Challenges and opportunities in translational pain research – An opinion paper of the working group on translational pain research of the European pain federation (EFIC)

Abstract

For decades, basic research on the underlying mechanisms of nociception has held promise to translate into efficacious treatments for patients with pain. Despite great improvement in the understanding of pain physiology and pathophysiology, translation to novel, effective treatments for acute and chronic pain has however been limited, and they remain an unmet medical need. In this opinion paper bringing together pain researchers from very different disciplines, the opportunities and challenges of translational pain research are discussed. The many factors that may prevent the successful translation of bench observations into useful and effective clinical applications are reviewed, including interspecies differences, limited validity of currently available preclinical disease models of pain, and limitations of currently used methods to assess nociception and pain in non‐human and human models of pain. Many paths are explored to address these issues, including the backward translation of observations made in patients and human volunteers into new disease models that are more clinically relevant, improved generalization by taking into account age and sex differences, and the integration of psychobiology into translational pain research. Finally, it is argued that preclinical and clinical stages of developing new treatments for pain can be improved by better preclinical models of pathological pain conditions alongside revised methods to assess treatment‐induced effects on nociception in human and non‐human animals. Significance: For decades, basic research of the underlying mechanisms of nociception has held promise to translate into efficacious treatments for patients with pain. Despite great improvement in the understanding of pain physiology and pathophysiology, translation to novel, effective treatments for acute and chronic pain has however been limited, and they remain an unmet medical need.

Investigating the Role of Ly6G+ Neutrophils in Incisional and Inflammatory Pain by Multidimensional Pain-Related Behavioral Assessments: Bridging the Translational Gap

“…The assessment of “pain” in rodents is a multidimensional approach and presently a matter of ongoing debate. Despite significant preclinical pain research efforts, a translational gap exists between pain-related outcomes in rodents and humans ( 1 ). This leads to an insufficient understanding of mechanisms of pain entities and the unsuccessful development of novel therapeutic options.…”

“…However, these assessments [still used in most preclinical pain studies (2,4,5)] are not only prone to experimental bias (6); they also encompass mainly the somatosensory (spinal reflex) pathways and miss the complex cognitive and emotional as well as voluntary components of pain. In contrast, multidimensional behavioral outcome measures in preclinical settings presumably capturing clinically relevant symptoms might improve translation (1,(7)(8)(9).…”

“…As a result, many patients suffer from acute and chronic pain as current analgesics have limited efficacy and side effects. One reason that hampers the development of new treatment options is a translational gap from basic science to the clinical situation ( 1 , 2 ). For example, there is increasing evidence for pain entity-specific mechanisms; therefore, the development and use of preclinical pain models, which more precisely represent clinical situations, are highly needed ( 1 , 3 ).…”

“…One reason that hampers the development of new treatment options is a translational gap from basic science to the clinical situation ( 1 , 2 ). For example, there is increasing evidence for pain entity-specific mechanisms; therefore, the development and use of preclinical pain models, which more precisely represent clinical situations, are highly needed ( 1 , 3 ). Further, outcome assessments in preclinical and clinical research represent a significant mismatch and are the subject of current discussion in clinical and preclinical areas ( 1 ).…”

“…For example, there is increasing evidence for pain entity-specific mechanisms; therefore, the development and use of preclinical pain models, which more precisely represent clinical situations, are highly needed ( 1 , 3 ). Further, outcome assessments in preclinical and clinical research represent a significant mismatch and are the subject of current discussion in clinical and preclinical areas ( 1 ). From a historical perspective, evoked pain-related behaviors are assessed by determining withdrawal reactions to external applied mechanical and thermal stimuli to the hindpaw of rodents.…”