A light microscopical study on the structure of traumatic neuromas of the human lingual nerve

OBJECTIVE: To determine the morphologic characteristics of traumatic neuromas resulting from damage to the lingual nerve during the surgical removal of lower third molar teeth. STUDY DESIGN: Using light microscopy, we examined hematoxylin and eosin-stained sections of neuromas removed at the time of microsurgical nerve repair in 31 patients. Changes in fascicular pattern were quantified and evidence of inflammation was recorded. Statistical comparisons were made between the sections from patients with and without symptoms of dysesthesia, and with sections of normal lingual nerve obtained from organ donor retrieval patients. RESULTS: The neuromas were found to contain large numbers of small and haphazardly arranged regenerating nerve fascicles within a densely collagenous and fibroblastic stroma. The mean number of fascicles was 31 (+/- SD 28) in normal lingual nerve, but 462 (+/- 366) within traumatic neuromas. Mean fascicle diameter was 44 (+/- 10) microm in neuromas, but 273 (+/- 101) microm in normal nerve. A chronic mononuclear cell inflammatory infiltrate was observed in 42% of neuroma specimens, and histologic signs of inflammation were frequently seen in patients with symptoms of dysesthesia. CONCLUSIONS: Damage to the lingual nerve during third molar removal results in marked changes to the fascicular pattern and sometimes the presence of chronic inflammation in the injured nerve. These changes could contribute to the altered electrophysiological properties of axons trapped within traumatic neuromas, but we found no significant differences between the specimens studied from patients with or without symptoms of dysesthesia.     

Axon populations in cat lingual and chorda tympani nerves.

The lingual and chorda tympani nerves from five cats were examined so that normal axonal populations could be determined. After perfusion fixation, the chorda tympani and lingual nerves were removed and processed, and sections were taken from individual and combined nerves for both light and electron microscopy. The chorda tympani remained as a distinct group of smaller axons for at least 4 mm distal to its junction with the lingual nerve. The mean number +/- S.D. of myelinated axons in the chorda tympani central to the junction was 1322 (+/- 268) and in the lingual nerve central to the junction, 3227 (+/- 510). The counts were not significantly different distal to the junction, and there were no side-to-side differences. Mean myelinated axon circumferences were significantly smaller in the chorda tympani (12.86 +/- 0.87) than in the lingual nerve (22.79 +/- 1.99; p less than 0.01). The mean size of axons in the chorda tympani was slightly but consistently larger on the left (13.1 +/- 0.73) than on the right side (12.61 +/- 1.01; p less than 0.05). Distal to the junction, the average proportion of non-myelinated axons was 44% in both chorda tympani and lingual nerves.     

神经生长因子对下齿槽神经再生影响的实验研究

目的 探讨外源性神经生长因子（ｎｅｒｖｅ ｇｒｏｗｔｈ ｆａｃｔｏｒ,ＮＧＦ）对成年大白兔下齿槽神经再生的影响。方法 选用２４只成年日本大耳白兔,在双侧下齿槽神经各造成８ｍｍ缺损,神经近远端用硅胶管桥接,右侧硅小室 内注入外源性ＮＧＦ 作实验侧,左侧注入生理盐水为对照侧。对实验侧和对照侧的再生有髓神经纤维数目、传导速度、纤维横断面积和髓鞘厚度作相应比较。结果 ①ＮＧＦ能使有髓神经纤维数目明显增加;     

Reinnervation of teeth after segmental osteotomy

The reinnervation of 8 canine teeth denervated by segmental osteotomy has been investigated in cats by using electron microscopy. 12 weeks after osteotomy, the mean total number of axons at the canine apices was 36% of that found in normal animals. The myelinated axons were smaller than normal with thinner myelin sheaths. In non-myelinated fibres, there were fewer axons per fibre (Remak bundle) and more fibres containing only one axon. The proportions of myelinated and non-myelinated fibres were normal.     

大鼠正畸压力侧牙周膜神经纤维超微结构变化的研究

目的：观察正畸力作用下压力侧牙周膜神经纤维超微结构的改变。方法：利用透射电镜观察15只大鼠正畸牙齿移支2d、1周、2周和3周后，压力侧牙周膜神经纤维超微结构的改变。结果：牙齿移动2d后可见粗有髓神经纤维变性，3周后尚未完全恢复。细无髓神经纤维在2d时数量稍增多，1周时达到高,逐渐减少，至3周时数恢复 正常，部分神经纤维轻度变性；细有髓神经纤维数量无明显变化，其中部分神经纤维轻度变化性。结论：在正畸力作用下，牙周膜神经纤维均发生不同程度的变化，Aβ纤维严重变性，而Aδ纤维及C纤维轻度变性，C纤维主要表现为增生。     

An experimental study on regeneration of the inferior alveolar nerve after lyophilized nerve homografting in the rabbit

This study was designed to evaluate the differences between the regenerative process in cases of autogenous nerve grafting and lyophilized homologous nerve grafting. Rabbit inferior alveolar nerves (10 mm lengths) were resected and replaced with lyophilized homologous segments from the sciatic nerve. On the opposite side, the resected nerves were autogenously grafted. The experimental subjects were divided into autogenous nerve-graft and the lyophilized nerve-graft groups. Results. 1. Regenerating axons appeared in the autogenous-graft group 2 weeks after the operation and 4 weeks after the operation in the homografted lyophilized group. The difference in regeneration between the 2 groups was significant. 2. Regenerating axons in the autogenously grafted nerves made contact with remaining Schwann cells and endneural tubes. Axons in the homografted lyophilized nerves invaded along newly infiltrated Schwann cells and empty tube skeletal structures. The number of regenerating axons from outside the skeletal structure was greater than the number of regenerating axons from inside the skeletal structure. 3. In the case of autogenous grafting, nerve fibers of diameters greater than 3 microns increased 66.7% after 24 weeks; the corresponding figure for homografted lyophilized nerves was 48.4%. 4. In instances of autogenous grafting, 16 weeks after surgery, the ratio of distal proximal myelinated nerve fibers had grown. In cases of homografted lyophilized nerves, this tendency to increase continued until the twenty-fourth postsurgical week. 5. In both groups, it remained possible to record nerve action potentials 12 weeks after surgery. The sensory nerve conduction velocity of autogenously grafted nerves increased gradually to approach control values 24 weeks after surgery. That of homografted lyophilized nerves recovered more slowly. 6. Increases in number of nerve fibers with a diameter of more than 3 microns were proportional to the rate at which sensory nerve conduction velocity recovered.     

干细胞局部应用对缺损面神经再生效果的系统评价

目的 系统评价干细胞对面神经缺损的修复效果。方法 在Pubmed、Cochrane Library、Web of Science、Embase、Scopus及中国生物医学文献数据库检索关于评价干细胞对动物面神经再生效果的所有原始研究,2名专业人员独立完成文献筛选、数据提取及偏倚风险评估。使用RevMan 5.3软件及随机效应模型进行统计分析,分析结果以均数差（MD）及95%可信区间（CI）的形式呈现。对面神经的功能性评估（胡须运动评分、面瘫评分）及组织学评估（有髓纤维密度、纤维直径、髓鞘厚度、G比值）结果进行Meta分析。结果 从6个数据库共检索出4 614篇文献,15篇被纳入了Meta分析。干细胞组的胡须运动评分、面瘫评分、有髓纤维密度、髓鞘厚度均高于非干细胞组（P<0.05）,G比值小于非干细胞组（P=0.001）,纤维直径二者无统计学差异（P=0.08）。结论 干细胞具有促进面神经再生的潜能。     

Quantitation of nerve fibres in the primary and permanent canine and incisor teeth in man.

Myelinated and unmyelinated nerve fibres were counted and myelinated axons were measured in juxta-apical cross-sections of human primary and permanent canines and incisors. Fully-developed human primary canines had significantly more myelinated axons than permanent canines, but the number of unmyelinated axons was similar. Permanent incisors had significantly more myelinated nerve fibres entering the apex than did primary incisors, but the number of unmyelinated nerve fibres was similar. Primary canines and incisors lost nerve fibres early during resorption; evidence of degenerating myelinated axons was scant. A significant linear correlation existed between numbers of myelinated and unmyelinated axons for primary incisors and canines. The myelinated axon circumference was similar for primary and permanent teeth. Permanent teeth tended to have smaller groups of unmyelinated axons.     

去细胞同种异体移植面神经材料的制备

目的构建异体组织工程化面神经,提供具有仿生结构的支架。方法取8段长5 cm、直径2 mm兔的面神经,其中2段不行处理作为正常对照,其余6段分成3组,用3%三硝基甲苯和4%脱氧胆酸钠分别萃取1、2和3次,在萃取神经和未萃取神经的中段取材,行苏木精-伊红染色、Masson染色和S-100免疫组化染色,在光镜和电镜下观察神经萃取前后形态学的变化。结果用三硝基甲苯和脱氧胆酸钠萃取后,面神经内的细胞消失,而纤维性支架结构与未经萃取的神经相仿,电镜下可见萃取后的神经由空的神经基膜管和管之间的胶原纤维构成。随着萃取次数的增加,神经内残留的S-100蛋白减少,但反复萃取后神经的支架结构受破坏。结论用三硝基甲苯和脱氧胆酸钠萃取2次可去除兔面神经的细胞而保留完整的神经基膜管和纤维支架结构,是制备具有仿生结构的组织工程化面神经支架较为理想的方法。     

下牙槽神经挤压伤后再生的实验研究

目的 探讨外源性神经生长因子（NGF）对成年大白兔下牙槽神经挤压伤后再生的影响。方法 30只成年新西兰大白兔，下牙槽神经挤压伤后，随机分成2组，即对照组和用药组，对二组的再生有髓神经纤维传导速度、数目、直径和髓鞘厚度作比较。结果 NGF能使理生有髓神经纤维数目、直径、髓鞘厚度增加；术后相同时间NGF组神经传导速度大于对照组。。结论 外源性神经生长因子能够促进下牙槽神经损伤后再生及功能的恢复。     

去细胞同种异体移植面神经材料的制备

目的：探讨如何构建异体组织工程化面神经,提供具有仿生结构的支架：方法：取8段长5cm、直径2mm兔的面神经,其中6段用3％三硝基甲苯和4％脱氧胆酸钠分别萃取1、2和3次,在萃取神经和未萃取神经的中段取材,行HE染色、Masson染色和S-100免疫组化染色,在光镜和电镜下观察神经萃取前后形态学的变化：结果：用三硝基甲苯和脱氧胆酸钠萃取后,面神经内的细胞消失,而纤维性支架结构与未经萃取的神经相仿,电镜下可见萃取后的神经由空的神经基底膜管和管之间的胶原纤维构成。随着萃取次数的增加,神经内残留的S-100蛋白显著减少,但反复萃取后神经的支架结构受破坏：结论：用三硝基甲苯和脱氧胆酸钠萃取2次可去除兔面神经的细胞而保留完整的神经基底膜管和纤维支架结构,是制备具有仿生结构的组织工程化面神经支架较为理想的方法。     

Morphometric analysis of sural nerve in elderly diabetes mellitus

Biopsy specimens of the sural nerve obtained from 28 middle-aged and elderly diabetics suffering from neuropathy were studied morphometrically. Myelinated nerve fiber density, especially large fibers, was decreased, and the bimodal distribution of myelinated fiber diameter shifted to unimodal distribution containing only a small fiber peak and the mean diameter of myelinated fiber was decreased. An insulin-treated group and a group with severe retinopathy showed a prominent decrease of myelinated fiber density; the severity and duration of diabetes may be a factor in this decrease. Large unmyelinated nerve fibers were also decreased and the mean diameter of unmyelinated fibers was reduced. Three patients with prominent autonomic nervous system symptoms showed a significant reduction of total unmyelinated fibers. The linear correlation between the square root of the transverse axis cylinder area and the number of myelin lamellae was obscured, and the plots were towards two directions, axonal atrophy and remyelination in diabetes. The latter process tended to be dominant in the middle-aged patients, but the importance of these two processes was reversed with age. To discuss the morphological changes of the sural nerve in diabetic neuropathy, the influence of aging as well as the duration, severity and clinical symptoms should be considered.     

内翻静脉移植修复下牙槽神经缺损的动物实验研究

目的：探索静脉移植修复周围神经缺损的一种新方法,进一步提高周围神经修复的效果。方法：将切取的静脉段的管壁内外翻转面为内翻静脉,然后移植修复８ｍｍ的兔下牙槽神经缺损。术后２０周,采用神经电生理、组织形态学检查与常规静脉移植方法相比较。结果：术后２０周,内翻静脉移植在神经兴奋传导速度、再生神经纤维数目及髓鞘厚度上均有明显提高（Ｐ〈０．０５）。结论：内翻静脉移植能促进神经再生,是一种疗效较好、方法简便的     

Peripheral nerve regeneration using a three dimensionally cultured schwann cell conduit

The use of artificial nerve conduit containing viable Schwann cells is one of the most promising strategies to repair peripheral nerve injury. To fabricate an effective nerve conduit whose microstructure and internal environment are more favorable in nerve regeneration than those currently existing, a new three-dimensional (3D) Schwann cell culture technique using Matrigel and dorsal root ganglion (DRG) was developed.Nerve conduit of 3D arranged Schwann cells was fabricated using direct seeding of freshly harvested DRG into Matrigel-filled silicone tubes (inner diameter 1.98 mm, 14 mm length) and in vitro rafting culture for 2 weeks. The nerve regeneration efficacy of 3D cultured Schwann cell conduit (3D conduit group, n = 6) was assessed using an Sprague-Dawley rat sciatic nerve defect of 10 mm and compared with that of a silicone conduit filled with Matrigel and Schwann cells prepared with the conventional plain culture method (two-dimensional [2D] conduit group, n = 6). After 12 weeks, sciatic function was evaluated with sciatic function index (SFI) and gait analysis, and histomorphology of nerve conduit and the innervated tissues of sciatic nerve were examined using image analyzer and electromicroscopic methods.The SFI and ankle stance angle in the functional evaluation were -60.1 +/- 13.9, 37.9 degrees +/- 5.4 degrees in the 3D conduit group (n = 5) and -87.0 +/- 12.9, 32.2 degrees +/- 4.8 degrees in the 2D conduit group (n = 4). The myelinated axon was 44.91% +/- 0.13% in the 3D conduit group and 13.05% +/- 1.95% in the 2D conduit group. In the transmission electron microscope study, the 3D conduit group showed more abundant myelinated nerve fibers with well-organized and thickened extracellular collagen than the 2D conduit group, and the gastrocnemius muscle and biceps femoris tendon in the 3D conduit group were less atrophied and showed decreased fibrosis with less fatty infiltration than the 2D conduit group. A new 3D Schwann cell culture technique was established, and nerve conduit fabricated using this technique showed much improved nerve regeneration capacity than the silicone tube filled with Matrigel and Schwann cells prepared from the conventional plain culture method.     

Quantitative diameter analysis of lingual nerve axons in man

Previous studies on axon counts and fiber-diameter spectra in lingual nerves have been carried out only on animal models. This study reports an histological investigation on a series of 20 lingual nerves removed post mortem from human subjects. The results show wide variation in the myelinated fiber counts--a variation which does not appear to be related to the ages of the subjects. When the results are compared with those of a previous study (Heasman and Beynon, 1983), it is seen that the lingual nerve:inferior dental nerve ratio of axon counts is not a consistent index. The fiber-diameter spectrum for the human lingual nerve is characterized by a bimodal curve with the more pronounced peak in the small-diameter fiber range.     

Ultrastructural evidence of nerve and oxytalan fibre associations in the endoneurium of human periodontal ligament

Human periodontal ligament from premolars contained numerous fibres of the oxytalan meshwork system affiliated with unmyelinated endoneurium and myelinated nerves in the endoneurium. These fibres consisted of bundles of microfibrils and were present within 0.5 μ of Schwann cells and their unmyelinated axons. This ultrastructural association has not been previously demonstrated.     

Clinical considerations from axon-myelin relationship in human inferior alveolar nerve

A histological study analysed the axon-myelin relationships in human inferior alveolar nerve fibres in both transverse and longitudinal sections. Observations on fibres cut in transverse section showed variation in myelin thickness upon axons having approximately the same diameter. Large diameter axons had relatively thinner myelin sheaths than small-diameter axons. A longitudinal reconstruction of a 470 micron length of fibre demonstrated the presence of 13 Schmidt-Lantermann clefts. The surgical and clinical implications of these finding are discussed.     

Peripheral mechanisms for the initiation of pain following trigeminal nerve injury

Injury to a branch of the trigeminal nerve may lead to the development of chronic pain in the affected area. The etiology of this condition is not clear, but there is strong evidence to suggest that spontaneous and mechanically induced neural discharge from the injury site plays a crucial role. In laboratory studies, we have characterized this discharge following injury to the inferior alveolar or lingual nerves and have shown a temporal association with the accumulation of neuropeptides in the damaged axons. Substance P, calcitonin gene-related peptide, and vasoactive intestinal polypeptide were all found to be capable of increasing the discharge when applied systemically, and enkephalin caused a decrease. There were also changes in the expression of specific sodium channels and nitric oxide synthase, both at the injury site and in the trigeminal ganglion. Studies on lingual nerve neuromas taken from patients undergoing nerve repair also revealed accumulation of peptides, as well as inflammatory and structural changes, but the presence of these features did not correlate directly with the reported symptoms. The application of corticosteroids to an experimental injury site decreased the mechanically induced discharge, and the anticonvulsant carbamazepine reduced the spontaneous discharge in some axons. Some of the responses that result from damage to a branch of the trigeminal nerve appear to differ from those that follow damage to other peripheral nerves. These differences will need to be taken into account when developing new therapeutic approaches for the management of injury-induced trigeminal pain.     

Sciatic nerve regeneration induced by transplantation of in vitro bone marrow stromal cells into an inside-out artery graft in rat

Traumatic injury to peripheral nerves results in considerable motor and sensory disability. Several research groups have tried to improve the regeneration of traumatized nerves by invention of favorable microsurgery. Effect of undifferentiated bone marrow stromal cells (BMSCs) combined with artery graft on peripheral nerve regeneration was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using an artery graft (IOAG) filled with undifferentiated BMSCs (2 × 10⁷ cells/mL). In control group, the graft was filled with phosphated buffer saline alone. The regenerated fibers were studied 4, 8 and 12 weeks after surgery. Assessment of nerve regeneration was based on behavioral, functional (Walking Track Analysis), electrophysiological, histomorphometric and immuohistochemical (Schwann cell detection by S-100 expression) criteria. The behavioral, functional and electrophysiological studies confirmed significant recovery of regenerated axons in IOAG/BMSC group (P < 0.05). Quantitative morphometric analyses of regenerated fibers showed the number and diameter of myelinated fibers in IOAG/BMSC group were significantly higher than in the control group (P < 0.05). This demonstrates the potential of using undifferentiated BMSCs combined with artery graft in peripheral nerve regeneration without limitations of donor-site morbidity associated with isolation of Schwann cells. It is also cost saving due to reduction in interval from tissue collection until cell injection, simplicity of laboratory procedures compared to differentiated BMSCs and may have clinical implications for the surgical management of patients after facial nerve transection.     

Innervation of the temporomandibular joint

A bstract — The human temporomandibular joint in transverse and longitudinal section was found to have two types of mechanoreceptors. One of capsular form approximately 40 times 200 μm innervated by myelinated nerve fibres 8 μm in diameter and the other corresponding to the Golgi tendon organ was innervated by myelinated nerve fibres 15 μm in diameter which on entering the tendon organ lost their myelin sheaths.