Nociceptive characteristics of tumor necrosis factor-α in naive and tumor-bearing mice

P. W. Wacnik, L. J. Eikmeier, D. A. Simone, G. L. Wilcox, A. J. Beitz

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46 Scopus citations


A nociceptive role for tumor necrosis factor-α (TNF-α) in naive mice and in mice with fibrosarcoma tumor-induced primary hyperalgesia was investigated. The presence of TNF-α mRNA was confirmed in tumor site homogenates by reverse transcription-polymerase chain reaction (RT-PCR), and examination of TNF-α protein levels in tumor-bearing mice indicated a significantly higher concentration of this cytokine in tumor microperfusates and tumor site homogenates compared with that obtained from a similar site on the contralateral limb or in naive mice. Intraplantar injection of TNF-α into naive or fibrosarcoma tumor-bearing mice induced mechanical hypersensitivity, as measured by withdrawal responses evoked by von Frey monofilaments. This hypersensitivity suggests that TNF-α can excite or sensitize primary afferent fibers to mechanical stimulation in both naive and tumor-bearing mice. In addition, the hyperalgesia produced by TNF-α was completely eliminated when the injected TNF-α was pre-incubated with the soluble receptor antagonist TNFR:Fc. Importantly, pre-implantation systemic as well as post-implantation intra-tumor injection of TNFR:Fc partially blocked the mechanical hyperalgesia, indicating that local production of TNF-α may contribute to tumor-induced nociception.

Original languageEnglish (US)
Pages (from-to)479-491
Number of pages13
Issue number2
StatePublished - 2005

Bibliographical note

Funding Information:
Kristin Schreiber contributed to the preparation of this manuscript. This work was supported by NIH R01-CA84233, NIH R01-CA72669, NIH R01-CA91007 and NIH R21-CA86330 with additional support to P.W.W. by NIH/5T 32-DEO 7288–02 and to L.J.E. by National Institute on Drug Abuse training grant DA07239. Thanks to Cory Goracke, Jeremy Alley, and Autumn Kelly for behavioral testing and to Christine Baker, Marna Erickson, Cory Goracke, and Carolyn Fairbanks for support of the tissue culture facilities.


  • Bone tumor
  • Cancer pain
  • Etanercept
  • Flow cytometry
  • Hyperalgesia
  • TNF-α antagonist


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