An aligned nanofiber nerve conduit that inhibits painful traumatic neuroma formation through regulation of the RhoA/ROCK signaling pathway

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OBJECTIVE

Traumatic neuromas represent a prevalent source of neuropathic pain. As of yet, there has been no single treatment method that can guarantee permanent relief of symptoms. Although nerve-capping techniques have shown promise, their exact mechanisms remain elusive. The authors’ aim was to examine the role of the RhoA/ROCK signaling pathway in the prevention of neuroma formation after neurectomy utilizing a nerve-capping technique.

METHODS

An aligned nanofiber tube was fabricated to cap the sciatic nerve in Sprague Dawley rats. The rats (n = 60) were randomly divided into the aligned SF/P (LLA-CL) capping group (capping group, n = 20), the capping and Y-27632 (ROCK pathway inhibitor) intervention group (intervention group, n = 20), and the no-capping group (control group, n = 20). The authors undertook a comprehensive assessment of the capping group, examining the animals’ behavior, the extent of neuroma development, histology, gene and protein expression, and ultrastructural changes associated with the RhoA/ROCK signaling pathway. These findings were compared with those in the intervention and control groups.

RESULTS

The inciting injury resulted in the expression of the RhoA/ROCK signaling pathway, as well as its further upregulation in peripheral neurons. Axon outgrowth was significantly increased when RhoA/ROCK signaling pathway was suppressed. The average autotomy score in the capping group was observed to be much lower than that of the intervention and control groups. At 30 days postneurectomy, the capping group displayed no obvious neuroma formation, while a bulbous neuroma was found in the nerve stumps of both the control and intervention groups. Quantitative real-time polymerase chain reaction and the Western blot analysis demonstrated that the expression of myelin-associated glycoprotein was substantially upregulated in the capping group; in contrast, the expression of NF-200 was significantly downregulated. The expression of myosin light chain was notably lower in the intervention group, but there was no significant difference when compared with the control group (p > 0.05).

CONCLUSIONS

The RhoA/ROCK signaling pathway has emerged as a critical player in the process of traumatic neuroma formation after neurectomy. It is possible that the nerve-capping technique could generate a “regenerative brake” based on the regulation of the RhoA/ROCK signaling pathway in this event. These findings may provide concrete evidence that could help develop new strategies for the management of painful neuromas.

ABBREVIATIONS MAG = myelin-associated glycoprotein; MLC = myosin light chain; NF-200 = neurofilament 200; PNS = proximal nerve stump; ROCK = Rho-associated coiled coil-forming kinase; RT-PCR = real-time polymerase chain reaction; SD = Sprague Dawley; SDS-PAGE = sodium dodecyl sulfate–polyacrylamide gel electrophoresis; SF/P (LLA-CL) = aligned silk fibroin (SF) mixed with poly(l-lactic acid-co-ε-caprolactone) (P [LLACL]).
Article Information

Contributor Notes

Correspondence Hede Yan: The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. yanhede@hotmail.com.INCLUDE WHEN CITING Published online February 1, 2019; DOI: 10.3171/2018.9.JNS18360.Disclosures Dr. Zhou has received clinical or research support for the current study from the National Natural Science Foundation of China.
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