A comparison of chronic pain behavior following local application of tumor necrosis factor alpha to the normal and mechanically compressed lumbar ganglia in the rat.
To study the role of inflammatory cytokines in the initiation and persistence of radiculopathy as seen in humans, tumor necrosis factor alpha (TNF-alpha) was administered either to normal, uninjured L5 dorsal root ganglia (DRG) of rats via a hole drilled through the transverse process, or to chronically compressed L5 DRG via a hollow stainless steel rod inserted into the intervertebral foramen. In other experiments, a mixture of soluble TNF receptors (sTNF-Rs: sTNF-RIplus minussTNF-RII) was locally delivered to the chronically or acutely compressed DRG to neutralize the activity of endogenous TNF-alpha. Behavioral tests of mechanical allodynia were performed before and after TNF-alpha administration. Infusion of the normal DRG with TNF-alpha at a rate of 1 microl/h for 7 days induced ipsilateral mechanical allodynia (i.e. decreased mechanical withdrawal threshold) that lasted about 2 weeks. Infusion of the compressed DRG did not alter compression-induced allodynia within the first operative week but substantially enhanced the ipsilateral allodynia after the first postoperative week. Neutralizing the activity of endogenous TNF-alpha of the compressed DRG with sTNF-Rs reduced allodynia for 3 days, but was subsequently without effect. Similar results were obtained when sTNF-Rs were chronically administrated at the acutely compressed ganglion. Results demonstrated that exogenous TNF-alpha causes pain and mechanical allodynia when deposited at the normal DRG, and further enhances the ongoing allodynia when administrated at the compressed DRG. Results also suggest that endogenous TNF-alpha contributes to the early development of mechanical allodynia in rats with chronic DRG compression.
Homma
Yuko
Y
Department of Anesthesiology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72211, USA.
Brull
Sorin J
SJ
Zhang
Jun-Ming
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D002908:Chronic Disease; D004195:Disease Models, Animal; D000068800:Etanercept; D005727:Ganglia, Spinal / Q000187:drug effects / Q000276:immunology*; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D009408:Nerve Compression Syndromes / Q000276:immunology; D009437:Neuralgia / Q000139:chemically induced / Q000276:immunology*; D011843:Radiculopathy / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept