Neuroma Analysis in Humans: Standardizing Sample Collection and Documentation

The biology of symptomatic neuromas is poorly understood, particularly the factors causing pain in human neuromas. Pain presence varies among and within individuals, with some having painful and nonpainful neuromas. To bridge these knowledge gaps, our group developed a protocol for assessing neuroma pain and collecting tissue for molecular analysis. This manuscript outlines our workflow and challenges and aims to inspire other centers to share their experiences with these tissues.

For every included patient and collected nerve or bone tissue specimens, we perform a detailed chart review and a multifaceted analysis of pain and pain perception immediately before surgery. We collect patient-reported outcome measures (PROMs) on pain, function, and mental well-being outcomes at preoperative assessment and at the 6-month follow-up postoperatively. Before surgery, the patient is assessed once again to obtain an immediate preoperative pain status and identify potential differences in pain intensity of different neuromas. Intraoperatively, specimens are obtained and their gross anatomical features are recorded, after which they are stored in paraformaldehyde or frozen for later sample analyses. Postoperatively, patients are contacted to obtain additional postoperative PROMs.

A total of 220 specimens of nerve tissue have been successfully obtained from 83 limbs, comprising 95 specimens of neuromas and 125 specimens of nerves located proximal to the neuromas or from controls.

Our approach outlines the methods combining specimen collection and examination, including both macroscopic and molecular biological features, with PROMs, encompassing physical and psychological aspects, along with clinical metadata obtained through clinical teams and chart review.