[Effects of morphine on cancer pain and tumor growth and metastasis]

Management of pain is a great problem in patients with cancer. Morphine is a principal axis in drug therapy of pain, especially at the end stage of cancer. We developed an animal model of cancer pain and examined the effects of morphine on cancer pain and tumor growth and metastasis. Orthotopic inoculation of B16-BL6 melanoma cells into the hind paw of B16BL/6 mice produced hyperalgesia and spontaneous pain-like behavior; moderate hyperalgesia was apparent on day 7-10 post-inoculation(early phase), and the hyperalgesia became severe from day 14 post-inoculation(late phase). Morphine inhibited hyperalgesia on the both phases, but higher doses were needed on the late phase. When morphine at analgesic doses was administered daily from day 16 post-inoculation, tolerance was developed for analgesia after the sixth administration. Such morphine administration of morphine suppressed tumor growth and metastasis. Sciatic neurectomy, which was performed to block the pain signaling from the tumoral tissue, also suppressed tumor growth and metastasis. Management of cancer pain may be important not only to quality of life but also to cancer treatment itself.