Objective biomarkers of pathology exist for a number of diseases, and their development is one of the great advances of modern allopathic medicine. However, objective assessment of pain and other mental health disorders has lagged far behind. Pain cannot be explained by peripheral damage alone;it is caused by a variety of neuropathological processes, which has made it difficult to assess and treat. Currently, the only acceptable way to measure pain is by self-report, which presents a serious barrier to effective research and treatment. Self-reported pain is influenced by nociceptive, affective, and cognitive decision-making processes-and though there are many treatments that can influence reported pain, they likely do so through a heterogeneous set of neurophysiological mechanisms, with different consequences for health and long-term well being. As a result, in spite of a long history of research, current treatments for pain are effective for a minority of individuals, with enormous costs to patients and to society. Biomarkers for physical pain could dramatically improve diagnosis and treatment, by allowing pain to be characterized on the basis of underlying neuropathology, rather than external symptoms. They could also improve treatment, by allowing interventions to be targeted to type of neuropathology involved. Biomarkers that can shed light on the brain pathophysiology that causes pain must necessarily rely on direct measures of brain function. In the past several years, major advances in combining functional magnetic resonance imaging (fMRI) with machine learning techniques-algorithms for finding predictive patterns in complex datasets-have brought the goal of fMRI-based pain assessment within reach. In preliminary data, we show for the first time that fMRI activity can predict whether an individual person is experiencing high or low physical pain with over 90% sensitivity and specificity. Critically, the biomarker is specific to physical pain when compared with non-painful touch and several classes of salient, affective events. In addition, it achieves this level of accuracy when applied prospectively to new samples, across different scanners and paradigms. This preliminary success raises a number of issues that must be addressed before fMRI-based biomarkers can be used in large-scale clinical trials and clinical practice, including a) robustnes across laboratories and procedures, b) specificity to body site, modality, and quality of pain, c) responses to analgesic treatment, and d) applicability to spontaneous and acute hypersensitivity/allodynia in clinical populations. Here, we propose to aggregate existing data across a consortium of researchers, allowing more extensive tests of sensitivity and specificity across 13 fMRI studies in healthy individuals and 18 studies in diverse clinical pain populations. In addition, we will conduct five new experiments to address critical aspects of biomarker performance. These data will allow us to develop and validate new, more comprehensive biomarkers that can assess multiple aspects of pain across healthy individuals and chronic pain sufferers.

Public Health Relevance

Pain affects nearly everyone at some time in their lives, with enormous costs to individuals and society. Current treatments for pain are only modestly effective, in large part because pain is created through a complex set of brain processes and can be measured only by patients'self-reports, which presents a serious barrier to effective research and treatment. This project capitalizes on recent breakthroughs in measuring human brain activity and using it to objectively assess the brain processes that underlie pain experience, which could transform the way pain is measured and new treatments are developed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA035484-02S1
Application #
8916319
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Lin, Yu
Project Start
2013-08-01
Project End
2018-03-31
Budget Start
2014-09-30
Budget End
2015-03-31
Support Year
2
Fiscal Year
2014
Total Cost
$159,996
Indirect Cost
$55,478
Name
University of Colorado at Boulder
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80303
Shackman, Alexander J; Wager, Tor D (2018) Introduction to the special issue on functional neuroimaging of the emotional brain. Neurosci Lett :
Kragel, Philip A; Koban, Leonie; Barrett, Lisa Feldman et al. (2018) Representation, Pattern Information, and Brain Signatures: From Neurons to Neuroimaging. Neuron 99:257-273
Reddan, Marianne Cumella; Wager, Tor Dessart; Schiller, Daniela (2018) Attenuating Neural Threat Expression with Imagination. Neuron 100:994-1005.e4
Shackman, Alexander J; Wager, Tor D (2018) The emotional brain: Fundamental questions and strategies for future research. Neurosci Lett :
López-Solà, Marina; Koban, Leonie; Wager, Tor D (2018) Transforming Pain With Prosocial Meaning: A Functional Magnetic Resonance Imaging Study. Psychosom Med 80:814-825
Kragel, Philip A; Kano, Michiko; Van Oudenhove, Lukas et al. (2018) Generalizable representations of pain, cognitive control, and negative emotion in medial frontal cortex. Nat Neurosci 21:283-289
Montagna, Silvia; Wager, Tor; Barrett, Lisa Feldman et al. (2018) Spatial Bayesian latent factor regression modeling of coordinate-based meta-analysis data. Biometrics 74:342-353
Koban, Leonie; Kusko, Daniel; Wager, Tor D (2018) Generalization of learned pain modulation depends on explicit learning. Acta Psychol (Amst) 184:75-84
Reiss, Philip T; Goldsmith, Jeff; Shang, Han Lin et al. (2017) Methods for scalar-on-function regression. Int Stat Rev 85:228-249
Geuter, Stephan; Koban, Leonie; Wager, Tor D (2017) The Cognitive Neuroscience of Placebo Effects: Concepts, Predictions, and Physiology. Annu Rev Neurosci 40:167-188

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