Epineurial application of TNF elicits an acute mechanical hyperalgesia in the awake rat

Sorkin, Linda S.; Doom, Carmen M.

doi:10.1046/j.1529-8027.2000.00012.x

Cited by 187 publications

(104 citation statements)

References 19 publications

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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.

443

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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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.

443

373

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“…The cytokine actions may include directly producing discharge of nerve fibers. [25][26][27] The slow pathway starts with cytokine production by macrophages that can act on the circumventricular organs (CVOs) and choroid plexus surrounding brain ventricles. These regions have no blood-brain barrier.…”

Section: Preclinical Evidence Consistent With Roles For Cytokines In mentioning

confidence: 99%

Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism?

Cleeland

Bennett

Dantzer

et al. 2003

Cancer

471

340

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BACKGROUNDCancers and cancer treatments produce multiple symptoms that collectively cause a symptom burden for patients. These symptoms include pain, wasting, fatigue, cognitive impairment, anxiety, and depression, many of which co‐occur. There is growing recognition that at least some of these symptoms may share common biologic mechanisms.METHODSIn November 2001, basic and clinical scientists met to consider evidence for a cytokine‐immunologic model of symptom expression along with directions for future research.RESULTSThe characteristics of cytokine‐induced sickness behavior in animal models have much in common with those of symptomatic cancer patients. Sickness behavior refers to a set of physiologic and behavioral responses observed in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines. In some cases, these responses can be prevented by cytokine antagonists. A combination of animal and human research suggests that several cancer‐related symptoms may involve the actions of proinflammatory cytokines.CONCLUSIONSBased on the similarities between cancer symptoms and sickness behavior, the authors discussed approaches to further test the implications of the relationship between inflammatory cytokines and symptoms for both symptom treatment and symptom prevention. Cancer 2003;97:2919–25. © 2003 American Cancer Society.DOI 10.1002/cncr.11382

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“…1 Direct application of TNFa to peripheral nerve induces spontaneous electrophysiologic activity in neurons of the dorsal root ganglion (DRG), [2][3][4] and subcutaneous or epineurial application of TNFa produces nocisponsive behaviors. 5,6 A substantial body of evidence suggests that neuroimmune activation of glial cells in the dorsal horn of spinal cord results in the release of proinflammatory cytokines and plays an important role in facilitation of nociceptive neurotransmission and the development of chronic pain. [7][8][9][10] Expression of TNFa in the dorsal horn of spinal cord is increased in models of central 11 and peripheral 12 neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

HSV-mediated transfer of interleukin-10 reduces inflammatory pain through modulation of membrane tumor necrosis factor α in spinal cord microglia

et al. 2007

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To dissect the molecular basis of the neuroimmune response associated with the genesis of inflammatory (nociceptive) pain, we constructed a herpes simplex virus-based gene transfer vector to express the antiinflammatory cytokine interleukin-10 (IL-10), and used it to examine the effect of IL-10 expression in activated microglial cells in vitro, and in inflammatory pain in vivo. IL-10 reduced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and decreased the expression of full-length membrane spanning tumor necrosis factor-a (mTNFa) following lipopolysaccharide stimulation of microglia in vitro. IL-10 also reduced intracellular cleavage of mTNFa and release of the soluble cleavage product sTNFa. Similar effects on TNFa expression were observed when the cells were pretreated with a p38 MAPK inhibitor. In animals, injection of a dilute solution of formalin in the skin resulted in an increase in mTNFa in spinal dorsal horn, without detectable sTNFa. Local release of IL-10 achieved by gene transfer reduced the number of spontaneous flinches in the early and delayed phases of the formalin test of inflammatory pain. The effect of IL-10 on nocisponsive behavior correlated with a block in phosphorylation of p38 and reduced expression of 26 kDa mTNFa in spinal microglia. The results emphasize the key role played by membrane TNFa in the spinal neuroimmune response in pain caused by peripheral inflammation.

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Epineurial application of TNF elicits an acute mechanical hyperalgesia in the awake rat

Cited by 187 publications

References 19 publications

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

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

Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism?

HSV-mediated transfer of interleukin-10 reduces inflammatory pain through modulation of membrane tumor necrosis factor α in spinal cord microglia

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