Tumor necrosis factor‐α induces substance P in sympathetic ganglia through sequential induction of interleukin‐1 and leukemia inhibitory factor

Ding, Minzhen; Hart, Ronald P.; Jonakait, G. Miller

doi:10.1002/neu.480280405

Cited by 53 publications

(20 citation statements)

References 32 publications

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“…We conclude that TNFa from these satellite cells appears to induce these neurons to synthesize neuropeptides and inflammatory agents [18]. Indeed, TNFa induces substance P (SP) [7], which along with calcitonin gene-related peptide (CGRP), is well known to be associated with neuropathic pain in rats [9]. It has been reported that DRG neurons innervating rat facet joints are immunoreactive for SP and CGRP, and that the ratios of CGRP-IR in L1 and L2 DRG neurons were significantly higher than in L3, L4, and L5 DRG in a rat model of facet joint inflammation [16].…”

Section: Fg-labeled Drg Neurons Innervating Rat L5/6 Facet Jointsmentioning

confidence: 88%

Up-regulation of TNFα in DRG satellite cells following lumbar facet joint injury in rats

et al. 2006

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Section: Fg-labeled Drg Neurons Innervating Rat L5/6 Facet Jointsmentioning

confidence: 88%

Up-regulation of TNFα in DRG satellite cells following lumbar facet joint injury in rats

et al. 2006

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“…In fact, TNF␣ is known to induce the release of SP and CGRP from peripheral terminals (Ding et al, 1995;Hua et al, 1996). Recombinant TNF␣ excites nociceptors and enhances heat-evoked release of CGRP from peripheral nerve terminals (Opree and Kress, 2000).…”

Section: Expression Of Tnfr 1 Mrna But Not Of Tnfr2 Mrna In Drg Neuronsmentioning

confidence: 99%

Cell-Specific Expression and Lipopolysaccharide-Induced Regulation of Tumor Necrosis Factor α (TNFα) and TNF Receptors in Rat Dorsal Root Ganglion

Li¹,

Ji²,

Weihe³

et al. 2004

J. Neurosci.

115

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The proinflammatory and lipopolysaccharide (LPS)-inducible cytokine tumor necrosis factor ␣ (TNF␣) has been shown to enhance primary sensory nociceptive signaling. However, the precise cellular sites of TNF␣ and TNF receptor synthesis are still a matter of controversy. Therefore, we differentiated the neuronal and non-neuronal sites of TNF␣, TNFR1, and TNFR2 mRNA synthesis in dorsal root ganglion (DRG) of control rats and evaluated how their expression is altered under systemic challenge with LPS. In situ hybridization (ISH), RT-PCR analysis of laser-microdissected cells, and immunocytochemistry revealed absence of TNF␣ from DRG neurons and LPS-induced expression of TNF␣ exclusively in a subpopulation of non-neuronal DRG cells. Using RT-PCR and Northern blotting TNFR1 and TNFR2 mRNAs were found to be constitutively expressed and increased after LPS. TNFR1 mRNA was expressed in virtually all neurons and in non-neuronal cells with increased levels after LPS in both. TNFR2 was exclusively expressed and regulated in nonneuronal cells. RT-PCR analysis of microdissected DRG neurons and of the sensory neuronal cell line F11 confirmed the neuronal expression of TNFR1 and excluded that of TNFR2. Double ISH revealed varying levels of TNFR1 mRNA in virtually all DRG neurons including putative nociceptive neurons coding for calcitonin gene-related peptide, substance P, or vanilloid receptor 1. Taken together, we provide evidence that non-neuronally synthesized TNF␣ may directly act on primary afferent neurons via TNFR1 but not TNFR2. This is likely to be relevant under conditions of inflammatory pain and infections accompanied by widespread TNF␣ synthesis and release and may drive sickness behavior.

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“…Wenn primär afferente Neurone über längere Zeit mit IL-1β behandelt werden, wird die Freisetzung von Substanz P über das COX-2-System bewirkt [51]. TNF induziert Substanz P in sympathischen Ganglien über die Induktion von IL-1 und leukemia inhibiting factor (LIF) [28]. IL-6 und LIF bewirken eine verstärkte Synthese von Galanin in sensiblen Neuronen [123].…”

Section: üBer Welche Wege Können Zytokine Bei Nervenläsionen Schmerz unclassified

Zytokine bei neuropathischen Schmerzen

Sommer¹

2001

Der Anaesthesist

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Cytokines are a heterogeneous group of polypeptides that were originally described to mediate activation of the immune system and inflammatory responses. Most of them have meanwhile been shown to be also produced by and act on the peripheral and central nervous system. There is ample evidence from experimental studies that proinflammatory cytokines induce or increase neuropathic pain as well as inflammatory pain. Direct actions of cytokines on afferent nerve fibers have been shown as well as actions involving further mediators such as prostaglandins or nerve growth factor. Inhibition of proinflammatory cytokines, either by synthesis inhibitors, inhibitors of cleavage from the cell membrane, by direct antagonists, or by anti-inflammatory antibodies, reduces pain and hyperalgesia in most models studied. Studies with cytokine knock-out animals often lead to different results from the pharmacological studies. This is in part due to compensatory mechanisms in the animals combined with the high redundancy of the cytokine system. Preliminary data from human studies are encouraging insofar as in the future, cytokine inhibition may add to the panel of treatment modalities for neuropathic pain.

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Tumor necrosis factor‐α induces substance P in sympathetic ganglia through sequential induction of interleukin‐1 and leukemia inhibitory factor

Cited by 53 publications

References 32 publications

Up-regulation of TNFα in DRG satellite cells following lumbar facet joint injury in rats

Up-regulation of TNFα in DRG satellite cells following lumbar facet joint injury in rats

Cell-Specific Expression and Lipopolysaccharide-Induced Regulation of Tumor Necrosis Factor α (TNFα) and TNF Receptors in Rat Dorsal Root Ganglion

Zytokine bei neuropathischen Schmerzen

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