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Science Advances:成牙细胞TRPC5通道是牙齿冷痛的信号,可作为治疗牙痛的新靶点

2021-03-30 MedSci原创 MedSci原创

对于有蛀牙的人来说,喝冷饮可能会引起牙神经痛,那牙齿冷信号的传导机制是怎样的呢?

龋齿是一种慢性疾病,牙齿表面的细菌生物膜与可发酵的碳水化合物基质结合,导致脱矿,最终导致蛀牙。全世界有24亿人的恒牙龋齿未经治疗。发炎的牙齿对寒冷极为敏感,被认为是一种短而剧烈的神经痛。在功能解剖学的基础上,牙髓的感觉神经丛被广泛认为是机械性和伤害性疼痛。

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“这是一种独特的疼痛,”霍华德休斯医学院(HHMI)副院长兼首席科学官David Clapham教授说:“这太折磨人了。”

现在,他和一个国际科学家团队已经弄清了牙齿是如何感知寒冷的,并确定了参与其中的分子和细胞因素。研究小组在2021年3月26日的Science Advances杂志上报道,在小鼠和人类身上,称为成牙本质细胞(odontoblasts)的牙齿细胞含有检测温度下降的冷敏感蛋白。这些细胞发出的信号最终会引发大脑的剧烈疼痛。

这项研究解释了一种古老的家庭疗法是如何缓解牙痛的。德国弗里德里希-亚历山大大学的电生理学家Katharina Zimmermann教授领导了这项研究。她说,丁香油的主要成分含有一种化学物质,可以阻止“冷传感器”蛋白质的产生,丁香油在牙科领域已经使用了几个世纪。

开发针对这种传感器的更具体的药物有可能消除牙齿对寒冷的敏感。一旦你找到了目标分子,就有了治疗的可能性。

没有人知道牙齿是如何感知寒冷的,科学家们提出了一个主要的理论:当温度变化时,牙齿内的微小沟渠会流动液体。一些研究人员认为,神经可以以某种方式感知这一运动的方向,从而发出牙齿是冷是热的信号。

“我们不能排除这个理论,”但是没有任何直接的证据支持它,HHMI的的神经生物学家Clapham说。牙齿中的液体运动和牙齿生物学一般来说都很难研究。科学家必须切开牙釉质——人体最坚硬的物质和另一层叫做牙本质的坚硬层,所有这些都不能粉碎牙齿柔软的牙髓及其内部的血管和神经。齐默尔曼说,有时,整颗牙齿“只会摔成碎片”。

Zimmermann和Clapham及他们的研究小组并没有打算研究牙齿。他们的工作主要集中在离子通道,细胞膜上的小孔。在检测到一个信号——例如化学信息或温度变化——通道要么关闭要么张开,这就产生了一个电脉冲,从一个细胞到另一个细胞。这是一种快速传递信息的方式,对大脑、心脏和其他组织至关重要。

大约15年前,当Zimmermann在Clapham的实验室做博士后时,研究小组发现一种叫做TRPC5的离子通道对寒冷非常敏感。但是不知道TRPC5的冷感应能力在体内的何处发挥作用。他们发现反正不是皮肤。研究小组2011年在美国国家科学院院刊上发表报告说,缺乏离子通道的老鼠仍能感觉到寒冷。

在那之后,“我们进入了死胡同,”Zimmermann说。有一天,这个团队正坐在一起吃午饭,讨论这个问题:身体里还有什么组织能感觉到寒冷呢?答案是牙齿。

TRPC5对于炎症性牙痛是必需的

麻省总医院的病理学家Jochen Lennerz是这项研究的合著者,他在检查了成年人类的标本后发现,TRPC5确实存在于牙齿中,而且在有龋齿的牙齿中更是如此。

在老鼠身上进行的一项新实验使研究人员确信,TRPC5确实具有冷传感器的功能。Zimmermann的研究小组没有把牙齿敲开,只在培养皿中观察了整个系统:颌骨、牙齿和牙齿神经。研究小组记录了当冰溶液接触牙齿时的神经活动。在正常的小鼠中,寒冷触发了神经活动,但在缺乏TRPC5的小鼠或使用了阻断离子通道的化学物质的牙齿中则没有。

牙齿的痛觉感受器对冷的反应比皮肤的痛觉感受器对冷的反应大得多

研究小组追踪了TRPC5在牙髓和牙本质之间的成牙本质细胞的位置。当一个牙本质暴露的人咬冰棒的时候,那些TRPC5细胞会感觉到寒冷并发出“噢!”信号传输到大脑。让你感觉到非一般的疼痛!

这种敏锐的感觉还没有像其他科学领域那样得到广泛的研究。牙痛可能不是一个时髦的话题,“但它很重要,影响着很多人。”

参考文献:Laura Bernal, Pamela Sotelo-Hitschfeld, Christine König, Viktor Sinica, Amanda Wyatt, Zoltan Winter, Alexander Hein, Filip Touska, Susanne Reinhardt, Aaron Tragl, Ricardo Kusuda, Philipp Wartenberg, Allen Sclaroff, John D. Pfeifer, Fabien Ectors, Andreas Dahl, Marc Freichel, Viktorie Vlachova, Sebastian Brauchi, Carolina Roza, Ulrich Boehm, David E. Clapham, Jochen K. Lennerz, Katharina Zimmermann. Odontoblast TRPC5 channels signal cold pain in teethScience Advances, 2021; 7 (13): eabf5567 DOI: 10.1126/sciadv.abf5567

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    2021-05-02 楼伊森

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    2021-04-01 lsndxfj
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    2021-04-01 jichang
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    2021-04-01 zhouqu_8
  5. [GetPortalCommentsPageByObjectIdResponse(id=962265, encodeId=9cba962265e6, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=20205491090, createdName=楼伊森, createdTime=Sun May 02 11:56:33 CST 2021, time=2021-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288319, encodeId=d9fa1288319b7, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376270, encodeId=059513e6270e8, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1430238, encodeId=dd04143023831, content=<a href='/topic/show?id=b58f6e691fc' target=_blank style='color:#2F92EE;'>#牙齿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67691, encryptionId=b58f6e691fc, topicName=牙齿)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952423, encodeId=483f95242340, content=赚积分, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e97c5474600, createdName=卢晓静, createdTime=Tue Mar 30 17:14:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952463, encodeId=5d80952463e2, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd275394824, createdName=ms3000000796987452, createdTime=Tue Mar 30 19:58:21 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952448, encodeId=f75495244864, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Mar 30 18:57:57 CST 2021, time=2021-03-30, status=1, ipAttribution=)]
    2021-03-30 卢晓静

    赚积分

    1

    展开1条回复
  6. [GetPortalCommentsPageByObjectIdResponse(id=962265, encodeId=9cba962265e6, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=20205491090, createdName=楼伊森, createdTime=Sun May 02 11:56:33 CST 2021, time=2021-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288319, encodeId=d9fa1288319b7, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376270, encodeId=059513e6270e8, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1430238, encodeId=dd04143023831, content=<a href='/topic/show?id=b58f6e691fc' target=_blank style='color:#2F92EE;'>#牙齿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67691, encryptionId=b58f6e691fc, topicName=牙齿)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952423, encodeId=483f95242340, content=赚积分, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e97c5474600, createdName=卢晓静, createdTime=Tue Mar 30 17:14:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952463, encodeId=5d80952463e2, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd275394824, createdName=ms3000000796987452, createdTime=Tue Mar 30 19:58:21 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952448, encodeId=f75495244864, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Mar 30 18:57:57 CST 2021, time=2021-03-30, status=1, ipAttribution=)]
    2021-03-30 ms3000000796987452

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=962265, encodeId=9cba962265e6, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=20205491090, createdName=楼伊森, createdTime=Sun May 02 11:56:33 CST 2021, time=2021-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288319, encodeId=d9fa1288319b7, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376270, encodeId=059513e6270e8, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1430238, encodeId=dd04143023831, content=<a href='/topic/show?id=b58f6e691fc' target=_blank style='color:#2F92EE;'>#牙齿#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67691, encryptionId=b58f6e691fc, topicName=牙齿)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Apr 01 06:13:48 CST 2021, time=2021-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952423, encodeId=483f95242340, content=赚积分, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e97c5474600, createdName=卢晓静, createdTime=Tue Mar 30 17:14:55 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952463, encodeId=5d80952463e2, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd275394824, createdName=ms3000000796987452, createdTime=Tue Mar 30 19:58:21 CST 2021, time=2021-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=952448, encodeId=f75495244864, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Mar 30 18:57:57 CST 2021, time=2021-03-30, status=1, ipAttribution=)]
    2021-03-30 jyzxjiangqin

    好文章!

    0

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