Effects of Analgesics on Tumor Growth in Mouse Models of Prostate Cancer Bone Metastasis

Abstract

Murine models of tumor development often require invasive procedures for tumor implantation, potentially causing painor distress. However, analgesics are often withheld during implantation because of concerns that they may adversely affecttumor development. Previous studies examining the effects of analgesics on the development and metastasis of various tumorlines show that the effect of analgesics depends on the tumor line and analgesic used. A blanket statement that analgesicsaffect the general growth of tumors is not adequate scientific justification for withholding pain relief, and pilot studies orreferences are recommended for each specific tumor cell line and treatment combination. In this study, we evaluated the effects of 2 commonly used analgesics on tumor growth in 2 models of prostate cancer (PCa) bone metastasis. We hypothesized that a one-time injection of analgesics at the time of intratibial injection of tumor cells would not significantly impact tumor growth. Either C57BL/6 or SCID mice were injected subcutaneously with an analgesic (carprofen [5 mg/kg], or buprenorphine [0.1 mg/kg]) or vehicle (0.1 mL of saline) at the time of intratibial injection with a PCa cell line (RM1 or PC3, n = 10 to 11 per group). Tumor growth (measured by determination of tumor burden and the extent of bone involvement) and welfare (measured by nociception,locomotion, and weight) were monitored for 2 to 4 wk. Neither carprofen or buprenorphine administration consistentlyaffected tumor growth or indices of animal welfare as compared with the saline control for either cell line. This study adds to the growing body of literature demonstrating that analgesia can be compatible with scientific objectives, and that a decision to withhold analgesics must be scientifically justified and evaluated on a model-specific basis.