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Distinct brain systems mediate the effects of nociceptive input and self-regulation on pain

Cognitive self-regulation can strongly modulate pain and emotion. However, it is unclear whether self-regulation primarily influences primary nociceptive and affective processes or evaluative ones. In this study, participants engaged in self-regulation to increase or decrease pain while experiencing multiple levels of painful heat during fMRI imaging. Both heat intensity and self-regulation strongly influenced reported pain, but they did so via two distinct brain pathways. The effects of stimulus intensity were mediated by the Neurologic Pain Signature (NPS), an a priori distributed brain network shown to predict physical pain with over 90% sensitivity and specificity across four studies. Self-regulation did not influence NPS responses; instead, its effects were mediated through functional connections between the nucleus accumbens and ventromedial prefrontal cortex. This pathway was unresponsive to noxious input, and has been broadly implicated in valuation, emotional appraisal, and functional outcomes in pain and other types of affect. These findings provide evidence that pain reports are associated with two dissociable functional systems: nociceptive/affective aspects mediated by the NPS, and evaluative/functional aspects mediated by a fronto-striatal system.


001 regulated heat stimulation


  • Tor D. Wager
  • Jason T. Buhle
  • Mathieu Roy
  • Choong-Wan Woo

Acknowledgements and Funding:

Thanks to Asa Pingree and Namema Amendi for help with data collection. This work was funded by R01 DA027794 and R01 MH076136 (TDW), by a Fulbright Graduate Study Fellowship to CW, and by a post-doctoral scholarship from the Canadian Institutes of Health Research grant (CIHR) to MR. Matlab code implementing all analyses is available at

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Distinct Brain Systems Mediate the Effects of Nociceptive Input and Self-Regulation on Pain

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3T Philips Achieva TX scanner



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In addition to any citation requirements in the dataset summary please use the following to cite this dataset:

This data was obtained from the OpenfMRI database. Its accession number is ds000140



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Revision: 2.0.0 Date Set: Dec. 13, 2016, 2:05 a.m.


- Converted to BIDS format
- Curated dataset
- Incorporated regulate-up and regulate-down order in events files