Axotomy-induced up-regulation of tumor necrosis factor-alpha in the dorsal root ganglia.
OBJECTIVE
Neuropathic pain is a chronic pain syndrome associated with drug, injury or disease-induced damage or destruction of sensory afferent fibers of the dorsal root ganglia (DRG). Although the exact underlying pathologic mechanisms are not known, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) are recognized as potential modulators of peripheral and central nervous system inflammatory responses. They play a crucial role in injury and the pathologic development of chronic pain syndromes such as neuropathic pain.


METHODS
Twenty-four rats were divided into a naive control (n=6), sham (surgery exposing sciatic nerve, n=6), and peripheral nerve lesion group (unilateral axotomy of sciatic nerve, n=12).


RESULTS
The results of this study demonstrate a transient up-regulation of TNF-alpha expression within ipsi- and contralateral DRG following complete unilateral sciatic nerve axotomy as confirmed by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR. Elevated expression of TNF-alpha was noted to occur within the first 7 days post-axotomy, which subsequently normalized to baseline levels by day 14. This transient up-regulation was also associated with a switch in cellular source from predominant satellite cell expression at baseline to that involving satellite cells and abundant numbers of sensory neurons.


CONCLUSIONS
These results support the role of TNF-alpha in the upstream cascade of cellular events involved in the underlying pathogenesis of neuropathic pain. Strategies targeting the early attenuation of TNF-alpha within the DRG during the first week post-injury may have significant clinical impact in preventing the downstream cascade of events involved in the underlying cellular pathology of neuropathic pain.
Miao
Pinhui
P
Faculty of Pharmacy, University of Manitoba, Winnipeg, Man., Canada.
Madec
Kim
K
Gong
Yuewen
Y
Shen
Hong
H
Eisenstat
David
D
Melanson
Maria
M
Gu
Xiaochen
X
Leong
Christine
C
Klowak
Meghann
M
Namaka
Michael
M
D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy / Q000379:methods*; D005260:Female; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000209:etiology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha