Fixed-dose combinations for emerging treatment of pain

Pain is a large and growing medical need that is not currently being fully met, primarily due to the shortcomings of existing analgesics (insufficient efficacy or limiting side-effects). Better outcomes might be achieved using a combination of analgesics. The ratio of the combinations matters and should therefore be evaluated using rigorous quantitative and well-documented analysis.

Advances have been made in understanding the normal physiology of pain processing, including the pathways and neurotransmitters involved. Insight has also been gained about physiological processes that can lead to different 'types' of pain and the transition from acute to chronic pain conditions. This 'multimechanistic' nature of most pains is better matched using a 'multimechanistic' rather than 'monomechanistic' analgesic approach. Such an approach - and the experimental design and data analysis to assess optimal combinations - is described and discussed.

There are sound pharmacologic, as well as practical, reasons for using combinations of drugs to treat pain. Compared with single agents, they offer a potential better match to the underlying pain physiology and thus greater efficacy or reduced side effects. The optimal efficacy and side-effect ratio must be determined in a scientifically rigorous manner.