Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain / 神经科学通报·英文版

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.

Ictericia obstructiva por neuroma de amputación de vía biliar: Reporte de caso / Obstructive ictericia by neuroma of amputation of via biliar: Case report

Los neuromas del conducto biliar se desarrollan a partir de las fibras nerviosas simpáticas y parasimpáticas que envuelven la pared de la vía biliar. Mujer de 44 años de edad con antecedente de colecistectomía convencional seis meses previos al ingreso acude a emergencia por ictericia obstructiva de 15 días de evolución. En los estudios de imagen impresiona la presencia de una masa a nivel de las vías biliares considerándose el diagnostico de una neoplasia maligna. Por los antecedentes, ausencia de marcadores tumorales se decide realizar una biopsia percutánea sin resultados concluyente, realizándose posteriormente una intervención quirúrgica con estudio anatomo-patológico compatible con neuroma de amputación de vía biliar. El neuroma de amputación a nivel de la vía biliar es un tumor infrecuente. Puede manifestarse clínicamente como una ictericia obstructiva y suele simular a un tumor maligno de las vías biliares. El manejo quirúrgico es el tratamiento definitivo.

Neuromas of the bile duct develop from the sympathetic and parasympathetic nerve fibers that surround the wall of the bile duct. A 44-year-old woman with a history of conventional cholecystectomy six months prior to hospital admission attended emergency due to obstructive jaundice that lasted 15 days. In the imaging studies, the presence of a mass at the level of the bile ducts is considered, considering the diagnosis of a malignant neoplasm. Due to the antecedents, the absence of tumor markers, it was decided to perform a percutaneous biopsy without conclusive results, performing later a surgical intervention with anatomopathological study compatible with neuroma of biliary tract amputation. The amputation neuroma at the level of the bile duct is an infrequent tumor. It can manifest clinically as obstructive jaundice and usually simulates a malignant tumor of the bile ducts. Surgical management is the definitive treatment.

Traumatic neuroma of the penis after circumcision - Case report

Abstract Traumatic neuromas are tumors resulting from hyperplasia of axons and nerve sheath cells after section or injury to the nervous tissue1. We present a case of this tumor, confirmed by anatomopathological examination, in a male patient with history of circumcision. Knowledge of this entity is very important in achieving the differential diagnosis with other lesions that affect the genital area such as condyloma acuminata, bowenoid papulosis, lichen nitidus, sebaceous gland hyperplasia, achrochordon and pearly penile papules.

Perineurioma esclerosante: relato de caso e revisão da literatura / Sclerosing perineurioma: case report and literature review

O perineurioma esclerosante é uma neoplasia benigna rara,constituída exclusivamente por células com diferenciação perineural, dispersas em meio a estroma fibroso denso. Acomete preferencialmente a pele dos quirodáctilos e das regiões palmares e se apresenta como pápula ou nódulo firme, normocrômico e assintomático. Apresentamos um caso de perineurioma esclerosante localizado na região palmar esquerda de uma paciente feminina de 16 anos de idade, com detalhada demonstração dos aspectos clínicos, histopatologia e revisão da literatura publicada em língua inglesa.

Sclerosing perineurioma is a rare benign neoplasm composed exclusively of perineural differentiation cells spread in a dense fibrous stroma. It affects primarily the skin of fingers and that of the palm of the hands. It appears as a hard papule or nodule, normochromic and asymptomatic. A case of sclerosing perineurioma in the left palm of a 16-year-old female is described, with detailed demonstration of clinical aspects, histopathology and literature review published in the English language.

Traumatic neuroma of the lower lip / Neuroma traumático del labio inferior

Traumatic neuroma is a rare disorder that represents a reactive proliferation of neural tissue following damage to an adjacent nerve. Clinically, oral lesions usually appear as a nodule of normal or grayish white smooth surface colouration, and patients may complain of pain as a frequent symptom. We report a case of a painless lower lip traumatic neuroma, clinically misdiagnosed as lipoma, in a 24-year old Caucasian woman. On intraoral examination, a yellowish and smooth sessile, well-delimited, painless, nodular lesion measuring 10 mm x 7 mm x 4 mm in size was observed on the mucosal lower lip. An excisional biopsy was performed and the final diagnosis was traumatic neuroma. After 18 months of follow-up, the patient is asymptomatic and there are no signs of recurrence.

El neuroma traumático es un trastorno raro que consiste en una proliferación reactiva del tejido neural tras producirse un daño en un nervio adyacente. Clínicamente, las lesiones orales normalmente aparecen como un nódulo de coloración normal o blanca grisácea, de superficie lisa, y los pacientes pueden quejarse de dolor como síntoma frecuente. Reportamos el caso de un neuroma traumático del labio inferior labio sin dolor, clínicamente mal diagnosticado como lipoma, en una mujer blanca de 24 años. En el examen intraoral, se observó una lesión nodular amarillenta, sésil, lisa, bien delimitada, e indolora, que medía 10 mm x 7 mm x 4 mm de tamaño, en la mucosa del labio inferior. Se realizó una biopsia, y el diagnóstico final fue un neuroma traumático. Después de 18 meses de seguimiento, el paciente se halla asintomático y no hay ninguna señal de recurrencia.

Mucosal neuromas and prominent corneal nerves without MEN IIB.

Multiple endocrine neoplasia type II B or the mucosal neuroma syndrome is an autosomal dominant hamartoneoplastic syndrome. This is a report of a 17 year old female who presented with mucosal neuromas at age 7 years and had surgical excision of the lesion. Ten years later (at age 17 years) she had further recurrence of mucosal neuromas which were again surgically excised. She has been thoroughly investigated & followed, however to date she has no evidence of thyroid carcinoma which is a major complication of this syndrome.

Pacinian neuroma

Neural tumors composed of Pacinian corpuscles are rare and have only occasionally been reported in the literature. All such lesions, which have been reported to date, have been benign. One such lesion described here presented as a painful lesion on the right hand in a 17-year-old Omani female. There was history of trap door injury 7 years back involving the wrist, thumb and index finger. The patient gradually developed multiple bosselated nodules near the first web space with gradually increasing pain. This case is being reported for the first time in the Sultanate of Oman. We herein report this case due to its rarity

Neuroma apendicular (obliteración fibrosa) asociado a microcarcinoide solitario / Neuroma of the appendix (fibrous obliteration) associated with solitary microcarcinoid

Informamos un caso de neuroma apendicular (obliteración fibrosa de la punta) asociado con microcarcinoide solitario del tercio medio del apéndice cecal. Esta lesión resulta de la proliferación neuromatosa con obliteración de la luz e hiperplasia de células endócrinas extraepiteliales. La inmunohitoquímica para proteína S-100, enolasa neurona específica (NSE) y factor de crecimiento epidérmico (EGF) resultaron positivos y la desmina, el antígeno epitelial de membrana (EMA) y la proteína fibrilar ácida glial (GFAP) fueron negativos. Lo anterior indica que la obliteración fibrosa del apéndice cecal es una proliferación de células de Schwann y no un proceso fibroblástico degenerativo. La hiperplasia de células endócrinas podría estimular por un lado, la proliferación de células de Schwann y por otro, inducir el crecimiento de carcinoides y así explicar esta interesante asociación

Histological changes in reptilean spinal cord transection: correlation with functional recovery.

The study of spinal cord regeneration in the phylogenetic scale is likely to help us in the understanding of the problem in the human situation. After spinal transection in lizards, histological changes in the spinal cord were studied and correlated with functional recovery. Some changes in spinal cord, suggestive of regeneration between the two stumps were observed. The recovery of function did not appear to be dependent on synaptic continuity.

Pseudo-polidactilia: una variedad clínica de neuromas / Pseudo-polydactyly: a clinic variety of neuromas

Se comunican tres casos de pseudo-polidactilia que corresponden a tumoraciones congénitas asintomáticas en el tercio proximal del borde ulnar de uno o ambos dedos meñiques. Histológicamente son semejantes a neuromas y es probable que correspondan a neuromas postamputación de verdaderos dedos supernumerarios autoamputados in utero. Los verdaderos dedos supernumerarios presentan falanges e histológicamente no se observa proliferación neural.

Multiple mucosal neuromatosis.

Four children aged 3 months to 14 years presenting with multiple mucosal neuromatosis (MMN) and having medullary carcinoma of the thyroid (MCT) along with various other associated features are reported. All patient had screening test for pheochromocytoma. Thyroid gland and Neuromatous growths were subjected to histological examination for confirmatory diagnosis. All patients were subjected to total thyroidectomy with removal of regional lymph nodes. They were evaluated periodically for a variable post-operative period at 2 to 4 years. The first degree relatives were also screened. One of the four children had left sided pheochromocytoma which responded satisfactorily to the adrenalectomy. Prophylactic total thyroidectomy with annual/biannual critical review to detect recurrence is advocated. It is recommended that first degree relatives of familial MMN Syndrome should also be subjected to annual screening in view of its autosomonal dominant transmission.