1. 2014;17;465-474New Insights from Immunohistochemistry for the Characterization of Epidural Scar Tissue
   Laboratory Study
   Paulo Pereira, MD, Antonio Avelino, PhD, Pedro Monteiro, MD, Rui Vaz, MD, PhD, and Jose Manuel Castro-Lopes, MD, PhD.

BACKGROUND: The association between epidural fibrosis and recurrent symptoms after lumbar spine surgery remains a matter of debate in scientific literature and the underlying pathophysiological mechanism has not been clearly elucidated.

OBJECTIVE: To investigate the presence of nerve fibers and the expression of osteopontin in epidural fibrous tissue after lumbar surgery in humans.

STUDY DESIGN: Laboratory study of human tissue samples.

METHODS: Twenty-four patients with persistent or recurrent low back and/or leg pain after lumbar spine surgery, in whom no relevant findings were present on magnetic resonance imaging (MRI) besides epidural scar tissue, were submitted to epiduroscopy. Biopsy samples of epidural scar tissue resting in the posterior epidural and periradicular space were obtained from 15 patients, using an endoscopic grasping forceps, in locations where the stimulation with the tip of a Fogarty consistently reproduced pain. Biopsy samples were processed for examination under optical and transmission electron microscopes and under a fluorescence microscope after incubation in primary antibodies against beta3-tubulin or against osteopontin.

RESULTS: Optical and transmission electron microscopy revealed a homogeneous fibrous tissue rich in collagen and lacking nerve fibers. No immunofluorescence was present in any of the samples immunoreacted against beta3-tubulin. In the samples immunoreacted against osteopontin, a punctate signal was detected around the collagen fibers.

LIMITATIONS: Being a human study, there was no control group, so it is not possible to determine the contribution of osteopontin in the formation of epidural fibrosis and its relation to the patients’ symptoms. Additional animal studies are needed to investigate these issues.

CONCLUSION: Rather than direct stimulation of nociceptors in the epidural scar tissue, other factors should relate epidural fibrosis and recurrent symptoms after lumbar spine surgery. Osteopontin seems to play a role in the formation of epidural fibrosis.