Discovery and Development of New Pain Medicines: Towards Improving Translational Research Outcomes

In the last two decades, an enormous global research effort directed at enhancing our collective understanding of the neurobiology of chronic pain has identified a vast array of receptors, enzymes and ion channels as potential novel targets for the development of a new generation of highly efficacious and well-tolerated analgesic medications. However, translation of this wealth of new knowledge from basic science into novel therapeutics for improving the pharmacological management of chronic pain in the clinical setting has proven challenging. Although many drug candidates in development fail due to toxicity/poor tolerability, poor pharmaceutical properties and/or unsuitable pharmacokinetics, lack of efficacy relative to placebo in proof-of-concept analgesic clinical trials, is a major factor contributing to the difficulties in research translation in the novel pain therapeutics field. One aspect of this translational challenge is the inadequacy of the rodent pain models used widely for efficacy profiling of new molecules from pain therapeutics discovery. Hence, adoption of a more sophisticated approach to efficacy profiling using a panel of new/refined rodent pain models that more closely mimic individual human pain conditions together with improved reported on side-effects, is recommended as a means to identify novel compounds more likely to show efficacy above placebo in proof-of-concept clinical trials.