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.
Hatashita
Satoshi
S
Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. hatashi@fmu.ac.jp
Sekiguchi
Miho
M
Kobayashi
Hideo
H
Konno
Shin-ichi
S
Kikuchi
Shin-ichi
S
D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001522:Behavior, Animal; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000473:pathology; D010147:Pain Measurement; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley; D027161:Satellite Cells, Perineuronal / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013127:Spinal Nerves / Q000601:surgery; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha