The effects of joint immobilization on articular cartilage of the knee in previously exercised rats

Studies have determined the effects of joint immobilization on the articular cartilage of sedentary animals, but we are not aware of any studies reporting the effects of joint immobilization in previously trained animals. The objective of the present study was to determine whether exercise could prevent degeneration of the articular cartilage that accompanies joint immobilization. We used light microscopy to study the thickness, cell density, nuclear size, and collagen density of articular cartilage of the femoral condyle of Wistar rats subjected to aerobic physical activity on an adapted treadmill five times per week. Four groups of Wistar rats were used: a control group (C), an immobilized group (I), an exercised group (E), and an exercised and then immobilized group (EI). The right knee joints from rats in groups I and EI were immobilized at 90 °C of flexion using a plastic cast for 8 weeks. Cartilage thickness decreased significantly in group I (mean, 120.14 ± 15.6 μm, P < 0.05), but not in group EI (mean, 174 ± 2.25), and increased significantly in group E (mean, 289.49 ± 9.15) compared with group C (mean, 239.20 ± 6.25). The same results were obtained for cell density, nuclear size, and collagen density (in all cases, P < 0.05). We concluded that exercise can prevent degenerative changes in femoral articular cartilage caused by immobilization of the knee joint.     

大骨节病关节软骨胶原表型表达和软骨细胞异常分化的研究

目的探讨大骨节病关节软骨胶原表型表达的变化特点和软骨细胞异常分化在发病中的意义。方法用单克隆免疫组化法测定５例大骨节病关节软骨Ⅰ、Ⅱ、Ⅲ、Ⅵ、Ⅹ型胶原表型的表达。结果（１）关节软骨表层的Ⅱ型胶原表型表达减少；（２）Ⅰ、Ⅲ和Ⅵ型胶原表型表达见于关节软骨全层，而Ⅹ型胶原仅限于关节软骨钙化层和深层软骨细胞团周围；（３）软骨细胞团有Ⅰ、Ⅱ、Ⅲ、Ⅵ型胶原表型表达，而软骨细胞坏死区内无任何胶原表型表达。结论大骨节病关节软骨胶原表型表达类似于原发性骨关节病的变化，但在关节软骨表层Ⅰ型胶原表型表达增强以及软骨坏死区内无任何胶原表型表达不同于原发性骨关节病。     

Existence of a neuropathic pain component in patients with osteoarthritis of the knee

Purpose

Pain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA.

Materials and Methods

Ninety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearman''s correlation coefficient by rank test.

Results

Our study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant.

Conclusion

PainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.     

An anatomical study of the muscles that attach to the articular disc of the temporomandibular joint

The masticatory muscles are generally described as the muscles that originate from the cranium and insert on the mandible. Some of the masticatory muscles also insert into the articular disc of the temporomandibular joint. Although there are numerous reports of studies on the attachment of the fibers to the disc, most reports discuss only one muscle. We have shown that the masticatory muscles are not simply a group of clearly independent muscles, but that these muscles contain various transitional muscle bundles among the major muscles. From this point of view, we carried out minute dissection of the collective muscles and muscle bundles surrounding the temporomandibular joint. We dissected 40 head halves of 20 Japanese cadavers (10 males, 10 females: average 79.6 yr). After complete removal of the bony elements, the structures surrounding the temporomandibular joint were investigated en‐block. In all specimens, the superior surface of the upper head of lateral pterygoid and the midmedial muscle bundle were attached to the disc. In some specimens, the discotemporal bundle, zygomaticomandibularis, and masseter were attached to the anterior surface of the disc. The total vector of these muscles pulls the disc anteriorly. In contrast, the vector of the muscles to the condylar processes of the mandible pulls the mandible medially. From these observations, it seems that the fibers, which attach to the disc act to steady the disc against the masticatory movement. Clin. Anat. 22:932–940, 2009. © 2009 Wiley‐Liss, Inc.     

电针对膝关节骨性关节炎患者疼痛改善及关节功能影响的荟萃分析

文题释义：电针法(electro-acupuncture)：将毫针刺入腧穴得气后,再通以接近人体生物电的脉冲电流,利用针和电的两种刺激,激发调整经络之气,以防治疾病的方法。 膝关节骨性关节炎(knee osteoarthritis,KOA)：又称为膝关节增生性关节炎、退行性膝关节炎,是中老年人常见的一种慢性骨关节病,主要病理特点为关节软骨退变、破坏、软骨下骨硬化、关节边缘软骨下骨增生,进而引起滑膜炎症、半月板损伤、游离体形成及关节外组织炎症等一系列病变,临床症状以膝关节的疼痛、肿胀、变形及活动受限为主。 背景：大量临床研究资料显示,电针治疗膝关节骨性关节炎具备起效速度快、治疗效果好、不良反应少等优点,但当前电针治疗该病缺乏多中心大样本的临床研究试验。 目的：应用荟萃分析法系统评价电针疗法对膝关节骨性关节炎患者疼痛改善及关节功能影响。 方法：检索中国知网(CNKI)、万方数据库(WF)、维普数据库(VIP)、美国医学在线(PubMed)、荷兰医学文献数据库(Embase)及国际循证医学图书馆(Cochrane Library)六大数据库中有关电针治疗膝关节骨性关节炎的临床随机对照试验文献,检索时限为各数据库自建库以来至2019年6月,经筛选后提取纳入研究的文献数据,采用Review Manager 5.3统计软件进行荟萃分析。 结果与结论：最终11篇文献被纳入研究,共727例膝关节骨性关节炎患者,其中采用单一电针疗法的治疗组366例,采用常规针刺或药物的对照组361例。与对照组比较,治疗组在提高总体有效率[OR=3.22,95%CI(2.13,4.87),Z=5.53,P < 0.000 01]及治愈率[OR=2.73,95%CI(1.80,4.15),Z=4.72,P < 0.000 01],降低目测类比VAS评分[MD=-1.00,95%CI(-1.71,-0.30),Z=2.80,P=0.005]、WOMAC评分[MD=-7.69,95%CI(-10.31,-5.07),Z=5.75,P < 0.000 01]及ISOA评分[MD=-2.22,95%CI(-3.74,-0.70),Z=2.86,P=0.004]等5个方面均有显著优势。基于以上Meta分析证据表明,电针治疗膝关节骨性关节炎的近期疗效确切,能够对患者疼痛症状及关节功能发挥积极效应且不良反应少。由于纳入研究的样本量较小、文献质量普遍不高及可能存在偏倚等因素,仍需更多更高质量的RCT研究来验证该研究的结论。 ORCID: 0000-0002-2201-5495(朱英) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

下腰椎上关节突及椎弓峡部相关解剖结构测量

目的 采用影像学的方法测量下腰椎中的上关节突以及椎弓峡部的相关解剖结构,并分析新型腰椎后路植骨术操作过程中的安全范围以及其与患者的身高、体重之间的关系。 方法 收集腰椎正侧位X线片正常的成年人300例,男女各150例,采用Digimizer软件测量第3~5腰椎（L3~5）椎体的上关节突的宽度、长度、深度、峡部深度、植骨长度以及绝对深度,并采用线性回归方程法分析这些指标与患者的升高、体重之间是否具有相关性。结果 男、女上关节突的宽度、长度、深度以及峡部的深度和绝对深度与患者的体重和身高之间无明显的相关性,P>0.05;植骨床的长度与身高之间具有显著的相关性,P<0.05,而与体重之间无相关性,P>0.05。 结论 采用影像学法测量下腰椎中的上关节突以及峡部的相关解剖结构,能够为腰椎后路植骨手术操作提供准确、可靠的数据支持。     

穴位注射改善膝骨关节炎患者疼痛及关节功能的Meta分析

文题释义： 穴位注射法：将药液注入穴位使药物直接应用于穴位,既发挥药物作用又能发挥经络传导的作用,通过药物刺激调节人体经络系统,达到舒筋通络的作用。 膝骨关节炎：又称为膝关节增生性关节炎、退行性膝关节炎,是中老年人常见的一种慢性骨关节病,主要病理特点为关节软骨退变、破坏、软骨下骨硬化、关节边缘软骨下骨增生,进而引起滑膜炎症、半月板损伤、游离体形成及关节外组织炎症等一系列病变,临床症状以膝关节的疼痛、肿胀、变形及活动受限为主。背景：大量临床研究显示,穴位注射治疗膝骨关节炎具有治疗效果好、不良反应少等优点,但当前穴位注射治疗该病缺乏多中心大样本的临床研究试验。 目的：应用Meta分析法系统评价穴位注射疗法对膝骨关节炎患者疼痛改善及关节功能的影响。 方法：检索中国知网、万方数据库、维普数据库、中国生物医学文献数据库、PubMed、Embase及Cochrane Library等数据库中自建库以来至2019年5月有关穴位注射治疗膝骨关节炎的临床随机对照试验,观察组为穴位注射或穴位注射联合其他疗法,对照组为不同于穴位注射疗法的其他治疗方法,检索语言中、英文不限,筛选后使用Review Manager 5.3软件提取文献数据进行Meta分析。 结果与结论：①共纳入16篇随机对照试验,涉及患者1 287例,其中观察组648例,对照组639例;②Meta分析显示,观察组的总体有效率、治愈率、Lysholm评分、日本膝关节功能评分均高于对照组[OR=3.23,95%CI(2.19,4.76),Z=5.91,P < 0.000 01;OR=1.86,95%CI(1.35,2.58),Z=3.74,P=0.000 2;MD=7.87,95%CI(2.66,13.08),Z=2.96,P=0.003;MD=9.16,95%CI(4.18,14.13),Z=3.61,P=0.000 3],两组目测类比评分、WOMAC评分、Lequesne指数及不良反应发生率比较差异均无显著性意义[MD=-1.11,95%CI(-2.29,0.07),Z=1.84,P=0.07;MD=-7.56,95%CI(-17.26,2.14),Z=1.53,P=0.13;MD=-0.46,95%CI(-1.62,0.71),Z=0.77,P=0.44;OR=1.31,95%CI(0.31,5.57),Z=0.37,P=0.71];③结果表明穴位注射治疗膝骨关节炎的疗效确切,但由于纳入研究的文献质量普遍不高及可能存在偏倚等因素,仍需更多更高质量的随机对照试验来验证结论。ORCID: 0000-0002-7859-7850(邓凯烽) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

An electromyographic exploratory study comparing the difference in the onset of hamstring and quadriceps contraction in patients with anterior knee pain

Idiopathic anterior knee pain in teenagers and young adults is a common condition. Patellar maltracking has been considered as a causative factor. The aim of our study was to investigate whether there was a difference in the timing of electromyographic (EMG) activity in the medial and lateral hamstring and quadriceps muscles of patients with anterior knee pain compared to asymptomatic control participants. This was a cross sectional observational study measuring EMG activation patterns. Two groups of participants were tested, one patient (mean age 15 years, n = 20) and one asymptomatic control (mean age 16 years, n = 17).Surface EMG (sampling rate 1000 Hz) was recorded from vastus medialis obliqus, vastus lateralis, and the medial and lateral hamstrings during three repetitions of maximal voluntary isometric contractions. The relative timing of the medial and lateral quadriceps and hamstrings was evaluated.The mean (95% confidence interval) difference between the groups in the lateral–medial hamstring onset timing was 53.8 (1.9 to 105.6) ms during the maximal contraction. An independent t test showed that this difference was statistically significant (p = 0.043). The differences between the groups in the relative VMO to VL onset did not reach statistical significance.The results of this study suggest that the lateral hamstrings contract significantly earlier in patients with AKP compared to healthy controls for this small cohort. This altered activation pattern could produce external rotation of the tibia on the femur and cause lateral patella tracking.     

坐位伸膝伴髋内收动作对髌股疼痛综合征患者股四头肌表面肌电信号的影响

目的 利用表面肌电图(surface electromyography, sEMG) 评估坐位伸膝伴或不伴髋内收动作下髌股疼痛综合征（patellofemoral pain syndrome,PFPS）患者股四头肌失衡程度。方法 PFPS病例组及正常对照组各30人,分别在坐位伸膝伴或不伴髋内收动作时检测股外侧肌(vastus lateralis,VL)及股内斜肌（vastus medialis oblique, VMO）表面肌电图,分析时域指标均方根振幅(root mean square,RMS)、积分肌电值（integrated EMG,IEMG）,比较其平衡关系。结果 坐位伸膝伴或不伴髋内收动作时病例组VL时域指标无显著性差异;VMO时域指标有统计学差异,伴髋内收时RMS、IEMG指标值较高,说明伴髋内收时VMO的肌肉募集增强。结论 坐位伸膝动作伴髋内收的动作可以对髌股疼痛综合征患者VMO肌电活动产生促进作用,从而使VL、VMO之间达到更好的平衡状态。     

The relationship between pain and dynamic knee joint loading in knee osteoarthritis varies with radiographic disease severity. A cross sectional study

ObjectiveIn a cross sectional study, we investigated the relationships between knee pain and mechanical loading across the knee, as indicated by the external knee adduction moment (KAM) during walking in patients with symptomatic knee OA who were distinguished by different radiographic disease severities.MethodsData from 137 symptomatic medial knee OA patients were used. Based on Kellgren/Lawrence (K/L) grading, the patients were divided into radiographically less severe (K/L ≤ 2, n = 68) or severe (K/L > 2, n = 69) medial knee OA. Overall knee pain was rated on a 10 cm visual analog scale, and peak KAM and KAM impulses were obtained from gait analyses. Mixed linear regression analyses were performed with KAM variables as the outcome, and pain and disease severity as independent variables, adjusting for age, gender, and walking speed.ResultsIn adjusted analyses, less severe patients demonstrated negative relationships between pain intensities and dynamic loading. The severe patient group showed no relationship between pain intensity and peak KAM, and a positive relationship between pain intensity and KAM impulse.ConclusionIn radiographically less severe knee OA, the negative relationships between pain intensity and dynamic knee joint loading indicate a natural reaction to pain, which will limit the stress on the joint. In contrast, either absent or positive relationships between pain and dynamic loading in severe OA may lead to overuse and accelerated disease progression. These findings may have a large potential interest for strategies of treatment in knee OA.     

Vitamin E ameliorates alterations to the articular cartilage of knee joints induced by monoiodoacetate and diabetes mellitus in rats

We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chondrocyte glycolysis inhibitor, monoiodoacetate (MIA) and the agent that induces diabetes mellitus, streptozotocin (STZ). Here we investigated the potential protective effect of the antioxidant and anti-inflammatory agent, vitamin E against MIA+STZ-induced OA. Therefore, rats were either injected once with MIA (2 mg/50 μL) + 65 mg/kg STZ before being sacrificed after 8 weeks (model group) or were treated immediately after MIA+STZ injections with vitamin E (600 mg/kg; thrice a week) before being sacrificed after 8 weeks (treatment group). Using scanning and transmission electron microscopy examinations, we observed in the model group a substantial damage to the articular cartilage of the knee joint as demonstrated by the destruction of the chondrocytes, territorial matrix, disrupted lacunae, collagen fibers, and profound chondrocyte ultrastructural alterations such as degenerated chondrocyte, irregular cytoplasmic membrane, damaged mitochondria and rough endoplasmic reticulum, vacuolated cytoplasm, presence of lipid droplets and different sizes of lysosomes, which were substantially but not completely protected by vitamin E. H&E stained sections of knee joint articular cartilage showed that MIA+STZ induced damage to the chondrocyte and territorial matrix. Vitamin E also significantly (p < .05) inhibited MIA+STZ-induced blood levels of the inflammatory biomarkers, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) that are known to be modulated in OA and diabetes. We conclude that vitamin E protects against MIA+STZ-induced knee joints injuries in rats, which is associated with the inhibition of biomarkers of inflammation.     

Anatomical study of the lateral collateral ligament and its circumference structures in the human knee joint

Thirty-six cadavers (55 sides) were used to observe the innervation of the lateral collateral ligament (LCL) and its circumference structures with gross anatomical and histological methods to clarify the cause of indistinct pain in the lateral part of the knee joint. The innervating branches of the LCL could be divided into three types: (1) from the muscular branch of the biceps femoris muscle at lower 1/3 level of the thigh; (2) from the common fibular nerve (CFN) at the higher level of the fossa poplitea; (3) from the CFN at the level of the caput fibular. Furthermore, the three branches could singly or plurally distribute to the LCL (six types). Two of the connecting tissue membranes surrounding the surface of LCL formed an incomplete sheath structure, and a shutting “gap” was observed between the two membranes. Fine peripheral nervous branches were also observed in the two of the membranes. On the other hand, three types of nerve endings in the LCL (Type Ι/Ruffini mechanoreceptor; Type ΙΙΙ/Golgi mechanoreceptor; Type ΙV/free nerve ending) were observed, and their presence was consistent with the ankle joint of humans. Therefore, the innervation of the two membranes (to form the shutting gap) in the surface of LCL may be associated with an indistinct pain when the knee joint is damaged.     

Types of afferents from the knee joint evoking sympathetic reflexes in cat inferior cardiac nerves

In anesthetized cats electrical stimulation of the medial articular nerve of the knee joint evoked sympathetic reflex discharges in inferior cardiac nerves. Low intensity single stimuli elicited early reflex discharges (A-reflexes, latency 70-90 ms, duration 110-200 ms) whereas short tetanic stimulation at higher intensities evoked, in addition, late reflexes (C-reflexes, latency 390-480 ms, duration 230-400 ms). An analysis of the relation between the conduction velocity and the electrical threshold of 231 single medial articular nerve fibers revealed that the A-reflex is mainly due to activation of Group II units, whereas the C-reflex is evoked by activity in unmyelinated Group IV fibers.     

骨癌痛外周机制研究进展

癌痛是临床晚期恶性肿瘤患者最常见的症状之一，也是破坏患者生活质量的重要因素。近年来出现的各种骨癌痛模型，为深入研究骨癌痛机制、寻找新的治疗方法提供了契机。骨癌痛具有复杂的发病机制。随着肿瘤的生长和骨质的破坏，病灶中与肿瘤相关的诸多因子不断释放（如前列腺素、内皮素、神经生长因子等），在肿瘤局部构成复杂而独特的微环境，持续激活并敏化支配骨组织的伤害性感受器。在骨癌痛发展的过程中，交互存在着炎症反应、神经损伤及其他组织损伤等病理变化，导致伤害性刺激传入信息增加，引起剧烈的疼痛     

Neuronal activation at the spinal cord and medullary pain control centers after joint stimulation: a c-fos study in acute and chronic articular inflammation

Chronic inflammatory pain induces short- and long-term central changes, which have been mainly studied at the spinal cord level. Supraspinal pain control centers intrinsically connected with the dorsal horn are also prone to be affected by chronic inflammatory pain. C-fos expression was used as a neuronal activation marker at spinal and supraspinal levels to i) compare acute and chronic articular inflammation, and ii) analyze the effects of brief innocuous or noxious stimulation of a chronically inflamed joint. Acute articular inflammation was induced by an inflammatory soup with prostaglandin E(2) and bradykinin, both at 10(-5) M. Chronic articular inflammation consisted of 14 days of monoarthritis. Early c-fos expression was studied 4 min after inflammatory soup injection or stimulation of the arthritic joint whereas late c-fos expression was evaluated 2 h after those stimuli. At the spinal cord, the analysis was focused on the dorsal horn (laminae I-V) and supraspinally, five major regions of the endogenous pain control system were considered: the caudal ventrolateral medulla (VLM), the dorsal reticular nucleus (DRt), the ventral reticular nucleus (VRt), the nucleus of the solitary tract (Sol) and the rostroventromedial medulla (RVM). Acute articular inflammation induced early and late increases in c-fos expression at the spinal level and late increases supraspinally whereas the effects of monoarthritis were more moderate and restricted to the spinal cord. When monoarthritic animals were subjected to gentle touch or bending of the joint, early increases in c-fos expression were detected supraspinally, but not at the spinal level. In this region, noxious mechanical stimulation induced late increases in non-inflamed animals and both early and late increases in monoarthritic rats. Supraspinally, noxious stimulation induced only late increases in c-fos expression. The present results show complex differences in the patterns of c-fos expression between the spinal cord and medullary areas of the pain control system during articular inflammation, which indicate that the somatosensory system is differentially affected by the installation of chronic pain.     

Anatomical study of the lateral femoral cutaneous nerve with special reference to minimally invasive anterior approach for total hip replacement

Background  Lesion of the lateral femoral cutaneous nerve (LFCN) represents the main complication during minimally invasive anterior approach dissection to the hip joint. The aim of this anatomical study was to describe the different presentation features of the LFCN at the thigh and particularly to determine the potential location of damage during minimally invasive anterior approach for total hip replacement. Methods  The LFCN was dissected bilaterally at the thigh under the inguinal ligament in 17 formalin-preserved cadavers. Branching patterns of the nerve were recorded and distances from the LFCN to the anterior superior iliac spine (ASIS) and the anterior margin of the tensor fascia lata (TFL) were measured to clarify skin incision positioning during minimally invasive anterior approach for total hip replacement. Results  The LFCN divided proximal to the inguinal ligament in 13 cases and distal to it in 21 cases. In the distal group the mean distance from the ASIS to the nerve division was 34.5 mm (10–72 mm). The gluteal branch crossed the anterior margin of the TFL 44.5 mm (24–92 mm) distally to the ASIS. In 18 cases the femoral branch did not cross the TFL and was located in the intermuscular space between TFL and sartorius. In the remaining 16 cases, this branch crossed the anterior margin of the TFL 46 mm (27–92 mm) distally to the ASIS. During minimally invasive anterior approach along the anterior border of the TFL, the LFCN was found to be potentially at risk between 27 and 92 mm below the ASIS. We used those informations to describe a map of “danger zones” for the LFCN or its two main branches. Conclusion  According to this study, numerous anatomical variations of the LFCN at the thigh should be considered when performing anterior approach to the hip joint. Different mechanisms of injury during surgery should be considered especially during minimally invasive total hip replacement, such as section of the gluteal or the femoral branch where it crosses the anterior margin of the TFL or stretching of the femoral branch due to retractors positioned into the intermuscular space between sartorius and TFL. According to the map of “danger zones” reported, the author policy consists of positioning the skin incision as lateral and distal to the ASIS as possible.     

Mechanism of pain and cytoskeletal properties in angioleiomyomas: An immunohistochemical study

Angioleiomyoma is a solitary subcutaneous tumor characterized by pain in about half of patients with this tumor, and the pathogenesis of this pain has been a cause of much debate. To clarify the mechanism of pain and cytoskeletal property of tumor cells, 50 angioleiomyomas were studied clinicopathologically and immunohistochemically. The tumors occurred preferentially on the extremities, particularly the lower leg (46%), and the female to male ratio was 1.9:1. They were classified into three histological subtypes: (i) solid (30 cases); (ii) venous (15 cases); and (iii) cavernous (five cases). The pain and/or tenderness were present in 26 out of 49 patients (52%), in which small nerve fibers immunoreactive for S-100 protein and PGP9.5 were identified within the capsule of 20 tumors (77%) and the tumor stroma of 18 (69%), irrespective of the histological subtypes. In 24 patients where the pain was absent or unknown, nerves were observed within the capsule of 19 tumors (79%) and tumor parenchyma of 10 (42%). Many cells in all 50 tumors were positive for a-smooth muscle actin, and a relatively large number of cells in many tumors were positive for vimentin, desmin and collagen type IV. Also, cytokeratin (CAM5.2) reactivity was scattered in a few cells of four tumors. From these findings, the peculiar pain of angioleiomyomas could be mediated by the nerve fibers especially located within the tumor parenchyma. Although the expression of intermediate filaments in angioleiomyomas was heterogeneous, the overall cytoskeletal features were of smooth muscle cell differentiation.