The overall goal of this application is to further knowledge about the neural mechanisms of chronic pain. Recent studies have shown that patients with chronic pain have abnormal functional connectivity of the default mode network (DMN) [5,12, 14], a group of brain regions associated with freethinking, compared to healthy controls during resting-state. These group differences have been attributed to mechanisms of pain processing, however there are a number of potential confounds to this conclusion. Participants are typically instructed not to think about anything in particular, leading to unstandardized thought processes and, consequently, ambiguity in data interpretation. Few studies, however, have examined whether a participant's specific behavioral or cognitive state, such as mood or increased attention to clinical pain, contributes to this atypical connectivity. Because negative mood has been hypothesized to increase individuals'attention to somatic sensations [48], it is possible that there is a relationship between these neural processes in the experience of chronic pain. More research is needed to examine how these mental states influence brain activity during resting-state in the experience of chronic pain [8, 9, 10]. The proposed work will attempt to decompose the relationship between certain behavioral variables and brain activity during this paradigm.
The Specific Aims of this NRSA are to 1) examine the effects of positive and pain-related negative mood on functional connectivity of the DMN and 2) examine the temporal relationship between pain-related attentional and affective neural processes during resting-state. With the findings from this research, we hope to provide useful information to the interpretation of resting-state data in chronic pain patients. Additionally, we hope to disentangle the temporal relationship of attentional and affective processes in the perception of clinical pain, which will help inform treatment development.

Public Health Relevance

Chronic pain is a complex phenomenon, involving cognitive, affective, and sensory processes. The onset, course, and perception of chronic pain are often idiosyncratic, which presents difficulty in diagnosis and treatment. As such, many of these patients experience comorbid psychological conditions, interference with daily functioning, and overall reduced quality of life. The goal of the proposed project is to better understand the effects of mood on the neural mechanisms of chronic pain when patients are not engaged in goal-directed activity, with the ultimate objective of informing conventional, alternative, and complementary treatments.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZAT1)
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Khalsa, Partap Singh
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University of Florida
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Schools of Public Health
United States
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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
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
Letzen, Janelle E; Sevel, Landrew S; Gay, Charles W et al. (2014) Test-retest reliability of pain-related brain activity in healthy controls undergoing experimental thermal pain. J Pain 15:1008-14