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• W1926156811 endingPage "38" @default.
• W1926156811 startingPage "3028" @default.
• W1926156811 abstract "Tumor necrosis factor-alpha (TNF) is upregulated after nerve injury, causes pain on injection, and its blockade reduces pain behavior resulting from nerve injury; thus it is strongly implicated in neuropathic pain. We investigated responses of intact and nerve-injured dorsal root ganglia (DRG) neurons to locally applied TNF using parallel in vivo and in vitro paradigms. In vivo, TNF (0.1-10 pg/ml) or vehicle was injected into L5 DRG in naive rats and in rats that had received L5 and L6 spinal nerve ligation (SNL) immediately before injection. In naive rats, TNF, but not vehicle, elicited long-lasting allodynia. In SNL rats, subthreshold doses of TNF synergized with nerve injury to elicit faster onset of allodynia and spontaneous pain behavior. Tactile allodynia was present in both injured and adjacent uninjured (L4) dermatomes. Preemptive treatment with the TNF antagonist etanercept reduced SNL-induced allodynia by almost 50%. In vitro, the electrophysiological responses of naive, SNL-injured, or adjacent uninjured DRG to TNF (0.1-1000 pg/ml) were assessed by single-fiber recordings of teased dorsal root microfilaments. In vitro perfusion of TNF (100-1000 pg/ml) to naive DRG evoked short-lasting neuronal discharges. In injured DRG, TNF, at much lower concentrations, elicited earlier onset, markedly higher, and longer-lasting discharges. TNF concentrations that were subthreshold in naive DRG also elicited high-frequency discharges when applied to uninjured, adjacent DRG. We conclude that injured and adjacent uninjured DRG neurons are sensitized to TNF after SNL. Sensitization to endogenous TNF may be essential for the development and maintenance of neuropathic pain." @default.
• W1926156811 created "2016-06-24" @default.
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• W1926156811 creator A5051987492 @default.
• W1926156811 creator A5069589143 @default.
• W1926156811 date "2003-04-01" @default.
• W1926156811 modified "2023-10-17" @default.
• W1926156811 title "Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-alpha after spinal nerve ligation." @default.
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• W1926156811 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6742101" @default.
• W1926156811 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12684490" @default.
• W1926156811 hasPublicationYear "2003" @default.
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