TNF-α and phosphorylation of ERK in DRG and spinal cord: insights into mechanisms of sciatica

N Takahashi, S Kikuchi, VI Shubayev, WM Campana… - Spine, 2006 - journals.lww.com
N Takahashi, S Kikuchi, VI Shubayev, WM Campana, RR Myers
Spine, 2006journals.lww.com
Study Design. Characterize extracellular signal-regulated kinase (ERK) and its
phosphorylation (pERK) in neural tissues after topical application of tumor necrosis factor-
alpha (TNF-α) to L5 nerve root. Objective. Identify time-course, localization, and expression
of pERK. Summary of Background Data. TNF-α 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 …
Study Design.
Characterize extracellular signal-regulated kinase (ERK) and its phosphorylation (pERK) in neural tissues after topical application of tumor necrosis factor-alpha (TNF-α) to L5 nerve root.
Objective.
Identify time-course, localization, and expression of pERK.
Summary of Background Data.
TNF-α 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-α 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-α 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-α application, nor was it seen at anytime in spinal cord dorsal horn. DRG satellite cells had increased pERK 5 hours after TNF-α or vehicle treatment. TNF-α 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.
Lippincott Williams & Wilkins