Somatostatin (SOM) is an antinociceptive peptide that is also antiangiogenic and can reduce tumor growth (Florio et al., 2003). Octreotide (OCT), a synthetic analogue of SOM, has shown analgesic properties in the treatment of cancer pain in man after intrathecal (i.t.) perfusion (Paice et al., 1996) but not after subcutaneous (s.c.) injection (Deconno et al., 1994). The aim of this study was to assess the effect of i.t. and s.c. perfusion of OCT in a rat model of bone cancer pain.

Mammary gland carcinoma cells (3000/animal) were injected in the left tibia of female Sprague Dawley rats (150-160g), under enflurane anaesthesia (Medhurst et al., 2002). Ten days after cell injection, osmotic mini pumps (7 days delivery) containing OCT (50 µg/kg/hr = 216 µg/day) or vehicle (acetate buffer pH 5) were implanted s.c. under enflurane anaesthesia. In a separate experiment, osmotic mini pumps containing OCT (3 µg/day ) or vehicle (0.1% rat serum albumin in saline) were implanted s.c. and attached to a cannulae for i.t. perfusion, under enflurane anaesthesia. Pain-related behaviour was monitored between day 10 and day 17. Static allodynia assessed by measurements of von Frey hair withdrawals and weight bearing difference between the ipsilateral and contralateral hind limb were measured on day 10, 14 and 17 after cell injection. On day 17, morphine (6mg/kg, s.c.) was injected to vehicle group (after measurement) and allodynia and weight bearing difference were assessed 1h post injection.

In both experiments 6-8 animals per group were used. Statistical analysis: ANOVA followed by Dunnett' test.

As expected, intratibial injection of tumor cells significantly reduced ipsilateral paw withdrawal thresholds from control levels of 11.6±1.2g to 7.2±1.9g (n.s.) and 4.5±1.1g (p<0.01), at days 14 and 17 post cell injection, respectively. Systemically delivered OCT produced no significant reduction in static allodynia induced by cancer cell injection (3.7±0.6 g) compared to vehicle (4.5±1.1g) on day 17. Similarly, OCT did not affect weight bearing difference (84±12 g) compared to control (73±5 g) on day 17. However, a single dose of morphine significantly reduced allodynia (15.0±0.0g vs 4.5±1.1g, p<0.001), and weight bearing difference (14.3±4.4 vs 73±5g, p<0.001). In contrast, OCT (3 µg/day i.t.) significantly reduced static allodynia (7.7±0.7 vs 3.2±0.8g, p<0.001) and weight bearing difference (33.5±3.0 vs 79.2±4.5g, p<0.001) on day 17. A single i.t. injection of OCT (0.3µg) did not affect allodynia and weight bearing difference.

These results show that the somatostatin analogue OCT can reduce the pain-related behaviours in a rat model of bone cancer. The effect of OCT might be confined centrally and not at the tumor site. These results correlate with the effect of OCT in the clinic and indicate a good predictability of the animal model for the human disease.

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