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.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

BACKGROUNDDetermining the nerve of origin for vestibular schwannoma (VS), as a method for predicting hearing prognosis, has not been systematically considered. The vestibular test can be used to investigate the function of the superior vestibular nerve (SVN) and the inferior vestibular nerve (IVN). This study aimed to preoperatively distinguish the nerve of origin for VS patients using the vestibular test, and determine if this correlated with hearing preservation.

METHODSA total of 106 patients with unilateral VS were enrolled in this study prospectively. Each patient received a caloric test, vestibular-evoked myogenic potential (VEMP) test, and cochlear nerve function test (hearing) before the operation and 1 week, 3, and 6 months, postoperatively. All patients underwent surgical removal of the VS using the suboccipital approach. During the operation, the nerve of tumor origin (SVN or IVN) was identified by the surgeon. Tumor size was measured by preoperative magnetic resonance imaging.

RESULTSThe nerve of tumor origin could not be unequivocally identified in 38 patients (38/106, 35.80%). These patients were not subsequently evaluated. In 26 patients (nine females, seventeen males), tumors arose from the SVN and in 42 patients (18 females, 24 males), tumors arose from the IVN. Comparing with the nerve of origins (SVN and IVN) of tumors, the results of the caloric tests and VEMP tests were significantly different in tumors originating from the SVN and the IVN in our study. Hearing was preserved in 16 of 26 patients (61.54%) with SVN-originating tumors, whereas hearing was preserved in only seven of 42 patients (16.67%) with IVN-originating tumors.

CONCLUSIONSOur data suggest that caloric and VEMP tests might help to identify whether VS tumors originate from the SVN or IVN. These tests could also be used to evaluate the residual function of the nerves after surgery. Using this information, we might better predict the preservation of hearing for patients.

Adult ; Female ; Hearing ; Humans ; Male ; Neuroma, Acoustic ; pathology ; physiopathology ; Vestibular Nerve ; physiology

Humans ; Neoplasms, Cystic, Mucinous, and Serous ; pathology ; therapy ; Neuroma, Acoustic ; pathology ; therapy

Adult ; Female ; Humans ; Magnetic Resonance Imaging ; Neuroma, Acoustic ; pathology ; surgery

OBJECTIVETo study the clinicopathologic features of lipomatosis of nerve (NLS).

METHODSThe clinical, radiologic and pathologic features were analyzed in 15 cases of NLS.

RESULTSThere were a total of 10 males and 5 females. The age of patients ranged from 4 to 42 years (mean age = 22.4 years). Eleven cases were located in the upper limbs and 4 cases in the lower limbs. The median nerve was the most common involved nerve. The patients typically presented before 30 years of age (often at birth or in early childhood) with a soft and slowly enlarging mass in the limb, with or without accompanying motor and sensory deficits. Some cases also had macrodactyly and carpal tunnel syndrome. MRI showed the presence of fatty tissue between nerve fascicles, resembling coaxial cable in axial plane and assuming a spaghetti-like appearance in coronal plane. On gross examination, the affected nerve was markedly increased in length and diameter. It consisted of a diffusely enlarged greyish-yellow lobulated fusiform beaded mass within the epineural sheath. Histologically, the epineurium was infiltrated by fibrofatty tissue which separated, surrounded and compressed the usually normal-appearing nerve fascicles, resulting in perineural septation of nerve fascicles and microfascicle formation. The infiltration sometimes resulted in concentric arrangement of perineural cells and pseudo-onion bulb-like hypertrophic changes. The perineurial cells might proliferate, with thickening of collagen fibers, degeneration and atrophic changes of nerve bundles. Immunohistochemical study showed that the nerve fibers expressed S-100 protein, neurofilament and CD56 (weak). The endothelial cells and dendritic fibers were highlighted by CD34. The intravascular smooth muscle cells were positive for muscle-specific actin.

CONCLUSIONSNLS is a rare benign soft tissue tumor of peripheral nerve. The MRI findings are characteristic. A definitive diagnosis can be made with histologic examination of tissue biopsy.

Adolescent ; Adult ; Antigens, CD34 ; metabolism ; CD56 Antigen ; metabolism ; Carpal Tunnel Syndrome ; complications ; pathology ; Child ; Child, Preschool ; Diagnosis, Differential ; Extremities ; innervation ; Female ; Hand Deformities, Congenital ; complications ; pathology ; Humans ; Lipoma ; pathology ; Lipomatosis ; complications ; diagnosis ; metabolism ; pathology ; surgery ; Magnetic Resonance Imaging ; Male ; Median Nerve ; metabolism ; pathology ; Nerve Sheath Neoplasms ; pathology ; Neurofibroma ; pathology ; Neurofilament Proteins ; metabolism ; Neuroma ; pathology ; Peripheral Nervous System Diseases ; complications ; diagnosis ; metabolism ; pathology ; surgery ; Peripheral Nervous System Neoplasms ; pathology ; Retrospective Studies ; S100 Proteins ; metabolism ; Vimentin ; metabolism ; Young Adult

OBJECTIVE: By detecting the myelin structure in acoustic tumor tissues, the cell origin and state of acoustic tumor tissues were investigated. METHOD: Immunofluorescence labeling, immunoblot analysis and electron microscopic study were performed to identify myelin structure and myelin protein in acoustic tumor tissues. RESULT: In this work, we found some early stage of myelin forming in acoustic tumor tissues, but there were no axon nor compact myelin formed and the myelin basic protein whose expression indicates the beginning of myelination was negative detected. We also found that the cell of acoustic tumor express p75,a marker for immature Schwann cells and mature non-myelin-forming Schwann cells. CONCLUSION The date shown in this experiment indicates that the cell of acoustic tumor is in a remyelinating state.
Humans ; Microscopy, Electron ; Myelin Sheath ; pathology ; ultrastructure ; Neuroma, Acoustic ; pathology ; Schwann Cells ; pathology

BACKGROUNDThe choice for the surgical approach of interdigital neuroma in the foot is controversial. Plantar approach can leave a painful scar on weight bearing area; hence, some prefer dorsal approach. The aim of the current study was to measure the outcome of interdigital (Morton's) neurectomy performed by a single surgeon using dorsal and plantar approaches.

METHODSA retrospective review of the patient records of one orthopaedic foot and ankle surgeon identified thirty-six patients (42 feet) who had been treated operatively for a primary, persistently painful interdigital neuroma. The mean follow-up was 18 months. Pain, weight bearing, wound problems and rehabilitation period were studied.

RESULTSThe duration to full weight bearing, return to work, driving and recreational activities were at least one week shorter in the dorsal group. The overall satisfaction for surgery was rated as excellent or good in 85% of the thirty six patients. Scar problems were more troublesome and common in the plantar group. There was residual numbness noticed in twenty feet, the pattern of numbness was quite variable and it was bothersome in only seven feet. There was one recurrence in the plantar group.

CONCLUSIONSResection of a symptomatic interdigital neuroma through a dorsal or a plantar approach can result in a good outcome. Dorsal approach, however, is associated with better rehabilitation and less scar problems.

Adult ; Aged ; Female ; Foot ; pathology ; physiopathology ; surgery ; Foot Diseases ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Neuroma ; pathology ; surgery ; Retrospective Studies ; Treatment Outcome ; Weight-Bearing

Amputation neuroma or traumatic neuroma is a tumor-like secondary hyperplasia that may develop after an accidental or surgical trauma. Amputation neuroma of the bile duct has occasionally been reported which occurred in the cystic duct stump late after the cholecystectomy. However, even if the amputation neuroma is suspected in a patient with late-onset jaundice after cholecystectomy, the differential diagnosis from a malignancy is difficult preoperatively. We experienced a case of the amputation neuroma of common bile duct (CBD) developed in a 70-year-old man who presented with a polypoid mass in CBD. He had undergone cholecystectomy 25 years ago and choledochojejunostomy 12 years ago, respectively. We have performed pylorus-preserving pancreatico-duodenectomy (PPPD) under the impression of CBD cancer. He had not been diagnosed of amputation neuroma until having undergone PPPD. We report a case of CBD neuroma mimicking CBD cancer, which was confirmed after PPPD.
Aged ; Common Bile Duct Neoplasms/*diagnosis/radiography ; Diagnosis, Differential ; Humans ; Male ; Neuroma/*diagnosis/pathology/radiography ; Pancreaticoduodenectomy ; S100 Proteins/immunology ; Tomography, X-Ray Computed

Traumatic neuroma is a well-known disorder that occurs after trauma or surgery involving the peripheral nerve and develops from a nonneoplastic proliferation of the proximal end of a severed, partially transected, or injured nerve. We present a case of traumatic neuroma around the celiac trunk after gastrectomy in a 56-year-old man, which was confirmed by pathology. CT demonstrated the presence of a lobulated, homogeneous, hypoattenuating mass around the celiac trunk, mimicking a nodal metastasis.
Celiac Plexus/*pathology/surgery ; Diagnosis, Differential ; Gastrectomy ; Gastric Bypass ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasms, Post-Traumatic/*diagnosis/surgery ; Neuroma/*diagnosis/surgery ; Peripheral Nervous System Neoplasms/*diagnosis/surgery ; Positron-Emission Tomography ; Tomography, X-Ray Computed

OBJECTIVETo determine the changes of Substance P in the substantia gelatinosa of the dorsal horn field after transient liquid nitrogen freezing of severed rat sciatic nerve for prevention of terminal neuroma.

METHODSThe bilateral sciatic nerves of 20 SD rats were severed, and the left sciatic nerves was subjected to transient liquid nitrogen freezing with the right sciatic nerve as control. After 20 and 28 weeks, the nerve ends were resected and prepared for microscopic examination, and Substance P in the substantia gelatinosa of the dorsal horn field was determined by immunohistochemistry.

RESULTSTypical neuromas occurred in the severed ends of the right sciatic nerves but not in the left sciatic nerves. The distribution and optical density of Substance P in the substantia gelatinosa of the dorsal horn field was significantly smaller in the left than in the right nerves (P<0.05).

CONCLUSIONLiquid nitrogen freezing of the severed sciatic nerve results in decreased release of Substance P in the substantia gelatinosa of the dorsal horn field, suggesting that noxious stimulation may increase Substance P release in the substantia gelatinosa of the dorsal horn field.

Animals ; Cryopreservation ; methods ; Female ; Male ; Nerve Fibers ; metabolism ; pathology ; Neuroma ; metabolism ; pathology ; prevention & control ; Nitrogen ; chemistry ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; injuries ; metabolism ; pathology ; Substance P ; metabolism ; Substantia Gelatinosa ; metabolism ; pathology