Spinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal P-p38.
Spinal nerve ligation (SNL) results in a profound long lasting allodynia and increases in phosphorylated p38 in dorsal root ganglia (DRG) neurons and spinal cord microglia. We have previously shown that systemic etanercept, a tumor necrosis factor (TNF) antagonist, reduced allodynia by 42% and blocked SNL-induced increases in P-p38 levels in the L5 and L6 DRG, but not in the ipsilateral lumbar spinal cord. The present experiments demonstrated that intrathecal etanercept (100 microg) prevents SNL-induced increased levels of spinal P-p38. Pretreatment, but not posttreatment, with intrathecal etanercept (100 microg), given every third day, reduced mechanical allodynia by 50%. This therapeutic benefit was maintained for at least 7 days after cessation of treatment. Combined systemic and intrathecal administration of etanercept was no more effective than intrathecal treatment alone. These data imply that TNF provides the trigger for phosphorylation of p38 in both DRG neurons and spinal microglia.
Svensson
Camilla I
CI
Anesthesiology Research Labs, University of California, San Diego, La Jolla, CA 92093-0818, USA.
Schäfers
Maria
M
Jones
Toni L
TL
Powell
Henry
H
Sorkin
Linda S
LS
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D000068800:Etanercept; D005727:Ganglia, Spinal / Q000166:cytology / Q000201:enzymology; D006930:Hyperalgesia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007278:Injections, Spinal; D008026:Ligation / Q000379:methods; D008297:Male; D017628:Microglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000068800:Etanercept