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Journal of Environmental Pathology, Toxicology and Oncology
Factor de Impacto: 1.241 Factor de Impacto de 5 años: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Imprimir: 0731-8898
ISSN En Línea: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v31.i2.80
pages 167-177

Distinct Susceptibility to Inoculated Melanoma and Sensitivity to Cancer Pain in Mouse Lines With High and Low Sensitivity to Stress

Mariusz Sacharczuk
Institute of Genetics and Animal Breeding, Polish Academy of Sciences
Agnieszka R. Ragan
Department of Molecular Cytogenetics, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland; Neuropeptide Department, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland
Hanna Szymanska
Department of Genetics and Breeding Laboratory Animals, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Anna Lesniak
Neuropeptide Department, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland
Bogdan Sadowski
Department of Molecular Cytogenetics, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
Andrzej W. Lipkowski
Neuropeptide Department, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland

SINOPSIS

Approximately 30 years ago, we developed 2 mouse lines with enhanced and decreased opioid system activity using bidirectional selection for high (high analgesia [HA] line) and low (low analgesia [LA] line) swim stress-induced analgesia. These mouse lines differ substantially in pain sensitivity, measured as hind paw withdrawal latency in a hot plate test. Moreover, compared with the LA mice, the HA mice exhibited reduced energy expenditure under stress and different depression-like behavior as well as higher sensitivity to mutagens and the high frequency of spontaneous and carcinogen-induced tumors. In the current study, we observed distinct differences in the growth rate of orthotopically implanted melanoma and the onset of cancer pain. Whereas the HA line was prone to tumors and carcinogenesis was rapid in all specimens, the LA mice either did not develop tumors (70%) or developed tumors that often regressed spontaneously (30%). Animals from both lines developed robust thermal hypersensitivity in the tumor-bearing paw compared with animals that were injected with saline. However, we found that hyperalgesia in tumor-bearing mice persists for a much shorter time in the HA than in LA mice. Naltrexone, given subcutaneously, restored hyperalgesia in the HA mice, whereas it was ineffective in the LA mice. The results suggest that activity of the opioid system may influence carcinogenesis and the intensity of cancer pain and indicates that HA and LA mice are good models for such studies.