title: 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.
abstract: 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.
authors.affiliation: Department of Anesthesiology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72211, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Homma
authors.forename: Sorin J
authors.initials: SJ
authors.lastname: Brull
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Zhang
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept