Identifying biological markers of activity in human nociceptive pathways to facilitate analgesic drug development
| Autor: | Kenneth L. Casey, Rolf-Detlef Treede, Boris A. Chizh, Joel D. Greenspan, Michael I. Nemenov |
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| Rok vydání: | 2008 |
| Předmět: |
Gabapentin
Analgesic Pain Pharmacology Bioinformatics Models Biological Article Animals Humans Medicine Computer Simulation Afferent Pathways Analgesics business.industry Chronic pain medicine.disease Anesthesiology and Pain Medicine Monoamine neurotransmitter Nociception Neurology Drug development Drug Design Neurology (clinical) Animal studies business Reuptake inhibitor Biomarkers medicine.drug |
| Zdroj: | Pain. 140:249-253 |
| ISSN: | 0304-3959 |
| DOI: | 10.1016/j.pain.2008.09.024 |
| Popis: | Nearly 20% of the adult population in Europe suffers from moderate to severe chronic pain and only half receive beneficial treatment [8]. In US, 37% of younger adults and 57% of older adults suffer with pain lasting at least a year [9]. Despite the significance of this problem and advances in our understanding of pain mechanisms, the pace at which new treatments become available to chronic pain patients has been very slow. In recent decades, successful novel analgesics have been mostly found through serendipity or refinement of existing approaches (e.g., gabapentin, cyclooxygenase-2 and monoamine reuptake inhibitors). Analysis of drug development failures indicates that they occur primarily in clinical phases, and are mostly due to a lack of translation of efficacy in animal models to patients [7,22]. Although a comprehensive analysis of problems in analgesic development is beyond the scope of this review, we hypothesise that the preclinical to clinical transition can be facilitated by a rational use, in early drug development stages, of biological markers of activity in human nociceptive pathways. We also propose that such markers could have translational value if adapted for animal studies to provide efficacy measures more clinically relevant than withdrawal reflexes, see [29]. |
| Databáze: | OpenAIRE |
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