In this application we argue that mechanisms of transition from acute to chronic pain critically depend on brain emotional and motivational learning and memory circuit, namely the properties of the corticostriatal system. This is a radical departure from the classic pain research tradition, which emphasizes mechanisms of nociceptive encoding and representation. We provide human and animal model data consistent with the idea, and propose unraveling underlying mechanisms and translating this information to clinical application by testing a drug treatment strategy for preventing transition to chronic pain We recruit Dr. Surmeier (a world renowned expert on the physiology and reorganization of the striatum) and Dr. Martina (a young scientist with expertise in molecular and electrophysiological studies of the brain), to collaborate with Apkarian on this project, and Drs. Fields and Zubieta act as consultants for the project.
In Aim 1 we combine the expertise of the three collaborating labs (Apkarian, Martina, Surmeier) to link large-scale brain imaging outcomes to cellular, molecular, and electrophysiological changes that we predict the corticostriatal undergoes in the transition from peripheral nerve injury to neuropathic pain-like behavior in rodents.
In Aim 2 we compare among potential drugs for preventing transition to chronic pain-like behavior in a rat model.
In Aim 3 we use the best candidate drug in a human early phase clinical trial, combined with brain imaging, for prevention of transition to chronic pain. The successful completion of the study should dramatically change current notions regarding brain mechanisms of pain chronification, and provide a new concept of treatment strategy for preventing the transition to chronic pain.

Public Health Relevance

This application is based on the idea that brain emotional and motivational learning circuitry is an integral part of the transition from acute to chronic pain. T prove this novel concept in mice and rats we combine brain imaging with cellular, molecular, and electrophysiological assays, to demonstrate the maladaptive reorganization of this system during pain chronification. Based on these observations we then test drug manipulations for preventing transition from acute to chronic pain first in rodents and then in a clinical trial with brain imaging in patients with back pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
3R01DE022746-03S1
Application #
8915433
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kusiak, John W
Project Start
2012-07-30
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60611
Apkarian, Apkar Vania (2018) Definitions of nociception, pain, and chronic pain with implications regarding science and society. Neurosci Lett :
Apkarian, A Vania; Reckziegel, Diane (2018) Peripheral and central viewpoints of chronic pain, and translational implications. Neurosci Lett :
Chang, Pei-Ching; Centeno, Maria Virginia; Procissi, Daniel et al. (2017) Brain activity for tactile allodynia: a longitudinal awake rat functional magnetic resonance imaging study tracking emergence of neuropathic pain. Pain 158:488-497
Radzicki, Daniel; Pollema-Mays, Sarah L; Sanz-Clemente, Antonio et al. (2017) Loss of M1 Receptor Dependent Cholinergic Excitation Contributes to mPFC Deactivation in Neuropathic Pain. J Neurosci 37:2292-2304
Vachon-Presseau, Etienne; Tétreault, Pascal; Petre, Bogdan et al. (2016) Corticolimbic anatomical characteristics predetermine risk for chronic pain. Brain 139:1958-70
Petre, Bogdan; Baria, Alexis T; Apkarian, A Vania (2016) Reply. Pain 157:508-9
Huang, Lejian; Kutch, Jason J; Ellingson, Benjamin M et al. (2016) Brain white matter changes associated with urological chronic pelvic pain syndrome: multisite neuroimaging from a MAPP case-control study. Pain 157:2782-2791
Davis, Don A; Ghantous, Mariam E; Farmer, Melissa A et al. (2016) Identifying brain nociceptive information transmission in patients with chronic somatic pain. Pain Rep 1:e575
Vachon-Presseau, E; Centeno, M V; Ren, W et al. (2016) The Emotional Brain as a Predictor and Amplifier of Chronic Pain. J Dent Res 95:605-12
Chang, Pei-Ching; Procissi, Daniel; Bao, Qiyuan et al. (2016) Novel method for functional brain imaging in awake minimally restrained rats. J Neurophysiol 116:61-80

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