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Cell Mol Neurobiol. 2019 Mar 8. doi: 10.1007/s10571-019-00666-8. [Epub ahead of print]

Characterization of Cancer-Induced Nociception in a Murine Model of Breast Carcinoma.

Author information

1
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.
2
Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense (Unesc), Criciúma, SC, 88006-000, Brazil.
3
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.
4
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.
5
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil. gabriela.trevisan-santos@ufsm.br.
6
Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense (Unesc), Criciúma, SC, 88006-000, Brazil. gabriela.trevisan-santos@ufsm.br.
7
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Avenida Roraima, 1000, Building 21, Room 5207, Santa Maria, RS, 97105-900, Brazil. gabriela.trevisan-santos@ufsm.br.

Abstract

Severe and poorly treated pain often accompanies breast cancer. Thus, novel mechanisms involved in breast cancer-induced pain should be investigated. Then, it is necessary to characterize animal models that are reliable with the symptoms and progression of the disease as observed in humans. Explaining cancer-induced nociception in a murine model of breast carcinoma was the aim of this study. 4T1 (104) lineage cells were inoculated in the right fourth mammary fat pad of female BALB/c mice; after this, mechanical and cold allodynia, or mouse grimace scale (MGS) were observed for 30 days. To determine the presence of bone metastasis, we performed the metastatic clonogenic test and measure calcium serum levels. At 20 days after tumor induction, the antinociceptive effect of analgesics used to relieve pain in cancer patients (acetaminophen, naproxen, codeine or morphine) or a cannabinoid agonist (WIN 55,212-2) was tested. Mice inoculated with 4T1 cells developed mechanical and cold allodynia and increased MGS. Bone metastasis was confirmed using the clonogenic assay, and hypercalcemia was observed 20 days after cells inoculation. All analgesic drugs reduced the mechanical and cold allodynia, while the MGS was decreased only by the administration of naproxen, codeine, or morphine. Also, WIN 55,212-2 improved all nociceptive measures. This pain model could be a reliable form to observe the mechanisms of breast cancer-induced pain or to observe the efficacy of novel analgesic compounds.

KEYWORDS:

Allodynia; Bone metastasis; Cannabinoid; NSAIDs; Opioids; WIN 55,212-2

PMID:
30850915
DOI:
10.1007/s10571-019-00666-8

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