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.