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

A nociceptive role for tumor necrosis factor-alpha (TNF-alpha) in naive mice and in mice with fibrosarcoma tumor-induced primary hyperalgesia was investigated. The presence of TNF-alpha mRNA was confirmed in tumor site homogenates by reverse transcription-polymerase chain reaction (RT-PCR), and examination of TNF-alpha 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-alpha 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-alpha can excite or sensitize primary afferent fibers to mechanical stimulation in both naive and tumor-bearing mice. In addition, the hyperalgesia produced by TNF-alpha was completely eliminated when the injected TNF-alpha 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-alpha may contribute to tumor-induced nociception.