Grant: Project Grant

Chronic pain, including neuropathic pain (NP), affects 1 in 3 Canadians and costs ~$650 billion/year in North America. Current therapies have limited efficacy and dose-limiting adverse effects (AEs). Rational combination therapy with different NP drugs has shown potential for measurable improvements in pain relief, quality of life and healthcare utilization. Today, >50% of NP patients concurrently receive 2 or more analgesics but combination use is based on little evidence. Research is urgently needed to identify safer, more effective, combinations. The goal of this research program is to identify optimal combination treatment strategies that improve outcomes in chronic pain. Our previous CIHR trials showed superiority of combinations of sedating agents - morphine+gabapentin (NEJM 2005), gabapentin+nortriptyline (Lancet 2009) and nortriptyline+morphine (Pain 2015). However, additive benefit was submaximal because these agents have similar AEs and doses must be reduced during combination therapy to ensure safety and tolerability. Thus, we hypothesize superiority of analgesic combinations that contain at least one non-sedating agent because of additive pain relief but non-additive AEs. Pregabalin (PGB), a sedating anticonvulsant, is proven effective for NP and the antioxidant, alpha-lipoic acid (ALA), is the only non-sedating systemic agent proven effective for NP. We will conduct a clinical trial to compare a PGB-ALA combination to monotherapy for NP. We expect that a PGB-ALA combination will be superior to monotherapy and this difference will be greater than with combinations of 2 sedating agents. Our core expertise comes from a closely functioning multidisciplinary team with proven excellence in chronic pain assessment/treatment, trial design, biostatistics, psychometrics and knowledge translation. Our recently funded CIHR SPOR Network in Chronic Pain will provide opportunities for confirmatory trials and knowledge translation across Canada and beyond.