In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 28, No. 19 ( 2008-05-07), p. 5072-5081
Kurzfassung:
To provide a tool to investigate the mechanisms inducing and maintaining cancer-related pain and hyperalgesia, a soft tissue tumor/metastasis model was developed that is applicable in C57BL/6J wild-type and transgenic mice. We show that the experimental tumor-induced heat hyperalgesia and nociceptor sensitization were prevented by systemic treatment with the tumor necrosis factor α (TNFα) antagonist etanercept. In naive mice, exogenous TNFα evoked heat hyperalgesia in vivo and sensitized nociceptive nerve fibers to heat in vitro . TNFα enhanced the expression of the nociceptor-specific heat transducer ion channel transient receptor potential vanilloid 1 (TRPV1) and increased the amplitudes of capsaicin and heat-activated ionic currents via p38/MAP (mitogen-activated protein) kinase and PKC (protein kinase C). Deletion of the tumor necrosis factor receptor type 2 (TNFR2) gene attenuated heat hyperalgesia and prevented TRPV1 upregulation in tumor-bearing mice, whereas TNFR1 gene deletion played a minor role. We propose endogenous TNFα as a key player in cancer-related heat hyperalgesia and nociceptor sensitization that generates TRPV1 upregulation and sensitization via TNFR2.
Materialart:
Online-Ressource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.4476-07.2008
Sprache:
Englisch
Verlag:
Society for Neuroscience
Publikationsdatum:
2008
ZDB Id:
1475274-8
SSG:
12
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