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A new concept of nerve capping - peripheral nerve reinnervation into adipose tissue wrapping with collagen epineural device for prophylaxis and management of neuromas
Minghao Zheng, MD, PhD, FRCPath
1; David Gamble, MD
2; Priya Kaluskar, BSc
2; Monica Zheng, MD
3; Alex O'Brerine, MD
2; Jaslyn Cullen, Bsc
2; David M. Brogan, MD
4; Richard Carey Smith, MD
21The University of Western Australia, Perth, Western Australia, Australia; 2University of Western Sydney, Perth, Western Australia, Australia; 3Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; 4Washington University School of Medicine, St. Louis, MO
Hypothesis
Painful neuroma is common due to peripheral nerve injury and amputation. Adipose tissue contains abundant palmitoyl ethanolamide (PEA) and oleoyl ethanolamide (OEA), that have been shown modulate the altered C-fibre activation and the inflammatory process. Exposure to these fatty acids also regulate myelination and inflammation in Schwann cells. We hypothesised that PEA and OEA may inhibit axon growth and protect myelination and thus that peripheral nerve reinnervated into adipose tissue (PNRIa) with capping may be effective for treatment of painful neuroma. Here we have reported the preclinical invitro study on the effect of PEA and OEA on human Sh-Sy5Y cells (Neuroblastoma cells) and the surgical technique and clinical outcome of using PNRIa with capping by a collagen based epineural barrier structure.
Method
PEA and OEA were tested for their effect on the differentiation of ShySy5y cells and Schwann cells RSC96. MTT analysis, myelin-associated genes and axon extension were analysed. In human clinical study, we conducted peripheral nerve reinnervation into adipose tissue with capping (PNRIa) in three patients. After neurolysis, the neuroma or pre-amputated nerve in acute cases was transected and laid on epineural collagen membrane. Within the surgical field an appropriate region of subcutaneous adipose tissue is identified. The adipose tissue is prepared with gentle dissection to create a pocket and the capped nerve ending is buried, ensuring a tension-free result.
Results
PEA and OEA inhibit differentiation of shysy5y cells. The inhibition led to the suppression of neurite extension from the cell bodies of the neuronal cells. We speculated that the inhibition of neurite extension can help prevent neuroma formation due to the tangling of unguided neurite growth. In three patients who underwent the PNRIa with capping they have shown good recovery with no symptoms indicative of neuroma formation. The patient who had a symptomatic neuroma experienced an improvement in pain with decreased Pain VAS score from 100 to 30, DN4 neuropathic pain score 8/10 to 0/10, and a significant improvement across all aspects of the Elliot neuroma score. For patients who underwent the procedure as a preventative measure following complex amputation, the mean Pain VAS score was 62.5/100, mean DN4 score was 3.5/10, and post-operative Elliot neuroma scores were satisfactory.
Summary Points
A novel peripheral nerve reinnervated into adipose tissue (PNRIa) is developed for treatment of painful neuroma in patient with amputation.
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