Spinal cord compression injury in adult rats initiates changes in dorsal horn remodeling that may correlate with development of neuropathic pain

J Comp Neurol. 2009 Apr 20;513(6):668-84. doi: 10.1002/cne.21986.

Abstract

Spinal cord injury commonly causes chronic, neuropathic pain. The mechanisms are poorly understood but may include structural plasticity within spinal and supraspinal circuits. Our aim was to determine whether structural remodeling within the dorsal horn rostral to an incomplete injury differs from a complete spinal cord transection. Four immunohistochemical populations of primary afferent C-fibers, and descending catecholamine and serotonergic projections, were examined in segments T9-T12 at 2 and 12 weeks after a T13 clip-compression injury in adult male rats. Dorsal root ganglia were also examined. Two weeks after injury, fibers immunoreactive for calcitonin gene-related peptide (CGRP) or GDNF-family receptors (GFRalpha1, GFRalpha2, GFRalpha3) showed distinct injury responses within the superficial dorsal horn. CGRP fibers decreased, but GFRalpha1, GFRalpha2 and GFRalpha3 fibers did not change. In contrast, all groups were decreased by 12 weeks after injury. Catecholamine fibers showed a decrease at 2 weeks followed by an increase in density at 12 weeks, whereas serotonergic fibers showed a decrease (restricted to deep dorsal horn) at 12 weeks. These results show that the dorsal horn of the spinal cord undergoes substantial structural plasticity rostral to a compression injury, with the most profound effect being a prolonged and possibly permanent loss of primary afferent fibers. This loss was more extensive and more prolonged than the loss that follows spinal cord transection. Our results provide further evidence that anatomical reorganization of sensory and nociceptive dorsal horn circuits rostral to an injury could factor in the development or maintenance of spinal cord injury pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Area Under Curve
  • Calcitonin Gene-Related Peptide / metabolism
  • Catecholamines / metabolism
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
  • Immunohistochemistry
  • Male
  • Neuronal Plasticity / physiology
  • Pain / physiopathology*
  • Posterior Horn Cells / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Spinal Cord Compression / physiopathology*
  • Spinal Cord Injuries / physiopathology*

Substances

  • (4-serotonyl)-4-serotonin
  • Catecholamines
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Serotonin
  • Calcitonin Gene-Related Peptide