Inflammatory and Neuropathic Pain From Bench to Bedside: What Went Wrong?

Abstract

In recent years, the disappointing history of translation in pain research has undergone significant scrutiny. The escalation of knowledge and understanding related to presumed pain in neuropathic and inflammatory animal models contrasted with the unsatisfactory record of "bench-to-bedside" translation has raised many questions about the validity and clinical relevance of preclinical models and methods of behavioral assessment. Although many opinions have been expressed one of the overriding concerns and greatest barriers to the widening gap between preclinical research and the development of new interventions has been the underappreciated distinction between pain and nociception. As a result of these shortcomings, the distance between mechanism-based research and patient-centered product development has been referred to as the "valley of death." The reasons for the disappointing record of translation are many and easy to point out, but the changes needed and the strategies necessary to accomplish translational goals are much more difficult to identify. One of the challenges of translational pain research that has garnered a lot of attention relates to strategies of behavioral assessment which, with few exceptions, has remained basically unchanged for more than 3 decades. Other issues important to the discussion include but are not limited to the predictive validity of preclinical models, and the neglect of gender, age, and comorbidities in the design of preclinical studies. On the clinical side, the lack of sanitization of phenotypes in clinical trials has also contributed to the insufficient success of efforts to translate basic research to the clinic. The current review will discuss these and other issues believed to have contributed to the existing obstacles and challenges facing pain research along with making recommendations for the future.

Perspective: In this review the challenges of preclinical pain research and the reasons for the disappointing record of translation are examined. Important to this discussion is recognizing the scope of clinical characteristics associated with chronic pain conditions and the need for more clinically relevant models and methods of pain assessment.

Keywords: Pain; animal models; behavioral assessment; nociception; translation.