Tumor necrosis factor-α induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions.
Tumor necrosis factor-α induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions.
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DOI：
10.1016/j.pain.2010.10.002
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发表时间：
2011-01
期刊：
影响因子：
7.4
通讯作者：
Levy D
中科院分区：
文献类型：
--
作者：
Zhang XC;Kainz V;Burstein R;Levy D
The proinflammatory cytokine TNF-alpha has been shown to promote activation and sensitization of primary afferent nociceptors. The downstream signaling processes that play a role in promoting this neuronal response remain however controversial. Increased TNF-alpha plasma levels during migraine attacks suggest that local interaction between this cytokine and intracranial meningeal nociceptors plays a role in promoting the headache. Here, using in vivo single unit recording in the trigeminal ganglia of anesthetized rats, we show that meningeal TNF-alpha action promotes a delayed mechanical sensitization of meningeal nociceptors. Using immunohistochemistry, we provide evidence for non-neuronal localization of the TNF receptors TNFR1 to dural endothelial vascular cells and TNFR2 to dural resident macrophages as well as to some CGRP-expressing dural nerve fibers. We also demonstrate that meningeal vascular TNFR1 is co-localized with COX-1 while the perivascular TNFR2 is co-expressed with COX-2. We further report here for the first time that TNF-alpha evoked sensitization of meningeal nociceptors is dependent upon local action of cyclooxygenase (COX). Finally, we show that local application of TNF-alpha to the meninges evokes activation of the p38 MAP kinase in dural blood vessels that also express TNFR1 and that pharmacological blockade of p38 activation inhibits TNF-alpha evoked sensitization of meningeal nociceptors. Our study suggests that meningeal action of TNF-alpha could play an important role in the genesis of intracranial throbbing headaches such as migraine through a mechanism that involves at least partly activation of non-neuronal TNFR1 and TNFR2 and downstream activation of meningeal non-neuronal COX and the p38 MAP kinase.
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DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA
影响因子：
2.9
作者：
Park, Soon Yong;Kim, Tae Hoon;Song, Jin-Ho
通讯作者：
Song, Jin-Ho
影响因子：
7.3
作者：
CUNHA, FQ;POOLE, S;FERREIRA, SH
通讯作者：
FERREIRA, SH
影响因子：
3.4
作者：
Parada, CA;Yeh, JJ;Levine, JD
通讯作者：
Levine, JD
DOI：
10.1073/pnas.0409225102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Cunha, TM;Verri, WA;Ferreira, SH
通讯作者：
Ferreira, SH