Project 170474

Pain is a major public health problem affecting one-third of the population and costing $165 billion/year in North America alone. Individual pain-relievers provide incomplete relief and can often produce troubling side effects. It has been suggested that combining different kinds of pain-relievers may improve effectiveness and reduce side effects. Some drug combinations have been proven better than each of their components alone. However, this theory has been tested for very few specific drug combinations. Studies show that, on their own, the antidepressant drug, nortriptyline, and the opioid drug, morphine, partially relieve pain due to nerve disease. The main objective of this grant proposal is to determine whether using a combination of these two drugs relieves pain more effectively and/or causes less side effects than when using either drug alone. This objective will be met by conducting a clinical trial in diabetic patients with pain due to nerve disease. The research plan involves a double-blind, randomized crossover trial which compares chronic oral administration of a nortriptyline/morphine combination to single-agent nortriptyline or morphine in patients with painful diabetic neuropathy. During each of these treatment periods, drug dosage will be gradually increased to the highest possible dose, yet a dose which produces only minimal side effects. We expect to determine whether this combination is more beneficial than either drug alone. Future research using these methods will allow for the testing of other analgesic combinations for pain management.

crossover trial design with gradual dose titration