Optimizing the early phase development of new analgesics by human pain biomarkers

Abstract

Human pain biomarkers are based on standardized acute activation of pain pathways/mechanisms and quantitative assessment of the evoked responses. This approach can be applied to healthy volunteers, to pain patients, and before and after pharmacological interventions to help understanding and profile the mode of action (proof-of-concept) of new and existing analgesic compounds. Standardized stimuli of different modalities can be applied to different tissues (multimodal and multi-tissue) for profiling analgesic compounds with respect to modulation of pain transduction, transmission, specific mechanisms and processing. This approach substantiates which specific compounds may work in particular clinical pain conditions. Human pain biomarkers can be translational and may bridge animal findings in clinical pain conditions, which in turn can provide new possibilities for designing more successful clinical trials. Biomarker based proof-of-concept drug studies in either volunteers or selected patient populations provide inexpensive, fast and reliable mechanism-based information about dose–efficacy relationships. This is important information in the early drug development phase and for designing large expensive clinical trials.

Keywords::

• analgesics
• biomarkers
• drug screening
• experimental pain
• human pain biomarkers
• pain assessment
• proof-of-concept
• QST
• translational pain research

Financial & competing interests disclosure

Lars Arendt-Nielsen has been an advisor for Allergan, Astellas, Cephalon, Galderma, Gedeon Richter, Grünenthal, GSK, Johnson & Johnson, Lilly, Lundbeck, Merck, Mundipharma, Neurosearch, Nycomed, ONO, Sosei, Pierre-Fabre, Purdue, Sanofi, UCB and Vertex. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.