RESUMEN
Neuromas of the hand and wrist are common causes of peripheral nerve pain. Neuromas are formed after the nerve sustains an injury, and they can be debilitating and painful. The diagnosis is made by a thorough history and physical examination. The treatment options are quite varied, but conservative measures tailored to the patient should be initiated first. No surgical treatment has been proven superior to others or to nonsurgical treatment.
Asunto(s)
Desnervación/métodos , Mano , Neuroma/cirugía , Muñeca , Animales , Humanos , Microscopía Electrónica , Neuralgia/etiología , Neuroma/diagnóstico , Neuroma/etiología , Neuroma/ultraestructura , Traumatismos de los Nervios Periféricos/complicaciones , Nervios Periféricos/ultraestructura , RatasRESUMEN
Keratinocytes play an important role in the dialog between skin and cutaneous sensory neurons. They are an essential source of cutaneous nerve growth factor (NGF), a neurotrophin that contributes to persistent pain in inflammation and neuropathy. We studied the interaction of human keratinocytes (hKTs) and regenerating afferent nerve fibers by transplanting hKTs into a ligated and transected peripheral nerve. The hKTs self-assembled into a multi-laminar spheroid cellular structure resembling the stratum spinosum of epidermis. Axonal sprouts surrounded the structure although they were excluded from entry. Levels of NGF were elevated at the transplant site. Whole cell patch-clamp recordings from primary afferent neurons whose cut axons were present near the transplanted hKTs displayed extreme hyperexcitability. These neurons generated high frequency trains of action potentials during step depolarization stimuli, and they sometimes showed afterdischarge and fired spontaneously at resting membrane potential. This spontaneous firing originated from subthreshold membrane potential oscillations. The animals with the hKT transplants exhibited spontaneous pain behavior manifest as autotomy. The results demonstrate that an interaction between injured/regenerating nerve fibers and keratinocytes such as may occur during wound healing, results in afferent hyperexcitability and pain. These results have implications for persistent pain associated with burn and traumatic skin injuries.
Asunto(s)
Queratinocitos/fisiología , Ciática/complicaciones , Ciática/cirugía , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Análisis de Varianza , Animales , Axones/metabolismo , Axones/patología , Axones/ultraestructura , Trasplante de Células/métodos , Células Cultivadas , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Ganglios Espinales/citología , Humanos , Queratinocitos/trasplante , Queratinocitos/ultraestructura , Ratones , Ratones Desnudos , Microscopía Electrónica de Transmisión/métodos , Fibras Nerviosas Amielínicas/fisiología , Factor de Crecimiento Nervioso/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neuroma/patología , Neuroma/ultraestructura , Dimensión del Dolor/métodos , Técnicas de Placa-Clamp/métodos , Cloruro de Potasio/farmacología , Ciática/patología , Ciática/fisiopatología , Células Receptoras Sensoriales/fisiología , Células Receptoras Sensoriales/ultraestructuraRESUMEN
AIMS: To determine the ultrastructural characteristics of axons in traumatic neuromas of the human lingual nerve during the surgical removal of lower third molar teeth and to establish whether any characteristics were different between patients with dysesthesia and patients without dysesthesia. METHODS: Transmission electron microscopy was used to determine the ultrastructural morphological characteristics of human lingual nerve neuromas (n = 34) removed at the time of microsurgical nerve repair. From a sample population of myelinated and nonmyelinated fibers within the neuromas, fiber diameter, myelin thickness, g-ratio, and the number of mitochondria per axon were quantified. Comparisons were made with normal control lingual nerve specimens (n = 8) removed at the time of organ donor retrieval. RESULTS: Significant differences in ultrastructural morphology were found between the neuromas and control nerves. The neuromas contained a higher proportion of small (2- to 8-microm diameter) myelinated nerve fibers than controls, and the mean myelinated fiber diameter was significantly lower in neuromas than in controls. Mean myelin sheath thickness was significantly thinner in neuromas (0.6 +/- 0.1 microm) than in controls. However, the g-ratio, which is a measure of the myelination status of the nerve fibers in relation to their diameter, was found to be similar in each group, suggesting a normal process of myelination in the damaged axons. Nonmyelinated axon diameter was also significantly smaller in the neuromas than in the controls, and Schwann cells were found to sheathe more nonmyelinated axons in neuromas than in controls. The ratio of nonmyelinated to myelinated axons was significantly higher in neuromas than in controls. However, no significant differences were found between patients with dysesthesia and those without dysesthesia. CONCLUSION: Damage to the lingual nerve results in marked changes to axon diameter, myelin sheath thickness, and Schwann cell-axon relationships. These ultrastructural changes could contribute to the altered electrophysiological properties of axons trapped within neuromas. However, no significant differences in the ultrastructural characteristics studied were found between specimens from patients with or without symptoms of dysesthesia.
Asunto(s)
Axones/ultraestructura , Traumatismos del Nervio Craneal/complicaciones , Neoplasias de los Nervios Craneales/ultraestructura , Traumatismos del Nervio Lingual , Neuroma/ultraestructura , Adolescente , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Neoplasias de los Nervios Craneales/etiología , Femenino , Humanos , Modelos Lineales , Nervio Lingual/cirugía , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Mitocondrias/ultraestructura , Vaina de Mielina/ultraestructura , Neuroma/etiología , Parestesia/etiología , Células de Schwann/ultraestructura , Estadísticas no ParamétricasRESUMEN
Peripheral nerve injury is sometimes followed by the development of persistent painful sensory disorders, such as dysaesthesia. The aetiology of these disorders is not clear, but abnormal behaviour of damaged axons at the injury site is likely to be involved. In this study, we quantified some ultrastructural characteristics that may be related to the development of abnormal spontaneous activity, sympathetic interactions, and fibre-to-fibre crosstalk. Using electron microscopy, we have determined the frequency and extent of axonal exposure and close apposition among non-myelinated axons from 34 traumatic neuromas of the human lingual nerve. These specimens were removed at the time of microsurgical nerve repair, and the presence or absence of symptoms of dysaesthesia was determined pre-operatively. Comparisons were also made with eight normal control lingual nerve specimens obtained from patients undergoing organ donor retrieval. More non-myelinated axons showed signs of axonal exposure in traumatic neuromas (26%) than in controls (5%), and exposure was higher in nerve-end neuromas (31%) than in neuromas-in-continuity (22%). In addition, the proportion of the non-myelinated axolemma that was exposed was significantly higher in neuromas (32%) than in controls (21%). The frequency of close apposition between neighbouring non-myelinated axons was also higher in neuromas (11%) than in controls (0.35%). The majority of axons showing signs of exposure or close apposition had diameters <1 microm. These ultrastructural changes may account for some of the altered electrophysiological properties of axons within neuromas. However, no significant correlations were found between these ultrastructural characteristics and the patients' reported symptoms of dysaesthesia.
Asunto(s)
Comunicación Celular/fisiología , Nervio Lingual/patología , Fibras Nerviosas Amielínicas/ultraestructura , Neuroma/ultraestructura , Adolescente , Adulto , Humanos , Nervio Lingual/ultraestructura , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Neuroma/patologíaRESUMEN
Los tumores del sistema periférico en oftalmología son poco frecuentes y algunos excepcionales. Los derivados de las simpaticogonias o neuroblastos constituyen el espectro de los neuroblastomas, ganglioneuroblastomas y ganglioneuromas; los derivados de los troncos nerviosos son los neurofibromas, schwannomas y neuromas. Los paragangliomas y quimiodectomas son excepcionales y el tumor de tritón es una verdadera rareza. Algunas de estas neoplasias se encuentran formando parte de síndromes complejos con clara connotación heredofamiliar. Se realiza una revisión clinicopatológica cuidadosa de estas entidades.
Asunto(s)
Ojo/patología , Neoplasias , Células APUD , Sistema Nervioso Periférico/patología , Paraganglioma , Ganglioneuroblastoma/ultraestructura , Neurilemoma/ultraestructura , Neuroblastoma/ultraestructura , Neurofibroma , Neuroma/ultraestructuraRESUMEN
Neuroma can be painful and physically and psychologically disabling. Among the many methods of treatment available, one of the more successful is centrocentral nerve union with an autologous graft. However, it cannot be used in small nerves that lack two fascicles. This study evaluated neuroma prevention in an end-to-side anastomosis, a new technique applicable to all nerves. The lateral branch of the right sciatic nerve in 20 rats was transected at the midthigh level. The proximal segment was looped back to the main nerve and an end-to-side epineural anastomosis was performed. The lateral branch of the left sciatic nerve was transected to serve as a control, and the proximal nerve stump was closed by interrupted epineural sutures. The animals were sacrificed 12 weeks after the operation. Histologic analysis of specimens from the 12 controls showed neuroma formation. Specimens from 12 side-to-end anastomoses contained regenerated nerve tissues and formed smaller masses compared with that of the controls. The regenerated tissues at the anastomoses were orientated more orderly than were tissues from the controls in 75% of cases. The differences were statistically significant. Electron microscopic study on specimens from the remaining eight controls showed the presence of abundant large abnormal myelinated fibers (10-15 microns) with thick irregular myelin sheaths scattered among smaller myelinated fibers (2-10 microns) that had thin myelin sheaths. In the remaining eight end-to-side anastomoses, large abnormal myelinated fibers were absent. The myelinated fibers were 2 to 10 microns in diameters and had a normal appearance with thin myelin sheaths. End-to-side anastomosis formed a smaller mass of regenerated nerve tissues. Ultrastructurally they were formed better and orientated more orderly resembling normal nerve.
Asunto(s)
Neuroma/prevención & control , Neoplasias del Sistema Nervioso Periférico/prevención & control , Nervio Ciático/cirugía , Neuropatía Ciática/prevención & control , Anastomosis Quirúrgica/métodos , Animales , Microscopía Electrónica , Neuroma/ultraestructura , Neoplasias del Sistema Nervioso Periférico/ultraestructura , Distribución Aleatoria , Ratas , Nervio Ciático/lesiones , Nervio Ciático/ultraestructura , Neuropatía Ciática/patología , Técnicas de Sutura , Factores de TiempoRESUMEN
The ultrastructural localization of sympathetic axons was investigated in normal rat sciatic nerves and experimental sciatic nerve neuromas. The best ultrastructural localization of noradrenaline in the dense-cored vesicles of sympathetic axons was accomplished following pretreatment of rats with nialamide and 5-hydroxy dopamine, followed by fixation according to the modified chromaffin technique of Tranzer and Richards (1976). After such preparation, sympathetic axons containing 5-hydroxy dopamine-labelled dense-cored vesicles could be identified in normal sciatic nerve. Large accumulations of labelled dense-cored vesicles were also found in acute neuromas, up to 1 week after nerve section. Much smaller numbers of dense-cored vesicles could be identified in chronic neuromas from 2 to 3 weeks following nerve section. Sympathetic axons could also be identified following electron probe X-ray microanalysis of the tissue sections, using chromium detection as the marker for the noradrenaline-containing dense-cored vesicles. Unusual configurations of Schwann cell subunits, which enclosed myelinated fibres and sympathetic axon sprouts within the same basal lamina, were identified in the acute neuromas, 3-7 days after nerve section. Such configurations may be of relevance to the pathophysiological interaction which develops between sympathetic efferent and sensory fibres in peripheral nerve neuromas.
Asunto(s)
Fibras Adrenérgicas/ultraestructura , Axones/ultraestructura , Neuroma/patología , Nervio Ciático/patología , Fibras Adrenérgicas/química , Fibras Adrenérgicas/efectos de los fármacos , Animales , Axones/química , Axones/efectos de los fármacos , Células Cromafines/química , Células Cromafines/ultraestructura , Microanálisis por Sonda Electrónica , Femenino , Hidroxidopaminas/análisis , Microscopía Electrónica , Inhibidores de la Monoaminooxidasa/farmacología , Degeneración Nerviosa/efectos de los fármacos , Degeneración Nerviosa/fisiología , Fibras Nerviosas Mielínicas/química , Fibras Nerviosas Mielínicas/ultraestructura , Neuroma/ultraestructura , Neuronas Eferentes/química , Neuronas Eferentes/efectos de los fármacos , Neuronas Eferentes/ultraestructura , Nialamida/farmacología , Norepinefrina/análisis , Ratas , Ratas Wistar , Nervio Ciático/química , Fijación del TejidoRESUMEN
Axons in intact peripheral nerve trunks constitute independent afferent and efferent communication channels. However, when nerves are severed, several different forms of axon-axon cross-excitation develop in association with the injury site. In this study we have examined experimental sciatic nerve-end neuromas in rats with special interest in the compartmentalization of individual axons, and the barriers that separate close neighbours. At postinjury times at which functional coupling is known to occur, neuromas were found to contain many examples of axons in which adjacent membrane faces come into close contact without an intervening Schwann cell process. These occur in bundles containing from two to as many as 30 individual nerve fibres wrapped in a common Schwann cell sheath. The surface area of close apposition between axon pairs ranges up to several tens of micron2. Closely apposed axon profiles may be outgrowing branches of a single parent axon, but anterograde tracer data indicate that many belong to independent neurons. Closely apposed axons are separated from one another, and from associated Schwann cell processes, by a cleft about 130 A wide. No synapses, gap junctions or tight junctions were observed. Extracellular tracer studies using La3+ and Ruthenium Red indicated that the cleft system is patent, permitting the free diffusion of small molecules between the space adjacent to the axolemma and the bulk extracellular compartment. Together, these data provide a structural basis for interfibre interactions based on local electrical current flow (ephaptic crosstalk), as well as coupling mediated by K+ ions and neurotransmitter molecules.
Asunto(s)
Axones/ultraestructura , Terminaciones Nerviosas/ultraestructura , Neuroma/ultraestructura , Animales , Masculino , Ratas , Ratas Wistar , Células de Schwann/ultraestructuraAsunto(s)
Factor I del Crecimiento Similar a la Insulina/farmacología , Mycoplasma/fisiología , Neuroma/patología , Adulto , Animales , División Celular , Línea Celular Transformada , Cromosomas/ultraestructura , ADN de Neoplasias/análisis , ADN de Neoplasias/genética , Fibroblastos/patología , Citometría de Flujo , Humanos , Cariotipificación , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Neuroma/genética , Neuroma/ultraestructura , Células de Schwann/patologíaRESUMEN
Electron microscopic evaluation was investigated in surgical specimens of interdigital neuroma. Edema of the endoneureum, fibrosis beneath the perineurium, axonal degeneration and necrosis suggest nerve damage occurs secondary to mechanical impingement in the etiology of interdigital neuroma.
Asunto(s)
Metatarso , Neuroma/ultraestructura , Adulto , Anciano , Femenino , Humanos , Microscopía Electrónica , Persona de Mediana EdadRESUMEN
Two weeks following chronic partial constriction of rat sciatic nerve, the perineurium was disrupted and a neuroma had formed at the constriction site in all nerves (n = 5). Axon counts demonstrated an 84-99% and a 62-84% decrease in myelinated and unmyelinated axons respectively, distal to the lesion. Distally, the majority of surviving myelinated axons had diameters of less than 5.0 microns. There was considerable disparity in fiber loss from animal to animal, but similar behavioral changes were demonstrated by all animals. These results are discussed with reference to previously published data and possible mechanisms underlying the behavioral manifestations of this neuropathy model.
Asunto(s)
Neuroma/fisiopatología , Neoplasias del Sistema Nervioso Periférico/fisiopatología , Nervio Ciático/lesiones , Animales , Axones/ultraestructura , Masculino , Microscopía Electrónica , Fibras Nerviosas Mielínicas/ultraestructura , Regeneración Nerviosa , Neuroma/patología , Neuroma/ultraestructura , Neoplasias del Sistema Nervioso Periférico/patología , Neoplasias del Sistema Nervioso Periférico/ultraestructura , Ratas , Ratas Endogámicas , Células de Schwann/citología , Células de Schwann/patología , Células de Schwann/ultraestructura , Nervio Ciático/patología , Nervio Ciático/ultraestructuraRESUMEN
Injured sensory axons with endings trapped in a nerve-end neuroma become a source of abnormal impulse discharge and neuropathic pain. We have examined the ultrastructure of such endings anterogradely transported WGA-HRP and freeze-fracture replication, with emphasis on the postinjury period during which the abnormal neural discharge is maximal. Most axons ended in a terminal swelling, depleted of myelin but surrounded by Schwann cell processes. These 'neuroma endbulbs' were richly packed with membrane-bound organelles, and had a smoothly undulating surface with (in neuromas of several weeks standing) a moderate number of short filopodia. Massive sprouting did not occur until several months postinjury. Both p- and e-faces of endbulb axolemma had larger intramembranous particles, on average, than corresponding internodal membrane of control axons. This change, interpreted as indicating remodelling of axolemmal channel (and perhaps receptor) content, may be related to the abnormal electrical behavior of neuroma afferents.
Asunto(s)
Axones/ultraestructura , Terminaciones Nerviosas/ultraestructura , Neuroma/ultraestructura , Neuronas Aferentes/ultraestructura , Neoplasias del Sistema Nervioso Periférico/ultraestructura , Nervio Ciático , Animales , Transporte Axonal , Citoplasma/ultraestructura , Técnica de Fractura por Congelación , Peroxidasa de Rábano Silvestre , Masculino , Microscopía Electrónica , Orgánulos/ultraestructura , Ratas , Ratas Endogámicas , Aglutininas del Germen de TrigoRESUMEN
The perineurial cells that make up the perineurium of peripheral nerve fascicles are characterized by distinct ultrastructural features, including non-branching thin cytoplasmic processes coated by an external lamina and joined at their ends by a tight junction, few organelles, actin and vimentin filaments, and numerous pinocytotic vesicles. Perineurial cells are immunoreactive for vimentin and epithelial membrane antigen (EMA) but not for the Schwann cell markers S-100 protein and Leu-7. The cytogenesis of the perineurium remains disputable, with morphologic, immunohistochemical, and experimental evidence supporting origin from the fibroblast, Schwann cell, and arachnoid cap cell. Ultrastructural studies more recently supported by immunolocalization of EMA have detected hyperplastic and neoplastic perineuriallike cells in a number of pseudoneoplastic lesions and true neoplasms, notably localized hypertrophic neuropathy, neurofibromas of various types, and perineurioma.
Asunto(s)
Tejido Conectivo/patología , Nervios Periféricos/patología , Neoplasias del Sistema Nervioso Periférico/patología , Tejido Conectivo/química , Tejido Conectivo/ultraestructura , Humanos , Inmunohistoquímica , Microscopía Electrónica , Neurofibroma/química , Neurofibroma/patología , Neurofibroma/ultraestructura , Neuroma/química , Neuroma/patología , Neuroma/ultraestructura , Nervios Periféricos/química , Nervios Periféricos/ultraestructura , Neoplasias del Sistema Nervioso Periférico/química , Neoplasias del Sistema Nervioso Periférico/ultraestructuraRESUMEN
A 6-year-old Japanese girl developed five asymptomatic nodules at the amputated edges of her right index, middle, and ring fingers. The amputation had been performed after she suffered deep burns at the age of 3 months. A histological diagnosis of traumatic neuroma was made.
Asunto(s)
Muñones de Amputación , Quemaduras/complicaciones , Traumatismos de los Dedos/complicaciones , Dedos , Neuroma/patología , Quemaduras/cirugía , Niño , Femenino , Traumatismos de los Dedos/patología , Traumatismos de los Dedos/cirugía , Humanos , Neuroma/etiología , Neuroma/ultraestructuraRESUMEN
The formation of neuromas after neonatal nerve injury was studied in rats. In neonatal pups, the sciatic nerve was cut and tightly ligated, and a portion of the distal stump was removed. After 6-10 weeks, a nerve-end neuroma had formed in about 70% of the animals. In the remaining animals the nerve had grown on the side of the ligature. The end structure of the neuroma axons was studied using anterogradely transported WGA-HRP injected into the L5 dorsal root ganglion. HRP labeling occurred in the entire proximal sciatic nerve. In the neuroma, labeled fibers branched profusely and either terminated with minor end swellings or turned in the retrograde direction. Immunohistochemistry showed that the fibers which projected into the neuroma presented a moderate immunoreactivity to substance P and neuropeptide Y and a strong reactivity to calcitonin gene-related peptide. The results show that many sensory and sympathetic sciatic nerve fibers survive chronic axotomy in the newborn and contribute to the formation of nerve-end neuromas. There are, however, important structural differences between adult and neonatally induced neuromas.
Asunto(s)
Axones/ultraestructura , Terminaciones Nerviosas/ultraestructura , Neuroma/ultraestructura , Neuropéptidos/metabolismo , Neoplasias del Sistema Nervioso Periférico/ultraestructura , Nervio Ciático , Animales , Axones/metabolismo , Desnervación , Peroxidasa de Rábano Silvestre , Inmunohistoquímica , Neuroma/metabolismo , Neoplasias del Sistema Nervioso Periférico/metabolismo , Ratas , Ratas Endogámicas , Aglutininas del Germen de TrigoRESUMEN
In mammals, cut sensory axons trapped in a nerve end neuroma have been shown to develop hyperexcitability, and to become a source of ectopic afferent discharge and abnormal sensation. We have explored cellular mechanisms underlying neuroma electrogenesis. First we confirmed that ectopic neuroma discharge develops in injured afferents in the electrosensory lateral line nerve of the weakly electric fish Apteronotus, as it does in mammals. Then, using previously characterized antibodies that specifically recognize Na+ channel proteins in this species, we obtained light and electron microscopic evidence of abnormally intense immunolabelling of axolemma at the injury site. Accumulation of excess Na+ channels in afferent endings in neuromas could account for their electrical hyperexcitability.
Asunto(s)
Membrana Celular/metabolismo , Neuroma/metabolismo , Neuronas Aferentes/metabolismo , Canales de Sodio/metabolismo , Animales , Axones/metabolismo , Axones/ultraestructura , Membrana Celular/ultraestructura , Desnervación , Pez Eléctrico , Electrofisiología , Inmunohistoquímica , Microscopía Electrónica , Vaina de Mielina , Regeneración Nerviosa , Neuroma/ultraestructura , Neuronas Aferentes/ultraestructura , Canales de Sodio/ultraestructuraRESUMEN
Reed et al described the clinical and light-microscopic findings of palisaded encapsulated neuromas in 1972, but few cases have been reported since. We have studied 81 consecutive tumors. Clinically, these were solitary, asymptomatic, 2- to 6-mm, flesh-colored papules, usually located on the face of middle-aged patients. The correct diagnosis was rarely made; the lesion was most often mistaken for a basal cell epithelioma, melanocytic nevus, or other benign tumor. Light microscopy revealed single or multiple encapsulated dermal lobules composed of interlacing Schwann cells. Variable numbers of fine axons and myelin sheath remnants were present. Palisading of nuclei was not a prominent feature. Electron microscopy demonstrated substantial numbers of class C fibers (mostly nonmyelinated) only partially enveloped by Schwann cell cytoplasm. Pathologically, palisaded encapsulated neuromas are distinctive true neuromas resembling those seen in the multiple mucosal neuroma syndrome. Electron-microscopic findings are similar to those seen in peripheral nerve regeneration, suggesting that palisaded encapsulated neuromas may be traumatic in origin, and could represent regeneration following local minor injury to the skin.
Asunto(s)
Neuroma/patología , Neoplasias Cutáneas/patología , Adulto , Diagnóstico Diferencial , Neoplasias Faciales/patología , Femenino , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Neuroma/etiología , Neuroma/ultraestructura , Células de Schwann/ultraestructura , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/ultraestructuraRESUMEN
A case report of multiple mucosal neuroma syndrome (multiple endocrine adenomatosis type 3) is presented in a mother and her two children. In all of them the eye involvement consisted of highly visible corneal nerves, neuromas of the conjunctiva, and thickened eye lids. The mother had mucosal neuromas of the tongue, and in the 4-year-old girl these were seen to appear during the follow-up period. The mother and children had medullary carcinoma of the thyroid. Marfanoid physiognomy was also one characteristic clinical feature.