The metastasis of tumours to bone is the most common cause of pain experienced by cancer patients. Metastatic tumours invade osseous tissue in 60% to 84% of all cancer cases. Cancer induced bone pain (CIBP) is generated from either the presence of primary tumours within bone or through metastasis from pre-existing cancers particularly from the prostate, breast or lung. With all current therapeutic regimes against CIBP considered, 41% of patients are left with inadequate pain control. The objectives of this study were to establish a metastatic model of CIBP and to observe related nociceptive changes in an animal model. Anaesthetized rats received per-cutaneous intra-femoral injections directly into the right hind-leg distal epiphysis to induce tumour formation. Injections comprised of MATLyLu cells, a murine prostate cancer cell line. On days 3, 7, 10 and 13 post-injection, rats were subjected to two tests for nociception namely the incapacitance test and Randall-Selitto test. These tests are classically used to observe the development of nociceptive behavioural alterations associated with tumour development. We also examined the effect of meloxicam, an anti-inflammatory agent, on the observed nociceptive behaviours in the animals. Prior to testing for nociception, rats received intraperitoneal injections of meloxicam. Groups were divided based upon meloxicam dose as follows: 5.0 mg/kg meloxicam, 2.5 mg/kg meloxicam, 1.0 mg/kg meloxicam and 5% methyl cellulose (vehicle). Following MATLyLu cell injection, rats progressively developed an aggressive tumour within the distal femoral epiphysis over a course of 13 days. Tumour development resulted in the progressive distribution of weight to the contralateral hind leg. Also, tumour development progressively reduced the force required to initiate the withdrawal response from the ipsilateral hind paw. It was observed that 5.0 mg/kg of meloxicam was capable of tapering progressive distribution of weight to the contralateral hind leg. 5.0 mg/kg meloxicam injection was also affective at maintaining the paw withdrawal threshold at base line level up to 10 days post MATLyLu cell injection. In conclusion, intra-femoral injections of MATLyLu cells result in the development of aggressive tumours that lead to nociceptive behaviours in rats. As tumour growth continues, the nociceptive behaviours become progressively enunciated. 5.0 mg/kg meloxicam demonstrated the ability to partially ameliorate observed nociceptive behaviours in rats with bone tumours. (This study was supported by the Canadian Institutes of Health Research.)

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2346.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009