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Brain substrates of reward processing and the μ-opioid receptor: a pathway into pain?

Nees, Frauke; Becker, Susanne; Millenet, Sabina; Banaschewski, Tobias; Poustka, Luise; Bokde, Arun; Bromberg, Uli; Büchel, Christian; Conrod, Patricia J.; Desrivières, Sylvane; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean-Luc; Papadopoulos Orfanos, Dimitri; Paus, Tomáš; Smolka, Michael N.; Walter, Henrik; Whelan, Rob; Schumann, Gunter; Flor, Hertathe IMAGEN consortium

doi: 10.1097/j.pain.0000000000000720
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The processing of reward and reinforcement learning seems to be important determinants of pain chronicity. However, reward processing is already altered early in life and if this is related to the development of pain symptoms later on is not known. The aim of this study was first to examine whether behavioural and brain-related indicators of reward processing at the age of 14 to 15 years are significant predictors of pain complaints 2 years later, at 16 to 17 years. Second, we investigated the contribution of genetic variations in the opioidergic system, which is linked to the processing of both, reward and pain, to this prediction. We used the monetary incentive delay task to assess reward processing, the Children's Somatization Inventory as measure of pain complaints and tested the effects of 2 single nucleotide polymorphisms (rs1799971/rs563649) of the human μ-opioid receptor gene. We found a significant prediction of pain complaints by responses in the dorsal striatum during reward feedback, independent of genetic predisposition. The relationship of pain complaints and activation in the periaqueductal gray and ventral striatum depended on the T-allele of rs563649. Carriers of this allele also showed more pain complaints than CC-allele carriers. Therefore, brain responses to reward outcomes and higher sensitivity to pain might be related already early in life and may thus set the course for pain complaints later in life, partly depending on a specific opioidergic genetic predisposition.

Brain responses to reward and pain sensitivity might be related early in life and set the course for later pain complaints, associated with opioidergic genes.

Departments of aCognitive and Clinical Neuroscience and

bChild and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

cDepartment of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria

dDiscipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College Dublin, Dublin, Ireland

eUniversity Medical Centre Hamburg-Eppendorf, Institute of Systems Neuroscience, Hamburg, Germany

fDepartment of Psychiatry, Université de Montréal, CHU Ste Justine Hospital, Montréal, QC, Canada

gDepartment of Psychological Medicine and Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom

hMedical Research Council—Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom

iNeurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France

jDepartment of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany

kDepartments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA

lPhysikalisch-Technische Bundesanstalt, Berlin, Germany

mInstitut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 “Neuroimaging & Psychiatry,” University Paris Sud, University Paris Descartes—Sorbonne Paris Cité; and Maison de Solenn, Paris, France

nRotman Research Institute, Baycrest and Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada

oDepartment of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany

pDepartment of Psychology, University College Dublin, Dublin, Ireland

Corresponding author. Address: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, J 5, D-68159 Mannheim, Germany. Tel.: +49-621-1703 6306; fax: +49-621-1703 6305. E-mail address: frauke.nees@zi-mannheim.de (F. Nees).

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

Received May 02, 2016

Received in revised form August 10, 2016

Accepted August 26, 2016

© 2017 International Association for the Study of Pain
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