Research Paper

Reinstatement of pain-related brain activation during the recognition of neutral images previously paired with nociceptive stimuli

Forkmann, Katarina; Wiech, Katja; Sommer, Tobias; Bingel, Ulrike

^aDepartment of Neurology, Essen University Hospital, Essen, Germany

^bFMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

^cOxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom

^dDepartment of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Corresponding author. Address: Department of Neurology, Essen University Hospital, Hufelandstr. 55, 45147 Essen, Germany. Tel.: +49 201 7232364; fax: +49 201 7236882. E-mail address: [email protected] (K. Forkmann).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Received September 20, 2014

Received in revised form April 08, 2015

Accepted April 09, 2015

PAIN 156(8):p 1501-1510, August 2015. | DOI: 10.1097/j.pain.0000000000000194

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Remembering an event partially reactivates cortical and subcortical brain regions that were engaged during its experience and encoding. Such reinstatement of neuronal activation has been observed in different sensory systems, including the visual, auditory, olfactory, and somatosensory domain. However, so far, this phenomenon of incidental memory has not been explored in the context of pain. In this functional magnetic resonance imaging study, we investigated the neural reinstatement of pain-related and tone-related activations during the recognition of neutral images that had been encoded during (1) painful stimulation, (2) auditory stimulation of comparable unpleasantness, or (3) no additional stimulation. Stimulus-specific reinstatement was tested in 24 healthy male and female participants who performed a visual categorization task (encoding) that was immediately followed by a surprise recognition task. Neural responses were acquired in both sessions. Our data show a partial reinstatement of brain regions frequently associated with pain processing, including the left posterior insula, bilateral putamen, and right operculum, during the presentation of images previously paired with painful heat. This effect was specific to painful stimuli. Moreover, the bilateral ventral striatum showed stronger responses for remembered pain-associated images as compared with tone-associated images, suggesting a higher behavioral relevance of remembering neutral pictures previously paired with pain. Our results support the biological relevance of pain in that only painful but not equally unpleasant auditory stimuli were able to “tag” neutral images during their simultaneous presentation and reactivate pain-related brain regions. Such mechanisms might contribute to the development or maintenance of chronic pain and deserve further investigation in clinical populations.