Optimization of opioid therapy for preventing incident pain associated with bone metastases.

Breakthrough pain is a transitory flare of pain superimposed on an otherwise stable pain pattern in patients treated with opioids. One form of breakthrough pain is incident pain, which is due to movement and is commonly associated with bone metastases. The development of this pain is rapid and no medication, administered "as needed," has such a rapid onset that it parallels this temporal pattern of pain. This study used a construct based on the prevention of this event, and implemented a new experimental paradigm. Specifically, the study determined whether increasing the opioid doses above those sufficient to control pain at rest would reduce the occurrence of these pains. Twenty-five consecutive patients with movement-related episodic pain associated with bone metastases, and no evident fractures, were selected for the study. They received a rapid intravenous titration of the opioid dose to obtain pain relief at rest. Then, opioid doses were increased to challenge the therapeutic window. The dose ceiling was determined by the development of limiting adverse effects, rather than optimal pain control at rest. Opioid dose increases were then stopped, or doses were even reduced, according to patients' satisfaction or development of adverse effects with moderate-severe intensity. Basal pain intensity and pain induced by movement were measured using a numerical scale from 0-10. Opioid-related symptoms were assessed using a scale from 0 to 3 (absent, slight, moderate, severe), and global daily doses of oral morphine and other symptomatic drugs were also recorded at daily intervals, and at time of discharge, when the best balance was presumed to be reached. Basal pain control was achieved after rapid intravenous titration. The day after, pain induced by movement significantly improved using mean doses of oral morphine equivalents of 102 mg. In the following days, the subsequent increase in opioid doses prescribed despite optimal basal pain control allowed an acceptable level of incident pain intensity until patients' discharge. A minority of patients developed adverse effects with an intensity of 2-3 on the scale, requiring symptomatic treatment or decreases in opioid doses. Data from this study suggest that the intensity of incident pain may be reduced by increasing the opioid dose above that effective for controlling pain at rest. This approach is based on experimental bone models showing a hypersensitivity to some innocuous stimuli, such as movement, requiring pre-emptive higher doses of basal opioid medication to reduce the increased pain input.