerves in human pulp suggested that NO may not be related to inflammatory stimulation and transmission in dental pulp tissues.

关键词： nitric oxide synthase histochemistry trigeminal ganglion pulpitis

Different roles of Notch signaling in the development of dorsal root ganglion and trigeminal ganglion

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Different roles of Notch signaling in the development of dor...

Hydrogen sulfide suppresses sustained potassium channel currents of trigeminal ganglion neurons

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Ze-Lan HU~1,Ming SHI~2,Ying HUANG~1,Min-Hua ZHENG~3,Zhe PEI~1,Jia-Yin CHEN~1,Hua HAN~3,Yu-Qiang DING~(1,*) 1 Department of Anatomy and Neurobiology,Tongji University School of Medicine,1239 Siping Road,Shanghai 200092,China 2 Department of Neurology,Xijing Hospital,Fourth Military Medical University,Xi''an 710032,China 3 Department of Medical Genetics and Developmental Biology,Fourth Military Medical University,Xi''an 710032, China

＜正＞Somatosensory ganglia including dorsal root ganglion（DRG） and trigeminal ganglion（TG） are derived from a common pool of neural crest stem cells（NCCs）,and are good systems to study the mechanisms of neurogenesis and *** signaling is known to play important roles in DRG and TG development,but the full scope of Notch functions in mammalian DRG and TG development remains poorly *** the present study,we used Wnt1-Cre to conditionally inactivate the transcription factor Rbpj,a critical integrator of activation signals from all Notch receptors,in NCCs and their derived *** of Rbpj caused the up-regulation of NeuroD1 and precocious neurogenesis in DRG early development but led to an eventual deficit of sensory neurons at later stages, due to reduced cell proliferation and abnormal cell *** addition,gliogenesis was delayed initially,but a nearcomplete loss of glia was observed finally in Rbpj-deficient ***,the phenotypes in TG show big differences compared with those in DRG in Rbpj CKO *** deletion of Rbpj also resulted in a reduction of sensory neurons at E16.5 in the TG,the precocious neurogenesis was not observed in TG early development. Furthermore,the initial gliogenesis at E10.0 in TG is also defective in the absence of Rbpj,but the normal distribution of glial cells was observed at E16.5 in the TG which contrasts with the complete loss of glial cells in the *** reason why the glial cells recover to the normal distribution density at later stages remained to be *** together,our data further elucidate the essential role of Rbpj in neurogenesis and gliogenesis during DRG and TG *** differences in phenotypes between DRG and TG indicate the function of Rbpj is diversified and context-dependent.

关键词： Notch signaling dorsal root ganglion trigeminal ganglion neurogenesis

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Hydrogen sulfide suppresses sustained potassium channel curr...

Implications of Transient Receptor Potential Cation Channels in Migraine Pathophysiology

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xing-Mei FENG~1,You-Lang ZHOU~2,Fei-Hu QI~2,Ning-Ang LIU~3,Guang-Yin XU~(3,*) 1 Department of Stomatology(Department of Oral and Maxillofacial Surgery),Affiliated Hospital of Nantong University,Nantong 226001,China 2 Jiangsu Key Laboratory of Neuroregeneration,Nantong University,Nantong 226001,China 3 Institute of Neuroscience,Key Laboratory of Pain Research & Therapy,Soochow University,Suzhou 215123,China

Objective Hydrogen sulfide(HS),an endogenous gaseotransmitter/modulator,is becoming appreciated that it may be involved in a wide variety of processes including inflammation and ***,the role and mechanism for HS in nociceptive processing in trigeminal ganglion(TG)neuron remains *** present study is to explore the role of HS on voltage-gated potassium channels and the distribution of endogenous HS synthyzing enzyme CBS expression in TG *** Whole cell patch clamp recordings were employed on acutely isolated TG neurons from adult male Sprague Dawley rats(6-8 week old).Immunofluorescence studies were carried out to determine whether CBS was co-expressed in Kv1.1 or Kv1.4-positive TG *** In rat TG,(77.0±6.6)%neurons were immunoreactive for CBS,(85.1±3.8)%for Kvl.l and(97.8±1.1)%for Kv1.4. Double staining showed that all the CBS labeled cells were Kvl.l and Kvl.4 positive,but only(92.2±6.1)%of Kvl.l and(78.2±9.9)%of Kv1.4 positive cells contained CBS,*** of HS donor NaHS(250μM)led to a significant depolarization of resting membrane potential recorded from TG neurons(n=8,P<0.05).Application of NaHS also resulted in a dramatic reduction in rheobase(P<0.05),hyperpolarization of action potential threshold (P<0.05),and a significant increase in the number of action potentials evoked at 2X and 3X rheobase stimulation (P<0.05).Under voltage-clamp conditions,TG neurons exhibited transient A-type(I)and sustained outward rectifier K currents(I).Application of NaHS did suppress the I density while did not change the I density of TG neurons (n=6).Conclusion These data suggest that HS generated by endogenously expressed CBS in TG neurons increases neuronal excitability,which is largely mediated by suppressing I density,thus identifying for the first time a specific molecular mechanism underlying pain and sensitization in TG.

关键词： cystathionine-β-synthetase trigeminal ganglion voltage-gated potassium channels excitability

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Neuroscience Bulletin 2021年第1期37卷 103-116页

作者： Mamoru Shibata Chunhua Tang Department of Neurology Keio University School of MedicineTokyo 160-8582Japan Department of Neurology Tokyo Dental College Ichikawa General HospitalChiba 272-8513Japan Department of Neurology and Center for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China

Migraine is a common and debilitating headache disorder. Although its pathogenesis remains elusive,abnormal trigeminal and central nervous system activity is likely to play an important role. Transient receptor potential(TRP) channels, which transduce noxious stimuli into pain signals, are expressed in trigeminal ganglion neurons and brain regions closely associated with the pathophysiology of migraine. In the trigeminal ganglion,TRP channels co-localize with calcitonin gene-related peptide, a neuropeptide crucially implicated in migraine pathophysiology. Many preclinical and clinical data support the roles of TRP channels in migraine. In particular,activation of TRP cation channel V1 has been shown to regulate calcitonin gene-related peptide release from trigeminal nerves. Intriguingly, several effective antimigraine therapies, including botulinum neurotoxin type A, affect the functions of TRP cation channels. Here, we discuss currently available data regarding the roles of major TRP cation channels in the pathophysiology of migraine and the therapeutic applicability thereof.

关键词： Migraine TRPV1 TRPM8 TRPA1 TRPV4 Calcitonin gene-related peptide trigeminal ganglion Neurogenic inflammation

Sensory innervation of the anterior eye segment in rats: aretrograde tracing study

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Frontiers of Medicine 2009年第3期3卷 352-356页

作者： Haixia LIU Zhiwang LI Min YANG Xiang TIAN Lei PEI Chaoying LI Department of Ophthalmology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Wuhan Institute of Neuroscience&Drug Research Jianghan UniversityWuhan 430056China Department of Neuroscience Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

This study aimed to investigate the sensory innervation of the anterior eye segment in rats by retrograde tracing with 1,1-dioleyl-3,3,3,3-tetrameth-ylindocarbocyanine,4-chlorobenesulfonate(FAST Dil)injected into the anterior *** sensory innervation of distinct elements of the anterior segment of the rat’s eye,*** cornea,ciliary body,iris,and trabecular meshwork,were studied by retrograde tracing using FAST Dil as a *** Dil was injected into the anterior chambers of the rat’s *** animals were sacriﬁced at different time points,i.e.,2,3,4,and 5 days after the *** Dil localization in trigeminal ganglions was studied with aﬂuorescent *** days after FAST Dil injection into the anterior chambers,the cornea,the ciliary body,the iris,and the trabecular meshwork were heavily *** in the ipsilateral trigeminal ganglion were also consistently *** number of labeled cells increased over time until 4 days after FAST Dil *** Dil-labeled neurons could be divided into two *** of the Dil-labeled neurons were concentrated in a sharp,longitudinal,spindle-like stripe,located in the dorso-medial side of the trigeminal ganglion,approximately two thirds of the dorsal *** other part of Dil-labeled neurons scattered laterally to the stripe,but just in one third of the dorsal ***,with our preliminary results,we conclude that the primary afferent sensory neurons innervating the rat’s anterior eye segments aggregate in the dorso-medial part of the ipsilateral trigeminal *** is feasible to identify them using retrograde tracing with FAST Dil anterior chamber injection.

关键词： trigeminal ganglion retrograde tracing