Endogenous Tumor Necrosis Factor α (TNFα) Requires TNF Receptor Type 2 to Generate Heat Hyperalgesia in a Mouse Cancer Model

• DOI: 10.1523/jneurosci.4476-07.2008
• Publication Date: 2008-05-07T17:32:25Z
• Authors: Cristina E. Const...; Norbert Mair; Claudia A. Sailer; Manfred Andratsch; Zhen-Zhong Xu; Michael J. F. Blumer; Nadja Scherbakov; John B. Davis; Horst Bluethmann; Ru-Rong Ji; Michaela Kress
• Keywords: Nociceptor

To provide a tool to investigate the mechanisms inducing and maintaining cancer-related pain hyperalgesia, soft tissue tumor/metastasis model was developed that is applicable in C57BL/6J wild-type transgenic mice. We show experimental tumor-induced heat hyperalgesia nociceptor sensitization were prevented by systemic treatment with tumor necrosis factor α (TNFα) antagonist etanercept. In naive mice, exogenous TNFα evoked vivo sensitized nociceptive nerve fibers vitro . enhanced expression of nociceptor-specific transducer ion channel transient receptor potential vanilloid 1 (TRPV1) increased amplitudes capsaicin heat-activated ionic currents via p38/MAP (mitogen-activated protein) kinase PKC (protein C). Deletion type 2 (TNFR2) gene attenuated TRPV1 upregulation tumor-bearing whereas TNFR1 deletion played minor role. propose endogenous as key player generates TNFR2.