小关节源性腰痛的基础及临床研究

第四军医大学博士学位论文

类号分

级密

国际进类号十分（UDC ）

第四军医大学

学 位 论 文

小关节源性腰痛的基础及临床研究

题题（名和副名）

龚 凯 （作者姓名）

导教师指姓名罗卓荆 教授（主任医师）

导教师单指位第四军医大学西京医院骨科

请学级别申位博士

专业称名外科学（骨外） 论文提交日期2010.04 辩答日期2010.05 论时间文起止2007 年 8 月至 2010 年 3 月

学单位授予位第四军医大学

第四军医大学博士学位论文

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第四军医大学博士学位论文

小关节源性腰痛的基础及临床研究

研 究 生：龚 凯

学科专业：外科学（骨外）

所在单位：第四军医大学西京医院骨科

导师：罗卓荆教授（主任医师）

辅导教师：

资助基金项目：

关键词：P物质，下腰痛，腰椎小关节骨性关节炎，疼痛模型，腰椎小关节滑膜囊肿，峡部裂性滑脱

中国人民解放军第四军医大学

2010年5

第四军医大学博士学位论文

目录

缩略语表 (1)

中文摘要 (3)

ABSTRACT (8)

前 言 (15)

文献回顾 (17)

第一部分 SD大鼠腰椎小关节源性疼痛模型的建立及相关研究 (38)

实验一、SD大鼠腰椎小关节P能神经纤维分布的初步研究 (38)

实验二、SD大鼠腰椎小关节神经支配的节段分布规律及背根神经节中传入神经元特点的相关研究 (43)

实验三、单关节腔内注射弗氏佐剂诱导大鼠腰椎小关节炎性疼痛模型的建立及初步研究 (53)

实验四、单关节腔内注射碘乙酸钠诱导大鼠腰椎小关节骨性关节炎伴疼痛模型的建立及初步研究 (70)

第二部分、腰椎小关节滑膜囊肿与出血性滑膜囊肿诊断和治疗的回顾性对比研究..........................................错误！未定义书签。 第三部分、经骶骨椎体间钛笼植入原位融合与复位后经椎间孔椎体间自体髂骨融合治疗腰骶部2度峡部裂性滑脱疗效的对比研究. (95)

小 结 (106)

参考文献 (108)

个人简历和研究成果 (135)

致 谢 (137)

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第四军医大学博士学位论文

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缩略语表

缩略词 英文全称 中文全称 SP substance P P 物质

ABC avidin-biotin comeplex

卵白素-生物素复合物 DAB 3,3'-diaminobenzidine

3,3-四盐酸二胺基联

苯胺

PFA paraformaldehyde

多聚甲醛 EDTA ethylenediamine tetraacetic acid 乙二胺四乙酸 FBS fetal bovine serum

胎牛血清

EDTA Na2 ethylene diamine tetraacetic acid disodium 乙二胺四乙酸二钠

FB fast blue 快蓝 NY nuclear yellow 核黄

FITC fluorescein isothiocyanate 异硫氰酸荧光素 CFA complete freund's adjuvant 弗氏完全佐剂 IL-1β

interleukin 1

白介素1-β IL-6 interleukin-6 白介素6 TNF-α

tumor necrosis factor-α

肿瘤坏死因子α

第四军医大学博士学位论文

-2-TB toluidine blue

甲苯胺蓝 PWT paw withdrawal threshold

缩抓阈值 MH mechanical hyperalgesia 机械痛敏 TH thermal hyperalgesia

热刺激痛敏 GFAP glial fibrillary acidic protein

神经胶质原纤维酸性蛋白质 MIA monosodium iodoacetate 碘乙酸钠 ATF-3 activating transcription factor -3 转录因子3 OA osteoarthritis

骨性关节炎 LFJ lumbar facet joint

腰椎小关节 LBP low back pain

下腰痛 HSC hemorrhagic synovial cyst 出血性滑膜囊肿 V AS visual analog scale

视觉模拟评分ODI Oswestry disability index Oswestry 功能障碍指数 IS isthmic spondylolisthesis 峡部裂性滑脱 TLIF transforaminal lumbar interbody fusion 经椎间孔椎体间融合 WL whole lumbar lordosis

腰椎前凸角 LSA lumbosacral angle

腰骶角

第四军医大学博士学位论文

小关节源性腰痛的基础及临床研究

博士研究生： 龚 凯

导 师： 罗卓荆 教授

第四军医大学西京医院骨科,西安 710032

中文摘要

下腰痛是指一组以腰骶部、骶髂、臀部疼痛为主要症状的综合症，可伴有下肢放射痛，麻木及无力等其他症状。国外的研究表明正常人群中约有60%-80%的成人在日常生活中有过一次及以上的下腰痛经历。在欧美国家下腰痛是45岁以下人群最常见的致残原因，随着人口老年化的进程其发病率还在逐年上升。在国内，下腰痛是骨科、运动康复医学及疼痛诊疗最常见的疾患，占日常门诊量的1/3; 是仅次于上呼吸道感染而就诊的第二位常见原因。现今下腰痛已不再是单纯的医学问题，而是能引发一系列心理及社会经济负担的复杂难题。Waddell指出“医学的发展并没有解决下腰痛问题，甚至使其恶化，下腰痛是20世纪医疗卫生的灾难和未解之谜团”。

下腰痛的产生是多因素的。以往关于下腰痛的研究主要集中在椎间盘源性疼痛。然而随着研究的深入，腰椎小关节疾病引起的疼痛逐渐引起人们的重视。本课题拟通过单关节腔内注射完全弗氏佐剂及碘乙酸钠建立腰椎小关节源性疼痛动物模型，初步探讨腰椎小关节源性疼痛的相关机制，为进一部

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第四军医大学博士学位论文

研究腰椎小关节源性疼痛的机制及相关治疗提供实验平台，此外本课题还针对两种导致下腰痛的腰椎小关节疾病进行长期随访回顾性对比研究，以期能更好的了解腰椎小关节病变所致下腰痛的临床特点及治疗方法。

第一部分 SD大鼠腰椎小关节源性疼痛模型的建立及相关研究 1.SD大鼠腰椎小关节P能神经纤维分布的初步研究

目的：探讨P能神经纤维在SD大鼠腰椎小关节各组织结构中分布情况。方法： 采用病理切片及免疫组织化学染色的方法研究P能神经纤维在SD大鼠腰椎小关节关节软骨，滑膜皱襞及软骨下骨中的分布情况。结果：P物质染色阳性神经纤维免疫染色呈迂曲条索状无髓纤维，直径1-5μm，在大鼠腰椎小关节关节囊，滑膜皱襞，软骨下骨及骨髓腔内均有分布，其中以关节囊分布密度较大。结论： P能神经纤维在SD大鼠腰椎小关节各组织结构中均有分布，是腰椎小关节源性疼痛来源的解剖学基础。

2.SD大鼠腰椎小关节感觉传入纤维节段分布及传入神经元特点的相关研究

目的：研究SD大鼠腰椎小关节感觉传入纤维节段分布规律及背根神经节中相应初级感觉传入神经元形态学及功能特点。方法：采用快蓝逆行标记SD 大鼠同侧各节段背根神经节中腰椎小关节感觉传入神经元的节段分布规律，通过复合核黄逆行标记及P物质免疫荧光染色等双标的方法研究腰椎小关节初级感觉神经元的分支分布及功能特点。结果：SD大鼠腰5/6关节接受腰1至5节段支配，其中又以腰3至腰5节段支配为主；感觉传入神经元以中小型神经元为主，各节段背根节中均存在P物质/快蓝双标神经元，少量腰椎小关节初级感觉传入神经元有分支支配同侧下肢足底感觉。结论：SD大鼠接受多节段神经纤维支配，及其初级感觉传入神经元的形态学及功能特点可能造成是腰椎小关节源性腰痛及下肢牵涉痛的解剖基础。

3.关节腔内注射弗氏佐剂诱导SD大鼠腰椎小关节炎性疼痛模型的建立

目的：建立SD大鼠腰椎小关节炎性疼痛模型并对其疼痛机制进行初步研

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第四军医大学博士学位论文

究。方法：采用单关节腔内显微注射完全弗氏佐剂诱导建立SD大鼠腰椎小关节炎性疼痛模型后，测量术后不同时间点大鼠同侧肢体足底机械痛及辐射热痛阈值变化，对关节软骨退变程度及滑膜炎性反应进行评估，测量背根神经节P物质含量、脊髓中P物质及GFAP含量变化情况，并观察塞来考昔对大鼠术后机械痛阈的影响。结果：单关节腔内注射完全弗氏佐剂后，大鼠关节软骨出现轻微度退变，滑膜炎性反应持续较长时间，术后直接测量并观察到大鼠同侧肢体足底机械痛及辐射热痛阈值出现降低，脊髓及背根节中P物质含量上升，脊髓背角星形胶质细胞增多，而塞来考昔术后可有效抑制术后大鼠机械痛阈变化。结论：利用关节腔内注射完全弗氏佐剂可成功诱导大鼠单关节炎性疼痛模型，疼痛产生的机制可能与滑膜炎性反应有关。

4.关节腔内注射碘乙酸钠诱导大鼠腰椎小关节骨性关节炎伴疼痛模型的建

立

目的：建立SD大鼠腰椎小关节骨性关节炎伴疼痛模型并对其疼痛机制进行初步探讨。方法：采用单关节腔内显微注射不同浓度碘乙酸钠诱导建立SD 大鼠腰椎小关节骨性关节炎模型后，测量术后不同时间点大鼠同侧肢体足底机械痛及辐射热痛阈值变化，对关节软骨退变程度行染色评估。依据术后疼痛行为学变化及软骨退变情况选择碘乙酸钠最适造模浓度。与术后不同时间点性关节及滑膜HE染色，采用ELSIA法测定术后滑膜炎性因子含量变化，免疫荧光染色计数背根神经节中P物质阳性细胞及ATF-3阳性细胞，并观察塞来考昔与加巴喷丁对大鼠术后机械痛阈的影响。结果：关节腔内注射碘乙酸钠后，大鼠关节出现明显骨性关节样病理改变，并随时间推移逐步加重。选取最适造模浓度为碘乙酸钠0.1mg/5μL。术后滑膜出现短暂性炎症反应，与早期术后机械痛及热痛阈值变化规律吻合，晚期关节结构出现明显破坏，软骨下骨暴露，伴随有机械痛及热痛阈值持续下降，各时间点背根节P物质变化规律与疼痛阈值变化规律吻合，背根节中早期无明显ATF-3表达，晚期其表达增加，抗炎药物早期镇痛效应明显，中晚期失效，加巴喷丁不同时间

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第四军医大学博士学位论文

点镇痛效应均存在。结论：采用关节腔内注射碘乙酸钠可成功诱导大鼠腰椎小关节骨性关节炎伴疼痛模型，疼痛产生的机制可能有炎性因素及关节结构因素共同参与。

第二部分、腰椎小关节滑膜囊肿与出血性滑膜囊肿诊疗的回顾性对比研究

目的：探讨两种腰椎小关节囊肿的流行病学资料，临床表现及手术疗效的不同特点。方法： 通过长期随访及回顾性分析，对比研究我科住院治疗的18例腰椎小关节滑膜囊肿及5例腰椎小关节出血性滑膜囊肿患者的流行病学资料，临床表现及手术疗效。结果：与腰椎滑膜囊肿相比，腰椎出血性滑膜囊肿平均发病年龄低，病程短，多有诱发因素，下肢放射痛症状严重，保守治疗通常无效；但两组患者在性别比，病变部位及伴随病变等方面无明显差异。两组患者经椎板开窗减压，囊肿切除，囊肿侧关节突关节内侧1/3切除术治疗后术前疼痛明显缓解，疗效满意，术后并发症发生率低，无腰椎不稳及复发报道。结论：腰椎出血性滑膜囊肿有其特定的临床表现，手术切除是针对腰椎小关节滑膜囊肿与出血性滑膜囊肿的安全有效治疗手段。

第三部分、经骶骨椎体间钛笼植入原位融合与复位后经椎间孔椎体间自体髂骨融合治疗腰骶部Ⅱ度峡部裂性滑脱疗效的对比研究 目的：对经骶骨椎体间钛笼植入原位融合与复位后经椎间孔椎体间自体髂骨融合两种不同术式治疗腰骶部Ⅱ度峡部裂性滑脱的疗效进行对比研究。方法：依据手术方式不同将34例患者分为两组，A组采用术式为后路减压复位，经椎间孔椎体间自体髂骨移植及后路短节段固定，共21例，B组采用术式为后路减压，经骶骨椎体间钛笼植入原位融合组及后路短节段固定，共13例。疗效评价指标包括：手术时间、术中出血，住院天数，术前术后腰腿痛VAS评分、ODI评分

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第四军医大学博士学位论文

变化。影像学评价指标包括：骨性融合率，滑脱复位及丢失率，腰椎前凸角及腰骶角度数变化。结果：B组术式手术时间及术中出血少于A组。骨性融合率A组为95.2%，B组为93.2%。两组患者术后原有症状均得到明显改善，腰腿痛VAS评分及ODI评分明显降低，术前及术后腰椎前凸角及腰骶角较术前增加，但组间比较均无明显统计学差异。 A组共3例患者出现术后并发症，其中2例供骨区疼痛，1例表浅感染，1例术后6月出现螺钉松动；B组共5例患者出现手术并发症，其中术中硬脊膜撕裂2例，术后一过性骶1神经根感觉障碍2例，短暂性踇长伸肌无力1例。结论：针对椎间隙明显塌陷并骨质疏松的腰骶椎峡部裂滑脱患者，经骶骨椎体间钛笼植入原位融合也是以一种可供选择的有效治疗手段。其中期疗效堪比TLIF术式，但神经功能损害并发症发生率相对略高。

关键词： P物质，下腰痛，腰椎小关节骨性关节炎，疼痛模型，腰椎小关节滑膜囊肿，峡部裂性滑脱

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第四军医大学博士学位论文

The basic and clinical research on the low back pain of

lumbar facet joint relative diseases

Candidate for doctor: Gong Kai

Supervisor: Prof. Luo Zhuojing

Department of orthopedics, Xi Jing hospital, Fourth Military Medical

University, Xi’an 710032, China

Abstract

Low back pain was defined as a pain syndrome mainly located at lumbosacral

area and buttocks, with or without weakness and radiating pain on the legs. The result of America and Europe researchers’ studies show that about 60% to 80% of adult patients would be suffered form low back pain for at least one time during their whole life-time. In fact, low back pain was considered as the common cause of disability among patient under 45 years old. In addition, .its incidence is still rising year on year complied with the population aging process. In China, about 1 / 3 outpatients come for their low back pain generally. Low back pain is the most common disorder of orthopedic, sports medicine and pain rehabilitation and the second common cause for visit, which is only second to upper respiratory tract infection. Currently, low back pain is not only a pure medical problem, but also a complex problem which may lead to a series of psychological and socio-economic burdens. Waddell says that "the development of modern medicine did not solve the problem of low back pain and even made it worse than

before. Low back pain is a disaster and unsolved mystery in twentieth century

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第四军医大学博士学位论文

health care.

The generation of low back pain is influenced by a variety of factors. Previous studies about low back pain are mainly focused on the discogenic pain. However, lumbar facet joint was proven to be a important pain generator. Recently, the low back pain derived from lumbar facet joint gradually arouses our attention. In the present study, we’d like to established two facet joint pain animal models though intra-articular injection of complete freund's adjuvant or monosodium iodoacetate, and study about the pathological and functional characteristics of this two new models. Based on the animal model, we make a preliminary study on the mechanisms of lumbar facet joint pain. The new animal models would be used as a helpful tool for the further studies. In addition, we also make some retrospective studies on the diagnosis and outcome of two low back pain-relative lumbar facet joint diseases in order to make sure the clinical feature of lumbar facet joint pain and its treatment.

Part Ⅰ. Establishment of the rat model of lumbar facet joint pain and relative study

1.The distribution of substance P positive nerve fiber in the SD rat lumbar facet joint Objective: Study about the distribution of substance P positive nerve fiber in the SD rat lumbar facet joint. Method: Immunohistochemical staining on the pathological section of SD rat lumbat facet joint was used to the distribution of substance P positive nerve fiber in articular cartilage, plica synovialis and subchondral bone. Results: Substance P positive nerve fibers were found in articular cartilage, plica synovialis and subchondral bone. The nerve fibers were tortuous cord-like non-myelinated fibers with a diameter range from 1 to 5 μm. Compared to the two other structures, the density of nerve fibers was relative high in the joint capsule. Conclusion: Substance P positive nerve fibers can be

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第四军医大学博士学位论文

found in articular cartilage, plica synovialis and subchondral bone. It may be the anatomical basis of lumbar facet joint pain.

2. The study on the segment distribution pattern of lumbar facet joint innervated nerve fibers and the morphological feature of primary afferent sensory neurons

Objective: Study about the segment distribution pattern of lumbar facet joint innervated nerve fibers and the morphological feature of primary afferent sensory neurons in the dorsal root gangl ion. Methods: The retrograde transport of fast blue was used to study the segment distribution pattern of lumbar facet joint innervated nerve fibers. Double mark of fast blue and nuclear yellow, or fast blue and substance P (immunofluorescence staining) was used to analysis the morphological and functional feature of primary afferent sensory neurons in the dorsal root ganglion. Results: The SD rat left L5/6 facet joint is innervated by unilateral multi-segment DRGs, including L1 DRG to L5 DRG. The afferent nerve fibers are mainly derived from two or three segments above. Most of the primary afferent sensory neurons are small or medium sized neurons. FB/SP double-labled neurons can be found in each DRG range from L1 to L5. A small amount of lumbar facet joint primary sensory afferent neurons have branches to dominate the ipsilateral lower extremity plantar skin. Conclusion: The fact that the innervation of lumbar facet joint is multi-segmental in SD rat and some primary afferent sensory neurons are FB/NY or FB/SP double-labled, may be the anatomical basis of lumbar facet joint pain and its referred pain.

3. Establishment of the rat facet joint inflammation pain model by intra-articular injection of complete Freund's adjuvant

Objective: To establish a rat facet joint pain model induce by inflammation and make a preliminary study on the pain mechanisms in this model. Methods: A

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第四军医大学博士学位论文

monoarthritis of lumbar facet joint was induced by intra-articular injection of complete Freund's adjuvant. The change of paw withdrawal threshold for thermal hyperalgesia and mechanical hyperalgesia was measured directly on the different postoperative time points. The degeneration of articular cartilage and the extent of synovitis were evaluated by toluidine blue and HE staining, respectively. In addition, the change of substance p mRNA level in L5 DRG and spinal cord and the number of GFAP positive neurons were also recorded. Finally, the pharmacologic of celecoxib on mechanical hyperalgesia were tested on three different postoperative time points. Results: After the injection of CFA, a constant synovitis and mild or moderate degeneration of articular cartilage were found during the whole observation period. Significant decrease of paw withdrawal threshold was directly found after injection while the mRNA level of substance p L5 DRG and spinal cord and number of GFAP positive neurons were increased simultaneously. Celecoxib can effectively inhibit the decrease of PWT on both early and late period. Conclusion: A new rat facet joint inflammation pain model could be successfully established by intra-articluar injection of CFA. We presume the inflammation of synovium may play a role in the generation of pain in this animal model.

4. Establishment of the rat facet joint osteoarthritis pain model by intra-articular injection of monosodium iodoacetate

Objective: To establish a rat facet joint osteoarthritis pain model and make a preliminary study on the mechanisms of facet joint osteoarthritis pain in this model. Methods: Lumbar facet joint osteoarthritis was induced by intra-articular injection with different concentrations of monosodium iodoacetate. The change

of paw withdrawal threshold for thermal hyperalgesia and mechanical hyperalgesia was measured directly on the different postoperative time points.

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第四军医大学博士学位论文

The optimal dosage used for establish osteoarthritis model was selected based on the result of postoperative cartilage degeneration and the change of paw withdrawal threshold. The extent of synovium inflammation was evaluated by HE staining and the contents of three main inflammatory cytokines. The substance P and ATF-3 positive neurons were recorded on different postoperative time point. Finally, the pharmacologic of celecoxib and gabapentin on mechanical hyperalgesia were tested on different postoperative time points. Results: After the injection of MIA, OA-like cartilage degeneration was found in a time –dependent pattern. The optimal concentration MIA used for establish osteoarthritis model is 0.01mg/5μL. A transient synovium inflammation was noted within one week after injection. The change of synovium inflammation and the change of SP positive neurons number were closely track the first phase of pain- related behaviour changes (1-7days). During the late observation period, obvious structure destruction like expose of subchondral bone, bone marrow fibrosis and marginal osteophyte formation were found in consistent with the second decrease of PWT. Significant increase of ATF-3 positive neurons was only found 14 days after injection. Celecoxib was effective only at day 3 and ineffective at day 21 and 56 while gabapentin kept its inhibitory effect at all three time points. Conclusion: A new rat facet joint osteoarthritis pain model could be successfully established by intra-articluar injection of MIA. This model might provide a useful tool for further study to ascertain the complex mechanism of facet joint pain.

Part Ⅱ. A retrospective study of the contrast on the diagnosis, clinical present and treatment outcome of lumbar facet joint hemorrhagic and non- hemorrhagic synovial cyst

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第四军医大学博士学位论文

Objective: To study about the difference on the epidemiology data, clinical present and treatment outcome between the lumbar facet joint hemorrhagic and non- hemorrhagic synovial cyst. Methods: A retrospective review and contrast analysis of clinical relative data on 18 patients with lumbar facet joint synovial cysts and 5 patients with lumbar facet joint hemorrhagic synovial cysts. Results: Compared to non- hemorrhagic synovial cyst, lumbar facet joint hemorrhagic synovial cyst has its own characteristics, including younger age, short course of disease, causative factor, severe radicular pain and resistance to the conservative treatment. However, there is still some come point between both cysts, like sex ratio, predilection site and concomitant local diseases. Hemilaminectomy or laminectomy with medial facetectomy without fusion was carried out on all patients in both groups. The clinical outcome was good and the complications or re-operation rate was low. Conclusion:

Lumbar facet joint hemorrhagic synovial cyst has its own characteristics in clinical epidemiology data and clinical presentation. Surgical treatment for both cysts was safe and effective.

Part Ⅲ. Reduction, transforaminal lumbar interbody fusion (TLIF) with posterior fixation Versus Transsacral cage fusion in situ with posterior fixation in treatment of Grade Ⅱ adult isthmic spondylolisthesis in lumboscacral spine

Objective :To study about the outcome of transsacral cage fusion in situ with in the management of adult lumboscacral Grade Ⅱisthmic spondylolisthesis, and compare it to the TLIF and reduction procedure. Methods: 21 patients in group A were treated by reduction and TLIF, and 13 in group B was treated by transacral cage fusion. ODI score, VAS score of back pain and leg pain were

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第四军医大学博士学位论文

used to evaluate the clinical outcomes. The radiological parameters for assessment included percentage of slippage, whole lumbar lordosis (WL) and lumbosacral angle (LSA). Operative data, fusion rate and perioperative complications were recorded.. Results: The mean operation time and blood loss of group B was less than that of group A. Both two groups obtained good recovery of previous symptoms. The decrease of back pain and leg pain after surgery were significant within each group, but without much difference between the two groups. No significant differences on LSA，WL，V AS and ODI scores were found between the two groups after surgery. Solid fusion was 95.2% in group A and in 92.3% in group B. In group A, two suffered graft site pain, one had superficial infection, and one had screw loosening , while in group B, dural tears were found in two patients, transient S1 paraesthesia in two, and extensor hallucis longus weakness in one. Conclusion: For patients with a collapsed disc space and poor bone quality, posterior in situ transsacral cage fusion might be used as an alternative to TLIF procedure. The short term clinical and radiological outcomes of transsacral cage group were comparable to those of TLIF group, though with a relatively higher neurological complication rate.

Keywords: substance P, low back pain, lumbar facet joint osteoarthritis, pain animal model, lumbar facet joint synovial cyst, isthmic spondylolisthesis

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第四军医大学博士学位论文

前言

下腰痛的存在在人类疾病史上由来已久，是一种非常普遍的疾病。正常人群中下腰痛的发病率约为60-80%[1]。美国疼痛协会的一项研究显示，约84%的成年人一生中有过至少1次下腰痛经历，持续时间超过4周[2]. 而Bressler[3]的研究提示，下腰痛在大于65岁的人群中发病率高于人群整体水平，且在逐年上升趋势。目前下腰痛已成为欧美国家患者就医的第二大主要原因[4], 仅次于上呼吸道感染。而在我国，下腰痛也已成为骨科最常见临床疾患，每年约有2千万患者因下腰痛而就医。下腰痛的反复发作不仅使患者遭受疼痛的反复折磨，而且对机体健康以及运动功能造成极大的影响，严重者甚至可以致残。

随着现代社会的不断发展, 由下腰痛引起的误工、医疗和补偿费用等一系列社会及经济问题正在逐渐浮现。大量调查研究及证据显示[5-6]，下腰痛及其后遗症已对社会的医疗和经济发展形成高额的负担，可以和心脏病，抑郁症和糖尿病等疾病相提并论。英国的一项医疗花费调查结果表明，仅1998年一年由下腰痛造成的直接经济损失达1.6亿英镑[7]，后续的康复治疗费用及误工损失则高达6.6亿到12.3亿英镑。而来自1997年的美国医疗消费支出调查显示，该年度用于下腰痛治疗的直接医疗费用为170亿美元，继发的误工经济损失达到280亿美元[8]。

现今下腰痛的诊断及治疗仍是医学界的一大难题。研究表明局部解剖结构如腰椎间盘，关节突关节，韧带及肌肉组织均有可能是疼痛的来源。在此基础上生物力学因素及创伤、畸形及肿瘤等疾病也能对下腰痛的产生及发展造成影响[9]。 目前国内外学者的主要研究热点集中在椎间盘源性腰痛上。已有结论表明由髓核突出造成的机械压迫及退变间盘中炎性介质局部扩散导致神经根炎症是引起椎间盘源性腰痛的两个主要原因[10-12]。腰椎小关

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第四军医大学博士学位论文

节是脊柱重要后部组成结构，与椎间盘一起构成脊柱的基本运动功能单位 —— 三关节复合体，具有十分重要的生物力学作用。自Ghormley[13]1933年提出“小关节综合症”这一定义以来， 腰椎小关节一直被认为是下腰痛的来源之一。Boswel[14]的研究结果证实： 在排除心理因素影响的条件下，约有15-45%的下腰痛患者疼痛来源于腰椎小关节。然而与椎间盘源性腰痛相比，腰椎小关节源性疼痛的相关研究目前主要集中在临床诊断及疗效评估等方面[15], 未能对其机制进一步深入研究。究其原因，缺乏有效的实验动物模型是其中主要影响因素之一。本课题以腰椎小关节源性疼痛及其相关疾病的研究为切入点，为进一步探讨下腰痛疼痛机制及治疗提供新的思路。

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第四军医大学博士学位论文

文献回顾

一、 腰椎小关节骨性关节炎及疼痛的研究现状

1.腰椎小关节的解剖学研究

腰椎小关节是由相邻节段椎骨的上、下关节突及包绕在外部的关节囊共同构成，左右各一，是腰椎后部结构的重要组成部分。

1.1腰椎小关节关节面

腰椎小关节的关节面由上位椎体的下关节突外侧面与下位椎体的上关节内侧面对合构成，两关节面呈内外侧关系。依据其冠状面形态学特点[16]，将小关节关节面分为三种类型：平坦型，即上下关节突关节面呈直线相互平行关系；C型，即怀抱型，上关节突关节弧形凹面将呈弧形凸面的下关节突关节面怀抱；J型，即反环抱型，下关节突关节环抱上关节突关节，关节间隙类似于“J”，前两种类型较为多见，后者较为少见。 由第一腰椎往下，关节突关节关节面方向由近似矢状位逐渐演变为斜位, 至第五腰椎时几呈冠状位。

1.2 腰椎小关节关节囊

腰椎小关节关节囊主要位于关节的后外侧，厚度约为1mm，附着于关节边缘2mm处[17]。关节囊背侧较薄，在后方由关节突关节副韧带、棘间韧带及后外侧多裂肌肌束加强；前壁较厚，与黄韧带移行融合，参与构成椎管后壁，而上下壁最为松弛，便于小关节活动。腰椎小关节关节囊可分为两层，外层是致密的薄层平行排列纤维组织，内层为类似与黄韧带的弹性纤维，走行不一。关节囊上部及中部纤维由下关节根部及上关节突上部向外侧走行，包绕关节面，关节囊下部纤维经由椎板中下部包绕关节突，止于上关节突基底部[18-19]。

1.3 腰椎小关节滑膜及关节腔

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