Verification of Animal Pain Models by Reverse Translation

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Background

In drug discovery the mantra of “kill early, kill often” refers to identifying false leads and ending investment on those leads as quickly as possible. At each step of the drug development process a company invests millions of dollars on a potential therapeutic agent, yet agents frequently fail due to lack of efficacy in human trials. Tens of millions of dollars and thousands of person hours are committed to developing the agent with nothing to show for the investment. The losses from failed agents contribute substantially to the overall cost of successful therapies. Thus, an early demise for ineffective potential drugs or therapies is important for improving the efficiency and cost effectiveness of therapeutic development. Most pain drug discovery programs adopt an animal model for screening novel agents that is believed to mimic a human disease. Demonstrating efficacy in these models is expected to predict efficacy in humans, allowing investigators to terminate experiments on ineffective agents early in the development process. The failure of animal pain models to be predictive can be related to pathological and mechanistic differences between the model and the disease, differences in the physiology/pharmacology of the species, dissimilar pharmacokinetics, or methodological issues with the assay used in conjunction with the model.

These translational animal models are often poorly vetted for the human disease understudy and even when an agent shows promise in the model but fails in clinical trials the model is not abandoned. Just as a novel therapeutic agent is subjected to “kill early, kill often” an animal model should also be removed from the development program as early as possible. Thus, reverse translational studies on animal models should be performed to determine how well the models line up with the targeted human disorders. Failure of the model to match the disease should result in the dismissal of the model from the drug development pipeline.

In this Research Topic, which will comprise both Original Research articles and Reviews, we invite researchers to discuss reverse translation of both animal and cell models of human pain disorders for the purpose of better defining the parameters for a successful and efficient preclinical therapeutic screening program for pain.

Keywords: Reverse translation, animal models, pain disorder, pain

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