Pathogenic Hydrogel? A Novel-Entrapment Neuropathy Model Induced by Ultrasound-Guided Perineural Injections.

Ming-Yen Hsiao,Po-Ling Kuo,Chueh-Hung Wu,Ya-Wen Wu,Yu-Ling Lin,Wen-Shiang Chen

doi:10.3390/ijms22073494

Abstract

Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression–edema–ischemia cascade and perineural adhesion that results in excessive shear stress during motion. Despite decades of research, an easily accessible and surgery-free animal model mimicking the mixed etiology is currently lacking, thus limiting our understanding of the disease and the development of effective therapies. In this proof-of-concept study, we used ultrasound-guided perineural injection of a methoxy poly(ethylene glycol)-b-Poly(lactide-co-glycoilide) carboxylic acid (mPEG-PLGA-BOX) hydrogel near the rat’s sciatic nerve to induce EN, as confirmed sonographically, electrophysiologically, and histologically. The nerve that was injected with hydrogel appeared unevenly contoured and swollen proximally with slowed nerve conduction velocities across the injected segments, thus showing the compressive features of EN. Histology showed perineural cellular infiltration, deposition of irregular collagen fibers, and a possible early demyelination process, thus indicating the existence of adhesions. The novel method provides a surgery-free and cost-effective way to establish a small-animal model of EN that has mixed compression and adhesion features, thus facilitating the additional elucidation of the pathophysiology of EN and the search for promising treatments.

Highlights

Entrapment neuropathy (EN) is a prevalent and debilitative condition that causes pain, sensory impairment, and muscle atrophy in severe cases [1]
11 rats were used in the experiment
US imaging demonstrated perineural delivery of hydrogel, which appeared as homogeneous hypoechoic immediately postinjection, distributed both superficially and at deep sciatic nerve locations (Figure 1)

Summary

Introduction

Entrapment neuropathy (EN) is a prevalent and debilitative condition that causes pain, sensory impairment, and muscle atrophy in severe cases [1]. Previously-used animal models can be classified into chemical and mechanical methods. Hypertonic dextrose or a proinflammatory agent is injected perineurally to induce inflammation and subsequent fibrosis [5,6]. Injection of hypertonic dextrose in the forepaws of rabbits has been used as a research model of carpal tunnel syndrome, the most common type of EN [5,6]. Being highly similar to the human carpal tunnel structurally, the rabbit model has potential for clinical translation. Inflammation is not a key feature in EN, in which degeneration of myelin and perineural fibrosis mark the change [3,7]. Multiple injections are required to induce obvious histology changes, partly attributed to brief injectate retention after injection. An injectate that can stay in situ after injection may be more suitable for the development of this model

Methods

Results

Discussion

Conclusion