Nature medicine
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Chronic pain is a major challenge to clinical practice and basic science. The peripheral and central neural networks that mediate nociception show extensive plasticity in pathological disease states. ⋯ Recent work has yielded a better understanding of communication within the neural matrix of physiological pain and has also brought important advances in concepts of injury-induced hyperalgesia and tactile allodynia and how these might contribute to the complex, multidimensional state of chronic pain. This review focuses on the molecular determinants of network plasticity in the central nervous system (CNS) and discusses their relevance to the development of new therapeutic approaches.
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Biomarkers may be of great value in Alzheimer's disease drug development to select the most optimal drug candidates for large and expensive phase 3 clinical trials. Biomarkers will also be important to provide evidence that a drug affects the underlying pathophysiology of the disease, which, together with a beneficial effect on the clinical course, will be essential for labeling the drug as having a disease-modifying effect.
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Age-related neurodegenerative diseases are largely limited to humans and rarely occur spontaneously in animals. Genetically engineered mouse models recapitulate aspects of the corresponding human diseases and are instrumental in studying disease mechanisms and testing therapeutic strategies. ⋯ Translational failure is less the result of the incomplete nature of the models than of inadequate preclinical studies and misinterpretation of the models. This commentary summarizes current models and highlights key questions we should be asking about animal models, as well as questions that cannot be answered with the current models.