Analgesics promote welfare and sustain tumour growth in orthotopic 4T1 and B16 mouse cancer models

Jennie Lofgren, Amy Miller, Claudia Lee, Carla Bradshaw, Paul Flecknell, Johnny Roughan

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Abstract

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers
were investigated in mice pre-treated with meloxicam (10 mg/kg), buprenorphine (0.2 mg/kg) or saline
(1 ml/kg). Tumours were imaged and welfare was assessed using body weight, behaviour and nociceptive
responses. In study 1, BALB/c mice were inoculated with 4T1 mammary carcinoma or saline during surgery or
anaesthesia. As pre-treatment with a single buprenorphine dose appeared beneficial to cancer growth consistency, a second cohort of mice additionally received saline or buprenorphine at 12 and 24 h. Surgery
resulted in increased mammary tumour growth and lung metastases. These unwanted effects were lessened
by buprenorphine pre-treatment, especially when given repeatedly. Mammary tumour-bearing mice became
less active and nociceptive thresholds declined over time, indicating some discomfort as tumours grew. In
study 2, C57BL/6 mice received B16 melanoma. This non-surgical model was used to determine whether
meloxicam or buprenorphine affected cancer seeding of the lungs. While meloxicam reduced B16 lung
seeding, buprenorphine did not. Mechanical thresholds decreased as cancer developed in mice bearing
melanoma, but the magnitude of this was insufficient to conclude that there were any significant welfare
concerns. This study highlights the scientific value in utilising non-surgical models, where possible. When
surgery must be performed at the time of tumour inoculation, the effects of this should be controlled with
appropriate analgesics to enhance the value and possibly translation of the research.
Original languageEnglish
Pages (from-to)351-364
JournalLaboratory Animals
Volume52
Issue number4
Publication statusPublished - 5 Dec 2017
Externally publishedYes

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