Opiates such as morphine are the cornerstone medications for the treatment of moderate to severe pain. Recent evidence suggests that pain patients on chronic opioid therapy become more sensitive to pain (hyperalgesia) over time. There is also a long-standing notion that analgesic tolerance to opioids (habituation) develops during chronic use even though this phenomenon has never been prospectively studied. Our specific aims propose to prospectively test the hypotheses that; 1) Pain patients on chronic opioid therapy develop dose-dependent tolerance and/or hyperalgesia to these medications over time, 2) Opioid-induced tolerance and hyperalgesia develop differently with respect to various types of pain, 3) Opioid-induced hyperalgesia occurs independently of withdrawal phenomena, and 4) Opioid-induced tolerance and hyperalgesia develop differently based on gender and/or ethnicity. This proposed study will be the first quantitative and prospective study of tolerance and hyperalgesia in pain patients and will have important implications for the rational use of opioids in the treatment of chronic pain.

Inclusion Criteria:

• opioid naïve (or less than 4 vicodin equiv/day)
• 18-70 years old
• candidate for opioid therapy for nonmalignant pain.

Exclusion Criteria:

• history of substance abuse or severe psychiatric disease
• use of medications for the treatment of neuropathic pain as these may alter tolerance or hyperalgesia
• neurological conditions interfering with experimental pain testing, e.g. severe peripheral neuropathy