Dorsal root compression produces myelinated axonal degeneration near the biomechanical thresholds for mechanical behavioral hypersensitivity

Abstract

Increased sensitivity to mechanical stimuli produced by transient cervical nerve root compression is dependent on the severity of applied load. In addition, trauma in the nervous system induces local inflammation, Wallerian degeneration, and a host of other degenerative processes leading to axonal dysfunction. Here, axonal degeneration and inflammation were assessed following transient dorsal root compression to establish a relationship between conditions for dorsal root axonal changes and those previously established for the onset and maintenance of mechanical behavioral hypersensitivity (26.3mN and 38.2mN, respectively). Compression loads were applied over a range (0-110mN) known to produce sustained behavioral hypersensitivity. CD68-and NF200-immunoreactivity, as well as axonal pathological changes, were assessed in the dorsal root to investigate the load thresholds requisite for inducing macrophage infiltration and axonal degeneration relative to those thresholds for producing the onset and persistence of behavioral hypersensitivity. Neurofilament accumulation and the depletion of NF200-immunoreactivity in the region of compressed tissue were produced for loads that produce mechanical behavioral hypersensitivity. A 50 th -percentile load threshold was determined (31.6mN) governing the onset of NF200 depletion. However, CD68-immunoreactivity was increased for nearly all loads, suggesting that macrophage recruitment may not be directly related to nerve root-mediated behavioral hypersensitivity. This study provides new evidence for thresholdmediated degenerative changes in the context of behavioral hypersensitivity following nerve root compression.

Schwann Cell Proliferation and Macrophage Infiltration Are Evident at Day 14 after Painful Cervical Nerve Root Compression in the Rat

“…Surgical procedures have been described in detail previously (Hubbard and Winkelstein, 2008;Rothman et al, 2009b;. Briefly, under inhalation isoflurane anesthesia (4% for induction, 2% for maintenance), the C7 dorsal root was exposed by a C6/C7 hemilaminectomy and partial facetectomy on the right side.…”

“…Briefly, under inhalation isoflurane anesthesia (4% for induction, 2% for maintenance), the C7 dorsal root was exposed by a C6/C7 hemilaminectomy and partial facetectomy on the right side. Compression of the C7 right nerve root was performed by applying a 10 gramforce microvascular clip (World Precision Instruments, Inc; Sarasota, FL) for 15 min (Hubbard and Winkelstein, 2008;Rothman et al, 2009b;. For the compression injury with chromic gut exposure (10g + Cg) 4 pieces of 3-0 chromic gut suture (Surgical Specialties; Reading, PA) were placed on nerve root after compression, as previously described (Rothman et al, 2009b;.…”

“…Nerve root injury caused by either its transient or sustained compression results in robust immune responses such as macrophage recruitment to the injury site (Gupta and Channual, 2006;Hubbard and Winkelstein, 2008; Departments of 1 Bioengineering and 2 Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania.…”

“…It has been well documented that neural injuries result in rapid and prolonged immune responses, including immune cell infiltration, expression of inflammatory mediators and trophic factors, and induction of signaling transduction pathways, all of which contribute to the neuropathy and pain (Marchand et al, 2005;Thacker et al, 2007;White et al, 2009). We have previously shown that macrophages are recruited to the site of injury at day 7 following different compression loads (0-110mN) to C7 nerve root (Hubbard and Winkelstein, 2008). In the present study, we directly compared macrophage responses using the same compression load (10g) with and without chromic gut exposure, and chromic gut irritation alone.…”

Riluzole effects on behavioral sensitivity and the development of axonal damage and spinal modifications that occur after painful nerve root compression

“…33,36,41,51 Sensitization of wide dynamic range (WDR) neurons, in particular, is thought to drive neuronal hyperexcitability and behavioral sensitivity after spinal cord ischemia and spinal nerve ligation. 28,48 Although increased calcitonin gene-related peptide (CGRP) and associated signaling contribute to neuronal hyperexcitability after painful neural trauma, 7,51 painful root compression decreases CGRP in the superficial dorsal horn.…”