颞下颌关节神经分布的研究

颞下颌关节神经分布的研究 颞下颌关节神经分布及神经免疫物质的研究(综述) 颞下颌关节紊乱病(temporomandibular disorder，TMD)是口腔疾病中的常见病之一，由于病因复杂，治愈率低，已被国内外学者所日益重视，是近年来国内外口腔医学重点研究的课题之一。过去的研究多集中于肌肉功能异常、牙合关系异常、关节囊薄弱 [1]以及自身免疫因素等方面的临床研究。而近年来的临床工作中发现，神经系统也可能参与了关节疾病的病变过程。如?关节滑膜炎常是对称性的双侧。?偏瘫患者发生类风湿关节炎，一般不累及偏瘫侧肢体;骨关节病和痛风首先发生于偏瘫患者的非偏瘫侧关[2]节。?关节疾病的发作与加重，常继发于某些精神因素:如心灵创伤、焦虑或压抑后[3]。以上症状明，神经系统在肢体关节疾病的发生、发展和预后中起着十分重要的作用。由此可以推断，神经免疫系统在颞下颌关节紊乱病中也将起着十分重要的作用。 一、 颞下颌关节区的神经和神经感受器 1、颞下颌关节区的神经来源 哺乳动物的颞下颌关节的发育源于胚胎时期的第一鳃弓，它的神经支配来自第五对 [4]脑神经——三叉神经的分支。1992年，Chen等用辣根过氧化物酶(horseradish peroxidase HRP)逆行追踪技术对鼠的颞下颌关节进行研究时发现，注入关节腔的HRP被逆行转运至同侧的三叉神经节，大量的HRP标记细胞集中在此神经节后部的背外侧份[5]。1995年，Kido等用麦胚凝集素-辣根过氧化物酶(wheat germ agglutinin-horseradish peroxidase WGA-HRP)顺行追踪技术研究鼠颞下颌关节发现，在三叉神经节内注入WGA-HRP后，在同侧的关节囊和关节盘的盘周附着均发现有HRP标 [6]记的神经纤维。以后，Casatti、Hathaway和Yoshino等又分别用不同的试剂对不同 [7][8][9][10][11][12]动物的颞下颌关节进行研究，都取得了同样的结果。大量研究表明 ，颞下颌关节的神经支配主要来自三叉神经下颌支中的耳颞神经、嚼肌神经、颞深神经和翼外肌神经的关节支:颞深神经自下颌神经前表面发出后,行至颧突后分出一支至关节囊的前部、前内侧份和内侧区，然后进入颞肌深面;嚼肌神经自下颌神经前表面发出后，向前外行走于翼外肌深面，分出一支至关节囊前部的外侧份后，在颞肌与颞下颌关节之间跨越下颌切迹至嚼肌深面;耳颞神经自下颌神经后面发出，沿翼外肌深面向后，绕髁状突颈的内侧至其后方后，发出分支到达关节囊的后部、后内侧和外侧区，以及外侧的关节韧带和双板区，并有分支穿过下颌升支支配外侧的骨膜;翼外肌神经随翼外肌进入关节囊，并分布于关节囊的内侧和前内侧区。 in southwest of Zhejiang Provincial Committee of the party's struggle, develop democratic United Front against Japan, established the armed forces and the anti-Japanese base area, decided to establish the CPC Zhejiang Committee. In February 1939, with Gu Yuliang, Secretary Zhu, as Minister, Jie Xu into a propaganda Minister, Zhang Zhihua as women's Minister, Huang yan as youth Minister, zhexi recorder of Penrhyn as military Secretary of the establishment. Hanchang organization attached to the recorders of the West. After the Spring Festival, Zhu Xi was determined to rally, led by Wang Hesong more than more than 100 people, with "first Road South into the team headquarters the name of" back from Wuzhen to Wujiang yan ... Is month, established the Tomb area 1th branch-East water Hong Kong Branch, Branch Secretary Shen Yingjie. Is autumn, the Kuomintang Zhejiang Provincial Government in Southwest Bureau to intensify its anti-communist, ordered political team training in tianmu mountain, is intended to eliminate in the political power of the Communist Party, thorough restructuring of the province's political team to make it become a tool of anti-Communist. In view of this situation, recorder of the West direction West open mass work has been difficult, political signs should not be used, only all go underground, the party's work to continue. To do this, take appropriate measures by a party organization, party members in the Organization of political withdrawal, transfer or make public career as cover, into a secret struggle. In November, Yang and the victory of the battle of the 2、颞下颌关节区的神经分布 [11][13] Dreessen和Keller分别对鼠、猴的颞下颌关节的神经研究中发现，神经分布密 [14]度最大的区域，在关节囊的后部及后外侧部。而Kido等用免疫组化方法则发现神经结构分布密度最大的区域，在鼠关节囊的前外侧部。尽管物种的不同可能造成研究结果上存在一定的差异，但不可否认的是:研究手段的不同可能是造成上述差异的最重要的因 [15]素。例如Tahmasebi等用金氯染色观察绵羊颞下颌关节神经纤维分布时发现，最大密度在关节后部;而用CGRP染色观察感觉神经纤维时，见它们集中于关节囊前部的滑膜和滑膜下层组织内。由此可以推断，Kido的研究可能是仅仅针对感觉神经而言(SP或CGRP包含纤维)，并未对自主神经纤维(NPY和VIP包含纤维)进行研究，所以只能算是对关节神经分布的部分研究。因为尽管免疫活性反应可以追踪到一些神经纤维，但大多数神 [10]经纤维并未被发现。Sarvestani对山羊颞下颌关节用金氯染色的研究证明，最大密度的神经结构(神经纤维和神经末梢)位于关节囊的后部和外侧部分。这种分布可能反映了这些区域对于关节的位置觉、知觉以及在有规律地进行正常的牙合运动中，避免关节过 [16]度运动是相对重要的。现在对颞下颌关节研究的方法很多，但他们大都未能提供准确而全面的分析。金氯染色技术可以展现神经感受器、游离神经纤维及其末梢和免疫活性神经纤维，相对于免疫活性反应来说，金氯染色技术对颞下颌关节神经结构分布的展现要更加全面。 3、颞下颌关节区的神经感受器 颞下颌关节区的神经感受器都是具有不同行为特征的机械感受器，主要分为四类:?型为鲁非尼末梢(Ruffini engings)，?型为帕西尼小体(Pacinian corpuscles)，? [17]型为高尔基腱器官(Golgi -tendon organs)，?型为游离神经末梢。在上述四种类型的感受器中，前三种具有神经被膜，又称小体末梢，先后在鼠、兔、荷兰猪、猫和猴等 [18][19][20]的颞下颌关节中被发现。根据众多学者的研究，我们可以得出区分这四种感受器 [20][13][21][22][23]的标准:?型感受器为小的球形、卵圆形或梭形小体，是低阈慢适应感受器，可对关节的静息位、关节内压变化和关节运动的方向、张力和速度起反应，它主要分布于关节囊的后部、后外侧和前部的表浅部位，在数量上超过其它三种感受器。?型感受器呈圆锥形，并有厚的包膜，为低阈快适应感受器，在静息状态下不兴奋，对关节囊上突发的受力变化起反应，主要位于关节囊的深部和后脂垫。?、?型感受器主要与运动感受有关。?型感受器包膜较薄，呈螺旋形，是最大的关节末梢感受器，为高阈慢适应感受器，冲动传入快，但对频繁冲动适应缓慢，在静息状态下完全不兴奋，通常分布于 career as cover, into a secret struggle. In November, Yang and the victory of the battle of the ropriate measures by a party organization, party members in the Organization of political withdrawal, transfer or make publicshould not be used, only all go underground, the party's work to continue. To do this, take appCommunist. In view of this situation, recorder of the West direction West open mass work has been difficult, political signs -am to make it become a tool of antist Party, thorough restructuring of the province's political tecommunist, ordered political team training in tianmu mountain, is intended to eliminate in the political power of the Communi-ang Provincial Government in Southwest Bureau to intensify its antiEast water Hong Kong Branch, Branch Secretary Shen Yingjie. Is autumn, the Kuomintang Zheji-h, established the Tomb area 1th branche than 100 people, with "first Road South into the team headquarters the name of" back from Wuzhen to Wujiang yan ... Is montn morattached to the recorders of the West. After the Spring Festival, Zhu Xi was determined to rally, led by Wang Hesong more tha ter, Huang yan as youth Minister, zhexi recorder of Penrhyn as military Secretary of the establishment. Hanchang organizationister, Jie Xu into a propaganda Minister, Zhang Zhihua as women's MinisJapanese base area, decided to establish the CPC Zhejiang Committee. In February 1939, with Gu Yuliang, Secretary Zhu, as Min-nt against Japan, established the armed forces and the antiin southwest of Zhejiang Provincial Committee of the party's struggle, develop democratic United Fro2 韧带和关节的半月板，与张力感受有关。 颞下颌关节的关节盘也包含了所有以上三种小体型末梢，但它们仅位于外周的盘附着区，其中前区的密度高于后区，盘中央不含有任 [20][22][24][25][8][25][26]何神经末梢。尽管不少研究已证实，游离神经末梢位于滑膜以及关节盘的外周部位，但没有关于小体型末梢在颞下颌关节滑膜上存在的报道。另外，在颞下颌关节所有部分中，关节囊区、关节囊与关节盘的结合部是小体型感受器分布的最密集区[10]。由此看来，关节囊外侧和关节囊与关节盘的结合部，在感受颞下颌关节静态和动态 [19]过程中扮演了重要角色。 Kawamura等发现关节囊内85个帕西尼小体在关节开放时(35个)及关节关闭时(50个)被牵拉。 ?型感受器为无细胞体末梢，包括有髓鞘的A纤维和无髓鞘的C纤维，以神经丛δ 的形式遍布整个纤维关节囊、后脂垫、关节韧带以及关节血管壁。在对山羊的颞下颌关节研究中发现:?型感受器在关节囊、关节囊与关节盘的结合部、滑膜以及关节盘的外 [8]周均有存在。而对猫的颞下颌关节观察发现，游离神经末梢比较稀少，且大多局限于 [27][28]关节韧带。Haeuchi等观察到人关节盘的后部和外部与关节囊结合处有丰富的游离神经纤维存在。之所以出现上述分布密度的差异，可能与某些学者将网状的?型神经末梢与所谓的真正游离神经末梢区别开来所致。游离神经末梢为痛觉感受器，在正常情况下不发生兴奋，只对直接的化学、温度以及机械的伤害性刺激起反应。它们扮演了伤害 [11][29]性感受器的角色，但同时也可能具有机械感受功能。 二、 颞下颌关节区的神经纤维 1、自主神经纤维的分布和分泌免疫物质功能 研究中发现，在关节囊、滑膜以及关节盘中均有自主神经纤维，且滑膜中主要为自 [30]主神经支配。Widenfalk等应用逆行追踪技术发现:鼠颞下颌关节中大量交感神经传 [31]出纤维源自颈上神经节。Uddman等用同法对鼠颞下颌关节研究发现:在颈上节、星状神经节和蝶腭神经节有大量交感神经细胞体，而在耳神经节有大量的副交感神经细胞体 [8]存在。1999年，Casatti等再次用逆行追踪技术研究鼠颞下颌关节，肯定了上述两人的研究结果，从而证实了颞下颌关节中的自主神经起源于以上的神经节。Casatti等通过研究还发现，自主神经纤维中来自耳神经节的一支进入关节囊内侧。他推断来自颈内动脉壁交感神经丛的交感神经纤维加入到耳神经节，自主神经纤维特异性地在动脉壁上形成神经丛并伴随小动脉和毛细血管进入关节囊。此外，自主神经纤维也在滑膜内小血管上形成神经丛。 自主神经通过分泌神经肽参与了颞下颌关节紊乱病(TMD)的疾病进程。自主神经 Yang and the victory of the battle of the mber,members in the Organization of political withdrawal, transfer or make public career as cover, into a secret struggle. In Nove , only all go underground, the party's work to continue. To do this, take appropriate measures by a party organization, partyshould not be usedCommunist. In view of this situation, recorder of the West direction West open mass work has been difficult, political signs -of the Communist Party, thorough restructuring of the province's political team to make it become a tool of anticommunist, ordered political team training in tianmu mountain, is intended to eliminate in the political power -intensify its anti g Kong Branch, Branch Secretary Shen Yingjie. Is autumn, the Kuomintang Zhejiang Provincial Government in Southwest Bureau toEast water Hon-he team headquarters the name of" back from Wuzhen to Wujiang yan ... Is month, established the Tomb area 1th branchng Festival, Zhu Xi was determined to rally, led by Wang Hesong more than more than 100 people, with "first Road South into tSpri of Penrhyn as military Secretary of the establishment. Hanchang organization attached to the recorders of the West. After the as Minister, Jie Xu into a propaganda Minister, Zhang Zhihua as women's Minister, Huang yan as youth Minister, zhexi recorderJapanese base area, decided to establish the CPC Zhejiang Committee. In February 1939, with Gu Yuliang, Secretary Zhu, -nd the antig Provincial Committee of the party's struggle, develop democratic United Front against Japan, established the armed forces ain southwest of Zhejian3 纤维可分泌神经肽Y(neuropeptide Y，NPY)和血管活性肠肽(vasoactive intestinal peptide，VIP)等神经肽等。实验表明，NPY在颞下颌关节炎的滑液中浓度明显升高，并有较强的钙依赖性非肾上腺素能的血管收缩活性;另外，NPY还具有抑制肾上腺素(NA) [32][33]的作用。VIP则通过分布于动脉壁上的VIP阳性纤维发挥强烈的促小动脉舒张作用; [34]VIP还是骨吸收的刺激因子，Hohmemn发现它通过PGE独立的方式刺激骨吸收。Yoshino[9]等研究了猫颞下颌关节的神经来源后认为:交感神经与颞下颌关节病引起的各种疼痛或者神经病性疼痛有关。许多学者认为:自颞下颌关节输入的感受伤害的信号，能调整 [35][36]交感、副交感传出神经的活动，而后者具有调整血管舒缩功能的作用。 2、感觉神经纤维的分布和分泌免疫物质功能 由于P物质(substance P，SP)与降钙素基因相关肽(calcitonin gene-related peptide，CGRP)大部分存在于初级感觉神经元中，故属于感觉神经肽。SP是伤害性传 [26]入纤维的兴奋性神经介质，与CGRP常共存于同一感觉神经或单独存在于感觉神经中。在病理刺激下，SP不仅顺行传入中枢表达痛觉信息等，而且从神经末梢被逆行释放于局 [37]部组织中，引起无菌性炎症反应。SP又是一种强的血管扩张剂和致水肿因子，能引起局部充血、水肿和炎细胞浸润。CGRP有强烈的扩血管作用，可以增加局部血流量，促进炎症愈合;同时，CGRP是SP分解的有效抑制剂，伴随SP释放的CGRP直接或间接地帮 [36]助SP发挥作用;CGRP还作为感觉神经兴奋性递质，参与疼痛等感觉信息的传入。 [18]Johansson等研究了猴的颞下颌关节后提出:SP能直接影响到炎症的特点并在急、慢 [25]性疼痛中发挥十分重要的作用。而Kido更是认为SP和CGRP在滑膜细胞的摄粒作用中、在调节滑膜下血流以及在颞下颌关节感受伤害的机制和炎性反应的调节中，起着重要的作用。上述研究表明，这两种神经肽在颞下颌关节炎的发生和发展中起到了十分重要的作用。因此，近年来对颞下颌关节感觉神经纤维的研究，多通过研究SP和CGRP阳性纤 [25]维来进行。Kido等用神经示踪技术发现SP和CGRP阳性纤维主要分布在关节囊、盘周附着、滑膜层及骨膜，而密度分布最大的部位为关节囊和关节盘，其中以后外侧为密度最大，但在关节盘中部未见有阳性纤维。他们同时还发现，阳性纤维分布于关节囊和关节盘的血管周围及滑膜中，此两种纤维止于滑膜下层，有部分纤维经由滑膜下层到达滑 [15][6]膜，其终末端接近关节腔。Tahmasebi等对绵羊颞下颌关节的研究、Kido等对鼠颞 [37]下颌关节的研究以及刘向辉等对鼠颞下颌关节的研究，都证实了上述观点。刘向辉还发现有阳性神经纤维末梢终止于滑膜皱襞和指状突起中。Keller也曾经报道猴颞下颌关节内极少量的神经纤维到达关节囊滑膜绒毛部位，与滑膜细胞相接触，多数神经末梢位 should not be used, only all go underground, the party's work to continue. To do this, take appCommunist. In view of this situation, recorder of the West direction West open mass work has been difficult, political signs -am to make it become a tool of antist Party, thorough restructuring of the province's political tecommunist, ordered political team training in tianmu mountain, is intended to eliminate in the political power of the Communi-ang Provincial Government in Southwest Bureau to intensify its antiEast water Hong Kong Branch, Branch Secretary Shen Yingjie. Is autumn, the Kuomintang Zheji-h, established the Tomb area 1th branche than 100 people, with "first Road South into the team headquarters the name of" back from Wuzhen to Wujiang yan ... Is montn morattached to the recorders of the West. After the Spring Festival, Zhu Xi was determined to rally, led by Wang Hesong more tha ter, Huang yan as youth Minister, zhexi recorder of Penrhyn as military Secretary of the establishment. Hanchang organizationister, Jie Xu into a propaganda Minister, Zhang Zhihua as women's MinisJapanese base area, decided to establish the CPC Zhejiang Committee. In February 1939, with Gu Yuliang, Secretary Zhu, as Min-nt against Japan, established the armed forces and the antiin southwest of Zhejiang Provincial Committee of the party's struggle, develop democratic United Frocareer as cover, into a secret struggle. In November, Yang and the victory of the battle of the ropriate measures by a party organization, party members in the Organization of political withdrawal, transfer or make public4 于滑膜下层。但关于滑膜及关节盘内有无感觉神经纤维分布仍存在争议。如Johansson [18][38]等对猴颞下颌关节的研究中，并未发现阳性纤维位于关节盘及滑膜层。刘静等用PAP 法研究猫颞下颌关节中SP阳性纤维的分布也得出相似结论。之所以出现上述争议，分析 认为可能是后者将颞下颌关节软组织分别取出制成标本，从而难以对颞下颌关节整体结 构、特别是血管周围及关节盘中SP阳性纤维的分布情况进行研究有关。 以上研究说明，感觉神经在颞下颌关节紊乱病中不单具有感觉功能，而且有直接 或间接的神经调节分泌免疫物质作用。 三、意义: 通过对颞下颌关节神经结构及其分布的观察，可以从神经因素方面进一步研究颞下 颌关节紊乱病的发病机理，再结合颞下颌关节疾病的临床表现，探讨神经分布与颞下颌 关节运动和功能之间存在的相互关系，从而为进一步明确颞下颌关节的发病机制、乃至 为疾病的诊断和治疗提供理论上的依据。 参 考 文 献 1.马绪臣主编。颞下颌关节病的基础与临床。第一版，北京:人民卫生出版社，2000， 39-59。 2.Marshall KW, Chill B, Inman RD. Substance P and arthritis:analysis of plasma and synovial fluid levels. Arthritis Rheum.1990;33(1):87-92 3.Martin L, Dennis AC, John H. Science. 1987;235(4786):393-397 4.Mckay GS, Yemm R, Cadden SW. Br Deng J. 1992;173(2):127-132 5.Chen TT, Turner DF. Temporomandibular joint innervation in rats: a horseradish peroxidase study. 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In view of this situation, recorder of the West direction West open mass work has been difficult, political signs -of the Communist Party, thorough restructuring of the province's political team to make it become a tool of anticommunist, ordered political team training in tianmu mountain, is intended to eliminate in the political power -intensify its anti g Kong Branch, Branch Secretary Shen Yingjie. Is autumn, the Kuomintang Zhejiang Provincial Government in Southwest Bureau toEast water Hon-he team headquarters the name of" back from Wuzhen to Wujiang yan ... Is month, established the Tomb area 1th branchng Festival, Zhu Xi was determined to rally, led by Wang Hesong more than more than 100 people, with "first Road South into tSpri of Penrhyn as military Secretary of the establishment. Hanchang organization attached to the recorders of the West. After the as Minister, Jie Xu into a propaganda Minister, Zhang Zhihua as women's Minister, Huang yan as youth Minister, zhexi recorderJapanese base area, decided to establish the CPC Zhejiang Committee. In February 1939, with Gu Yuliang, Secretary Zhu, -nd the antig Provincial Committee of the party's struggle, develop democratic United Front against Japan, established the armed forces ain southwest of ZhejianYang and the victory of the battle of the mber,members in the Organization of political withdrawal, transfer or make public career as cover, into a secret struggle. In Nove , only all go underground, the party's work to continue. To do this, take appropriate measures by a party organization, party5 in the caudal brainstem of the rat following noxious chemicalstimulation of the TMJ. J Comp Neurol. 1995;356(3):444-456 9.Yoshino K, Kawagishi S, Amano N. Morphological character ristics of primary sensory and post-synaptic sympathyetic neurons supplying the TMJ in the cat. 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In view of this situation, recorder of the West direction West open mass work has been difficult, political signs -of the Communist Party, thorough restructuring of the province's political team to make it become a tool of anticommunist, ordered political team training in tianmu mountain, is intended to eliminate in the political power -intensify its anti g Kong Branch, Branch Secretary Shen Yingjie. Is autumn, the Kuomintang Zhejiang Provincial Government in Southwest Bureau toEast water Hon-he team headquarters the name of" back from Wuzhen to Wujiang yan ... Is month, established the Tomb area 1th branchng Festival, Zhu Xi was determined to rally, led by Wang Hesong more than more than 100 people, with "first Road South into tSpri of Penrhyn as military Secretary of the establishment. Hanchang organization attached to the recorders of the West. After the as Minister, Jie Xu into a propaganda Minister, Zhang Zhihua as women's Minister, Huang yan as youth Minister, zhexi recorderJapanese base area, decided to establish the CPC Zhejiang Committee. In February 1939, with Gu Yuliang, Secretary Zhu, -nd the antig Provincial Committee of the party's struggle, develop democratic United Front against Japan, established the armed forces ain southwest of ZhejianYang and the victory of the battle of the mber,members in the Organization of political withdrawal, transfer or make public career as cover, into a secret struggle. In Nove , only all go underground, the party's work to continue. To do this, take appropriate measures by a party organization, partyshould not be used7