Abstract
Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future.
Highlights
Compressive neuropathy is common in traumatic peripheral nerve disease [1]
In order to investigate the neuropathy after nerve compression and decompression, we first validated the timing of constriction injury, followed by nerve decompression, to recapitulate the clinical neurolysis operation
Mechanical allodynia was persistently presented in the CCI 1 week group, demonstrating that irreversible damage was induced by 1 week of nerve constriction injury (Figure 1C)
Summary
Compressive neuropathy is common in traumatic peripheral nerve disease [1]. For example, is the most common compressive neuropathy of the upper extremities, with a prevalence of approximately 5% [2,3]. When the peripheral nerves undergo local compression, initial neurogenic symptoms of neuropathic pain develop, including paresthesia and dysesthesia, resulting in tingling, numbness, and burning sensations for patients of carpal tunnel syndrome. If the external compression forces persist, subsequent muscle weakness and atrophy will gradually develop with time, increasing in severity [4]. With the increase in local compression forces, ischemia of the surrounding connective tissue and nerves might trigger a subsequent cascade of nerve damage and prolonged neuroinflammation [5,6]. The entire peripheral nervous system experiences extensive neuropathology, including proximal neuronal cell damage and distal Wallerian degeneration [8]
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