Characterization of neuromas in peripheral nerves and their effects on heterotopic bone formation
| Autor: | Jordan Minarelli, Eleanor L. Davis, Julio Mejia, Austin Dickerson, Zbigniew Gugala, Alan R. Davis, William C Moore, Elizabeth A. Olmsted-Davis |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Bone Morphogenetic Protein 2 Adrenergic beta-3 Receptor Agonists Cell Line neuroinflammation 03 medical and health sciences Cellular and Molecular Neuroscience Mice Neuroma 0302 clinical medicine Tubulin medicine otorhinolaryngologic diseases Animals peripheral nerve injury Neuroinflammation business.industry Nerve injury medicine.disease Flow Cytometry Immunohistochemistry Sciatic Nerve Axons Rats 030104 developmental biology Anesthesiology and Pain Medicine heterotopic ossification Receptors Adrenergic beta-3 Neuropathic pain Peripheral nerve injury Molecular Medicine Heterotopic ossification Sciatic nerve sense organs Schwann Cells nerve injury medicine.symptom business 030217 neurology & neurosurgery Research Article |
| Zdroj: | Molecular Pain |
| ISSN: | 1744-8069 |
| Popis: | The formation of neuromas involves expansion of the cellular components of peripheral nerves. The onset of these disorganized tumors involves activation of sensory nerves and neuroinflammation. Particularly problematic in neuroma is arborization of axons leading to extreme, neuropathic pain. The most common sites for neuroma are the ends of transected nerves following injury; however, this rodent model does not reliably result in neuroma formation. In this study, we established a rodent model of neuroma in which the sciatic nerve was loosely ligated with two chromic gut sutures. This model formed neuromas reliably (∼95%), presumably through activation of the neural inflammatory cascade. Resulting neuromas had a disorganized structure and a significant number of replicating cells. Quantification of changes in perineurial and Schwann cells showed a significant increase in these populations. Immunohistochemical analysis showed the presence of β-tubulin 3 in the rapidly expanding nerve and a decrease in neurofilament heavy chain compared to the normal nerve, suggesting the axons forming a disorganized structure. Measurement of the permeability of the blood-nerve barrier shows that it opened almost immediately and remained open as long as 10 days. Studies using an antagonist of the β3-adrenergic receptor (L-748,337) or cromolyn showed a significant reduction in tumor size and cell expansion as determined by flow cytometry, with an improvement in the animal's gait detected using a Catwalk system. Previous studies in our laboratory have shown that heterotopic ossification is also a result of the activation of neuroinflammation. Since heterotopic ossification and neuroma often occur together in amputees, they were induced in the same limbs of the study animals. More heterotopic bone was formed in animals with neuromas as compared to those without. These data collectively suggest that perturbation of early neuroinflammation with compounds such as L-748,337 and cromolyn may reduce formation of neuromas. |
| Databáze: | OpenAIRE |
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