Neuroimaging of pain: advances and future prospects.

UNLABELLED: Chronic pain conditions remain a high unmet medical need, and a significant number of patients are not effectively treated with currently available therapies. There is a significant challenge in developing more effective therapies to treat pain, particularly in chronic debilitating pain conditions such as neuropathic pain. Preclinical research has been beneficial in advancing mechanistic understanding of the pathophysiology of pain as well as in defining new therapeutic targets for intervention. However, the increased understanding of the neurobiology of pain has not yet translated into breakthroughs in pain therapies. Some debate exists as to how predictive the common animal models of pain are to the human condition. Translation animal model activity promises to be enhanced by application of novel neuroimaging technologies. It is well acknowledged throughout the industry that the application of preclinical to clinical translational biomarkers is an important strategy that holds promise in increasing the confidence in the translatability of the preclinical to clinical data. Imaging biomarkers have tremendous potential for affecting pain research from both diagnostic as well as therapeutic standpoints. Noninvasive imaging has the inherent advantage of being able to evaluate central mechanisms of pain and the effects of intervention both in animals and in humans. Because each subject serves as its own control, the inherent intersubject variabilities can be less of a confound. This review discusses both the promise and limitations of using imaging modalities to study pain processing and integrates it into the evolving drug discovery and development paradigm. Each section summarizes current clinical reports and, if applicable, preclinical translational findings. Emphasis is given to technical areas for future development and revealing neuroinflammation dynamics and targets that are influenced by genetics and cellular insults. With continued application of neuroimaging technologies, new therapeutic approaches to treat chronic pain as well as define tools to assess functional outcomes promise to emerge. PERSPECTIVE: This review discusses the promises and limitations of using noninvasive imaging modalities to study pain processing and integrates it into the evolving drug discovery and development paradigm. Emerging neuroimaging technologies may spawn new therapeutic approaches to treat chronic pain as well as define translational tools to assess functional clinical outcomes.