TNF-alpha and phosphorylation of ERK in DRG and spinal cord: insights into mechanisms of sciatica.
METHODS
Characterize extracellular signal-regulated kinase (ERK) and its phosphorylation (pERK) in neural tissues after topical application of tumor necrosis factor-alpha (TNF-alpha) to L5 nerve root.


OBJECTIVE
Identify time-course, localization, and expression of pERK.


BACKGROUND
TNF-alpha has a key role in disc herniation and sciatica as an inflammatory component of the nucleus pulposus. ERK is associated with neuronal signal transduction and nociception.


METHODS
We studied tissue from naive rats, vehicle-treated rats, and rats receiving rat recombinant TNF-alpha using Western blots of total and phosphorylated ERK (pERK). We used immunohistochemistry of pERK with neuronal nuclear (NeuN) antibody to identify its cellular distribution.


RESULTS
Topical application of TNF-alpha to rat nerve root increased pERK in ipsilateral dorsal root ganglion (DRG) neurons and glia within 5 hours. pERK was not expressed in DRG during the first hour after TNF-alpha application, nor was it seen at anytime in spinal cord dorsal horn. DRG satellite cells had increased pERK 5 hours after TNF-alpha or vehicle treatment. TNF-alpha treatment increased pERK in small- and medium-sized DRG neurons and to a lesser degree in large neurons.


CONCLUSIONS
These findings suggest that ERK signaling plays a role in the activation of DRG cells following inflammatory injuries to nerve roots and further documents the importance of inflammation in the pathogenesis of painful spine disorders.
Takahashi
Naoto
N
Department of Anesthesiology, University of California, School of Medicine, San Diego, CA, USA.
Kikuchi
Shinichi
S
Shubayev
Veronica I
VI
Campana
W Marie
WM
Myers
Robert R
RR
D000287:Administration, Topical; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012585:Sciatica / Q000209:etiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases