American Society for Peripheral Nerve

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Epineural Sheath Jacket Prevents Neuroma Formation in the Rat Sciatic Nerve Model
Adam Bobkiewicz, MD1; Joanna Cwykiel, MSc2; Wojciech Francuzik, MD3; Maria Siemionow, MD, PhD, DSc1,2
1Poznan University of Medical Sciences, Poznan, Poland; 2University of Illinois at Chicago, Chicago, IL; 3Charité - Universitätsmedizin, Berlin, Germany

Background: Recent data of modern war conflicts, natural disasters and traffic accidents show an increase in the number of patients suffering from severe peripheral nerve injuries. Persistent stump pain is reported in 74% limb amputees. Furthermore, it is estimated that up to 25% of patients after limb amputation develop painful end-bulb neuromas. This study investigates the efficacy of epineural sheath jacket (ESJ) as a novel technique to prevent neuroma formation in the rat sciatic nerve model.

Methods: Eighteen Lewis rats were divided into three experimental groups (n=6): Group I– 20mm sciatic nerve segment was resected and proximal nerve stump was left without protection (positive control), Group II- nerve stump was buried into the adjacent muscle (standard for neuroma management), Group III- nerve stump protected by ESJ. The ESJ was created from the resected 20mm segment of sciatic nerve by removal of the fascicles and ligation of its distal end. Next, the ESJ was applied over the proximal sciatic nerve stump as a cap. The presence of neuropathic pain was assessed weekly up to 24 weeks post-surgery by autotomy, pinprick test and Tinel sign. At 24 weeks end-point, macroscopic evaluation, histomorphometry and neural/connective tissue ratio (N/C) were assessed. Retrograde labeling (RNL) of sensory neurons was used to evaluate Dorsal Root Ganglions (DRGs) viability.

Results: ESJ application significantly reduced neuroma formation, which was associated with decreased autotomy (16.7%, p<0.05) and Tinel sign (16.7%, p<0.05) compared to the nerve stump control. Moreover, ESJ reduced axonal sprouting, bulb–shape nerve ending formation and perineural adhesions as confirmed by macroscopic evaluation. Histological staining showed that nerve stumps protected by ESJ were less fibrotic and presented well-organized axonal architecture and lower number of inflammatory cells. N/C ratio and RNL analysis revealed significantly better results in the ESJ group compared to the stump group (p=0.032 and p=0.042, respectively).

Conclusion: The protective effect of ESJ against neuroma formation was confirmed by behavioral and histological analysis showing outcomes comparable to the muscle burying – the standard for neuroma management. ESJ inhibits neuroma development by creating a physical barrier for nerve fascicle outgrowth and limits inflammation, fibrosis and scar tissue formation around the nerve stump. The surgical technique for ESJ creation is straightforward and can be easily transferred to the clinic by applying the same principles of ESJ creation from human cadaver donor nerves. ESJ may become an off-the-shelf product, readily available for both the civilian and military patients.

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