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Pain is not the most frequent symptom in cancer patients, but it is considered the most serious and threatening symptom. Opioid analgesics are the mainstay for analgesic treatment of cancer patients. Methadone is increasingly being considered as an alternative to morphine and seems to become relatively more potent with increasing exposure to other opioids. "Newer" side effects of opioids have been demonstrated, including cognitive impairment, generalized allodynia/hyperalgesia, myoclonus and hallucinations. When the pain relief effects of oral opioids have been exhausted, other pain management approaches, including spinal delivery of analgesics, may be effective alternatives.