Increased Sensitivity of Sensory Neurons to Tumor Necrosis Factor α in Rats With Chronic Compression of the Lumbar Ganglia

Liu, Baogang; Li, Huiqing; Brull, Sorin J.; Zhang, Junming

doi:10.1152/jn.2002.88.3.1393

Cited by 88 publications

(56 citation statements)

References 31 publications

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“…The observed lack of calciumpermeable AMPA/KA receptor involvement in maintenance of secondary mechanical allodynia may be due to a decrease in membrane receptor density caused by clathrin-mediated endocytosis (Lin et al, 2000). Previous electrophysiological studies demonstrate that calcium-permeable AMPA receptors rapidly internalize after their activation (Liu and Cull-Candy, 2000;Liu et al, 2002). Receptor, or receptor subunit, cycling in and out of the postsynaptic membrane (Lissin et al, 1999) may very well shift the level of calcium-permeable AMPA receptor involvement.…”

Section: Discussionmentioning

confidence: 99%

Calcium-Permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors Mediate Development, but Not Maintenance, of Secondary Allodynia Evoked by First-Degree Burn in the Rat

Jones

Sorkin²

2004

J Pharmacol Exp Ther

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Intrathecal pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists blocks development of spinal sensitization in a number of pain models. In contrast, secondary mechanical allodynia evoked by thermal injury (52.5°C for 45 s) applied to the hind paw of the rat is not blocked by intrathecal pretreatment with NMDA receptor antagonists. It is, however, blocked by antagonists to the non-NMDA, ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/KA) and calciumpermeable AMPA/KA receptors. These findings suggest a role for these receptors in the development of spinal sensitization. The present study used the same thermal injury model to assess the effects of the AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and specific calcium-permeable AMPA/KA receptor antagonists philanthotoxin (PHTx) and joro spider toxin (JST) when given as postinjury treatments. Intrathecal saline injection at 5 and 30 min postinjury had no effect on thermal injury-evoked allodynia as measured by calibrated von Frey filaments. In contrast, 36 nmol of CNQX given at either time point reversed allodynia. Intrathecal 13 nmol of PHTx or 9 nmol of JST (higher doses than that required for pretreatment) reversed allodynia at the 5-min time point, but neither drug was antiallodynic at the 30-min time point. Thus, secondary mechanical allodynia in this model is not maintained by calcium-permeable AMPA/KA receptors, but instead requires activation of calcium-impermeable AMPA/KA receptors. This finding supports a role for AMPA/KA receptor function in responses occurring during spinal sensitization.Peripheral inflammation and tissue injury induce sensitization of spinal cord neurons and enhance spinal nociceptive transmission (Dickenson and Sullivan, 1987;Abram and Yaksh, 1994;Traub, 1997). Behavioral correlates of spinal sensitization include secondary mechanical allodynia, an increased sensitivity to innocuous stimuli in a region adjacent to or distinct from the site of injury. Activation of N-methyl-D-aspartate (NMDA) receptors and subsequent calcium influx are thought to be early and necessary steps in the induction of spinal sensitization and resultant enhanced pain states (Murray et al., 1991;Mao et al., 1992;Yamamoto and Yaksh, 1992b). Accordingly, intrathecal administration of NMDA receptor antagonists has been shown to block both electrophysiological and behavioral manifestations of spinal sensitization (Woolf and Thompson, 1991;Dougherty et al., 1992). It is now apparent, however, that ␣-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid or kainite (AMPA/KA) receptors can also play a significant role in this stage of nociceptive processing.The AMPA receptor is composed of GLUR1-GLUR4 subunits, whereas the kainite receptor is composed of GLUR5-GLUR7, KA1, and K2 subunits. Both are permeable to monovalent sodium and potassium ions (Keinanen et al., 1990) and mediate the majority of monosynaptic current produced by glutamate release from primary afferent terminals. Recent studies show that ac...

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Section: Discussionmentioning

confidence: 99%

Calcium-Permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors Mediate Development, but Not Maintenance, of Secondary Allodynia Evoked by First-Degree Burn in the Rat

Jones

Sorkin²

2004

J Pharmacol Exp Ther

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“…؉ currents Previous studies have reported that TNF␣ can evoke action potentials and increase discharge rates when applied locally to nociceptive neurons (Sorkin et al, 1997;Junger and Sorkin, 2000;Sorkin and Doom, 2000;Liu et al, 2002). The mechanisms underlying this alteration in firing are not known, and we hypothesized that this effect of TNF␣ might be mediated in part by modulation of TTX-R Na ϩ channels.…”

Section: Tnf␣ Enhances Ttx-r Namentioning

confidence: 96%

Acute p38-Mediated Modulation of Tetrodotoxin-Resistant Sodium Channels in Mouse Sensory Neurons by Tumor Necrosis Factor-α

Jin¹,

Gereau²

2006

J. Neurosci.

437

373

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Tumor necrosis factor-␣ (TNF␣) is a proinflammatory cytokine involved in the development and maintenance of inflammatory and neuropathic pain conditions. TNF␣ can have long-lasting effects by regulating the expression of a variety of inflammatory mediators, including other cytokines and TNF␣ itself. However, the speed with which TNF␣ induces tactile and thermal hypersensitivity suggests that transcriptional regulation cannot fully account for its sensitizing effects, and some recent findings suggest that TNF␣ may act directly on primary afferent neurons to induce pain hypersensitivity. In the present study, we show that peripheral administration of TNF␣ induces thermal hypersensitivity in wild-type mice but not in transient receptor potential vanilloid receptor TRPV1 Ϫ/Ϫ mice. In contrast, TNF␣ produced equivalent mechanical hypersensitivity in TRPV1 Ϫ/Ϫ mice and wild-type littermates, suggesting a role for TRPV1 in TNF␣-induced thermal, but not mechanical, hypersensitivity. Because tetrodotoxin (TTX)-resistant Na ϩ channels are a critical site of modulation underlying mechanical hypersensitivity in inflammatory and neuropathic pain conditions, we tested the effects of TNF␣ on these channels in isolated mouse dorsal root ganglion (DRG) neurons. We report that acute application of TNF␣ rapidly enhances TTX-resistant Na ϩ currents in isolated DRG neurons. This potentiation of TTX-resistant currents by TNF␣ is dramatically reduced in DRG neurons from TNF receptor 1 (TNFR1) knock-out mice and is blocked by the p38 mitogen-activated protein kinase inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole]. Mechanical hypersensitivity induced by peripherally applied TNF␣ is also significantly reduced by SB202190. These results suggest that TNF␣ may induce acute peripheral mechanical sensitization by acting directly on TNFR1 in primary afferent neurons, resulting in p38-dependent modulation of TTX-resistant Na ϩ channels.

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“…In chronic constriction injury (CCI), an animal model of injury-induced painful mononeuropathy, inhibition of TNF␣ synthesis and release results in reduced pain behavior (Lindenlaub et al, 2000). In rat dorsal root ganglion (DRG), acute topical application of TNF␣ increases the firing rate of sensory neurons in normal rats and rats subjected to chronic DRG compression (Liu et al, 2002).…”

Section: Introductionmentioning

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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Increased Sensitivity of Sensory Neurons to Tumor Necrosis Factor α in Rats With Chronic Compression of the Lumbar Ganglia

Cited by 88 publications

References 31 publications

Calcium-Permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors Mediate Development, but Not Maintenance, of Secondary Allodynia Evoked by First-Degree Burn in the Rat

Calcium-Permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors Mediate Development, but Not Maintenance, of Secondary Allodynia Evoked by First-Degree Burn in the Rat

Acute p38-Mediated Modulation of Tetrodotoxin-Resistant Sodium Channels in Mouse Sensory Neurons by Tumor Necrosis Factor-α

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

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