The acknowledged limited utility of animal models for the identification of disease mechanisms and drug targets, and in the pre-clinical prediction of clinical efficacy of new drugs is a current topic of discussion across most therapeutic areas, including pain. There are multiple reasons for this generic translational failure, but amongst the more feasible solutions are:
Improved replication of the lesion/disease underlying pain in animalmodels; in particular better matching with the conditions in which clinical trials are conducted
Development of a more clinically relevant portfolio of painrelated outcome measures, which better reflects the range of efficacy measures employed in clinical trials
Adoption of similar standards to clinical research for experimental bias reduction and transparency in reporting of experimental methods
The latter two aspects will be discussed in the lecture: Firstly, I will describe our work in developing pain-related behavioral outcomemeasures which are ethologically relevant to the rat:Wehave adapted from the fear/anxiety field pharmacologically sensitive outcomemeasures which reflect predator avoidance behaviors (e.g. avoidance of exposed areas in the open field paradigm). We have also validated an assay of burrowing behavior, which is known to be sensitive to rodent disease. These behaviors have been validated in a number of models of traumatic and non-traumatic neuropathic pain and also, as yet to a lesser extent, in inflammatory pain. They have been shown to be appropriately responsive to clinically effective drugs.
Secondly, it is clear that the clinical research standards for experimental bias reduction and transparent methodology reporting are not generally evident in pre-clinical research across most therapeutic areas, including pain. There is evidence that when bias reducing methods are not used, or at least not reported, in pre-clinical studies there is an overestimation of the efficacy of novel drugs. The considerable advances which have been made in this regard in the stroke field will be reviewed and the case for adopting their “Good Laboratory Practice” standards for mitigation of experimental bias in animal studies of pain will be argued. Furthermore, adoption of the recently published, CONSORT-equivalent, ARRIVE reporting format for animal studies will increase not only the readers ability to ascertain the methodological quality of studies, but also empower systematic reviews of the pre-clinical literature.
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Funding: Wellcome Trust (London Pain Consortium), Innovative Medicines Initiative – EUROPAIN (European Commission and selected EFPIA members) and Derek Butler Trust.
Recommended reading
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© 2012 Scandinavian Association for the Study of Pain