Contralateral neuropathic pain and neuropathology in dorsal root ganglion and spinal cord following hemilateral nerve injury in rats.

Methods: The contralateral pain-related behavioral and immunohistochemical changes after hemilateral spinal nerve injury in rats were investigated. Objective: We evaluated the longitudinal changes in contralateral mechanical allodynia, expression of tumor necrosis factor (TNF)-alpha and glial fibrillary acidic protein (GFAP)-positive satellite cells in the contralateral dorsal root ganglion (DRG), and expression of astrocytes and microglia in the contralateral spinal dorsal horn after hemilateral spinal nerve injury in rats.

Background: In previous studies, hemilateral nerve injury has sometimes induced contralateral neuropathic pain. TNF-alpha expression and glial cell reactions in the DRG and spinal cord play an important role in the neuropathic pain state, and TNF-alpha is released from glial cells in the nervous system.

Methods: Adult male Sprague-Dawley rats were used. The spinal L5 nerve distal to the DRG was crushed once for 3 seconds. At days 2, 7, 14, and 21 after surgery, mechanical allodynia was determined in bilateral hind paws by the von Frey test. Expression of TNF-alpha and GFAP in bilateral L5 DRGs and expression of GFAP and ionized calcium-binding adaptor molecule-1 (Iba-1) in bilateral L5 spinal dorsal horns were studied using immunohistochemistry and immunoblotting.

Results: Mechanical withdrawal threshold of the ipsilateral hind paw was significantly decreased for 21 days. Conversely, mechanical withdrawal threshold of the contralateral hind paw was significantly decreased from 5 to 10 g for 7 days, and was <5 g at days 14 and 21. TNF-alpha expression and GFAP-positive satellite cells in the contralateral DRG significantly increased from day 7 to day 21. In the contralateral spinal dorsal horn, GFAP-positive astrocytes significantly increased for 21 days, but Iba-1 was not significant.

Conclusions: These results suggest that contralateral mechanical allodynia induced by hemilateral spinal nerve injury is associated with upregulation of satellite cells and TNF-alpha in the contralateral DRG. In addition, our results suggest that spinal astrocytes play an important role in these contralateral changes.