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

Satoshi Hatashita, Miho Sekiguchi, Hideo Kobayashi, Shin-ichi Konno, Shin-ichi Kikuchi
Spine 2008 May 20, 33 (12): 1344-51

STUDY DESIGN: The contralateral pain-related behavioral and immunohistochemical changes after hemilateral spinal nerve injury in rats were investigated.

OBJECTIVES: 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.

SUMMARY OF BACKGROUND DATA: 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.

CONCLUSION: 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.

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