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.
Wacnik
P W
PW
Department of Pharmacology, University of Minnesota, School of Medicine, Minneapolis, MN 55455, USA.
Eikmeier
L J
LJ
Simone
D A
DA
Wilcox
G L
GL
Beitz
A J
AJ
D000818:Animals; D001522:Behavior, Animal; D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000150:complications / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000150:complications / Q000378:metabolism*; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha