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

Although it is known that different types of nerve root insults can produce radicular pain, it is not known whether the neuronal and Schwann cell pathologies in the nerve root vary between inflammation-induced nerve root injury and traumatic compression. This study examined the extent of Wallerian degeneration and associated cellular repair processes in the nerve root in the context of mechanical hyperalgesia resulting from different modes of painful nerve root injury. The C7 dorsal nerve root underwent a transient 10 gram-force compression (10g), inflammation-induced irritation by chromic gut exposure (Cg), or a combination of those stimuli (10g + Cg). Fourteen days after injury when hyperalgesia remained, immunohistochemical analysis revealed upregulation of substance P, robust macrophage infiltration, myelin degeneration and debris removal, and a significant increase in the number of myelinating Schwann cells (Krox20-positive) in the compressed roots (10g, 10g + Cg). Cg alone also produced hyperalgesia, despite being associated with intact myelin. Unilateral exposure to chromic material induced bilateral increases in macrophages and Krox20-positive Schwann cells in the nerve roots, and substance P expression in the dorsal root ganglion (DRG) neurons. Results suggest that despite similar sensitivity, the extent of infiltrating macrophages and repopulated Schwann cells varies for pain from mechanical and/or chemical nerve root injury. Although these different cellular mechanisms may explain pain, they may also only reflect varying injury etiologies.