Chronic pain represents a significant public health concern, affecting over 100 million adults, and accounting for over $600 billion US annually. Current treatments for chronic pain lack efficacy, and opioid treatments have led to a significant misuse, addiction, and secondary public health crisis. We have shown that endogenous pain modulation, in the form of ?placebo? manipulations have a now well-defined neural underpinning, suggestive of descending pain modulation within and perhaps from the brain to lower nervous system. Our work has identified placebo as a potentially acceptable intervention for patients with chronic pain either as a method to enhance existing treatments, or perhaps as a stand-alone treatment. To date, the contribution of spinal cord mechanisms to placebo analgesia has been largely speculative. We propose to investigate specific hypotheses about both brain and spinal cord mechanisms, and their interactions to a model of placebo analgesia through the use of functional magnetic resonance imaging (FMRI). The neural imaging of the spinal cord is an innovative new approach heretofore not feasible for the investigation of placebo mechanisms. We will combine this new approach with our previously published, and well articulated placebo manipulation and experimental design that will allow us to investigate the relative contribution of brain and cord mechanisms in placebo analgesia. We will employ both traditional fMRI, as well as functional connectivity analyses to investigate relationships among a priori regions of interest in the brain and the spinal cord. Our innovative research design, previously employed with only brain imaging, will allow for the investigation of more centrally dependent mechanisms, vs. those that are more peripheral nervous system dependent. Our team of investigators has all the necessary expertise in chronic pain, pain processing, quantitative sensory testing, neuroimaging, and experimental design to successfully accomplish the aims proposed in this application. We have repeatedly shown our ability to successfully recruit participants for the proposed design, and have successfully employed all the procedures, either in peer reviewed publications, or as demonstrated in our preliminary studies. One critical finding from our previous work has shown that the acceptability of placebo interventions is the empirical support and understanding of the mechanisms of placebo. Thus, in addition to developing a complete understanding of the mechanisms of placebo that might results in new treatment approaches, being able to describe these mechanisms to the public, pain practitioners, and to patients will increase the acceptability of them in clinical practice, thus improving pain treatment.

Public Health Relevance

Chronic pain represents a major public health burden, affecting over 100 million Americans with an annual cost of over $500 billion. Recent findings have shown that placebo is phsysiologically active, and a powerful means of reducing pain. This project is designed to further our understand of brain, and spinal cord mechanisms of placeb-related pain control. Understanding these mechanisms will enable us to better use them in the treatment of chronic pain.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT001424-13
Application #
9937663
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Belfer, Inna
Project Start
2003-03-15
Project End
2022-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
13
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Florida
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Letzen, Janelle E; Robinson, Michael E (2017) Negative mood influences default mode network functional connectivity in patients with chronic low back pain: implications for functional neuroimaging biomarkers. Pain 158:48-57
Wager, Tor D; Woo, Choong-Wan (2016) Reply. Pain 157:1576-7
Letzen, Janelle E; Boissoneault, Jeff; Sevel, Landrew S et al. (2016) Test-retest reliability of pain-related functional brain connectivity compared with pain self-report. Pain 157:546-51
Kisaalita, Nkaku R; Hurley, Robert W; Staud, Roland et al. (2016) Placebo Use in Pain Management: A Mechanism-Based Educational Intervention Enhances Placebo Treatment Acceptability. J Pain 17:257-69
Robinson, Michael; Boissoneault, Jeff; Sevel, Landrew et al. (2016) The Effect of Base Rate on the Predictive Value of Brain Biomarkers. J Pain 17:637-41
Sevel, Landrew S; Letzen, Janelle E; Staud, Roland et al. (2016) Interhemispheric Dorsolateral Prefrontal Cortex Connectivity is Associated with Individual Differences in Pain Sensitivity in Healthy Controls. Brain Connect 6:357-64
Letzen, Janelle E; Boissoneault, Jeff; Sevel, Landrew S et al. (2016) What reliability can and cannot tell us about pain report and pain neuroimaging. Pain 157:1575-6
Sevel, Landrew S; Craggs, Jason G; Price, Donald D et al. (2015) Placebo analgesia enhances descending pain-related effective connectivity: a dynamic causal modeling study of endogenous pain modulation. J Pain 16:760-8
Sevel, Landrew S; O'Shea, Andrew M; Letzen, Janelle E et al. (2015) Effective connectivity predicts future placebo analgesic response: A dynamic causal modeling study of pain processing in healthy controls. Neuroimage 110:87-94
Robinson, Michael E; O'Shea, Andrew M; Craggs, Jason G et al. (2015) Comparison of machine classification algorithms for fibromyalgia: neuroimages versus self-report. J Pain 16:472-7

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