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Polymorphism in the µ-opioid receptor gene (OPRM1) modulates neural processing of physical pain, social rejection and error processing

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Abstract

Variations of the µ-opioid receptor gene OPRM1 have been shown to modulate pain perception with some evidence pointing towards a modulation of not only physical but also “psychological pain”. In line with suggestions of a common neural network involved in the processing of physical pain and negative and distressing stimuli, like social rejection as a psychologically harmful event, we examined the influence of the A118G polymorphism on the neural processing of physical and non-physical pain. Using fMRI, we investigated a sample of 23 females with the more frequent AA genotype, and eight females with the relatively rare but more pain-sensitive AG genotype during electrical stimulation to the dorsum of the non-dominant hand. Non-physical pain was investigated using Cyberball, a virtual ball-tossing game, to induce experiences of non-self-dependent social rejection. A Go/NoGo task with an increased risk of self-dependent erroneous performance was used as a control task to investigate the effects of negative feedback as a more cognitive form of distress. Relative to A118G homozygous A-allele carriers, G-allele carriers showed significantly increased activation of the supplementary motor area/superior frontal gyrus and the precentral gyrus during electrical stimulation. Increased activation of the secondary sensorimotor cortex (SII) was found during social exclusion and during negative feedback. We demonstrate that brain regions particularly related to the somatosensory component of pain processing are modulated by variations in OPRM1. Influences were evident for both physical and psychological pain processing supporting the assumption of shared neural pathways.

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Acknowledgments

Special thanks to Ursula Botzenhardt and Sabrina Skambraks for excellent technical assistance and to Prof. Dr. L. Bullinger for his laboratory support. In addition, many thanks to the team of BioGlobe Molecular Genetic Laboratory, particularly Dr. N. Storm, for excellent consulting and advanced service in genotyping. The study was conducted within the framework of a fellowship for individual doctoral training funded through the Landesgraduiertenförderung (LGFG).

Conflict of interest

The authors MB, RCG, GG and BA declare that they have no conflicts of interest. PLP declares no competing interests. He is PI in a study for Lundbeck. He got research grants from the BMBF (German Ministries for Research and Education) and the BfArM (German Federal Institute for Drugs and Medical devices). He received travel grants from the DFG, DAAD and IACAPAP. He is not a stockholder or share-holder in the pharmaceutical industry.

Ethical standard

All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry and Psychotherapy, Ulm University, Ulm, Germany

    M. Bonenberger, P. L. Plener & R. C. Groschwitz

  2. Department of Psychiatry and Psychotherapy, Ulm University, Ulm, Germany

    G. Grön & B. Abler

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  1. M. Bonenberger
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  2. P. L. Plener
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  3. R. C. Groschwitz
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Correspondence to M. Bonenberger.

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Bonenberger, M., Plener, P.L., Groschwitz, R.C. et al. Polymorphism in the µ-opioid receptor gene (OPRM1) modulates neural processing of physical pain, social rejection and error processing. Exp Brain Res 233, 2517–2526 (2015). https://doi.org/10.1007/s00221-015-4322-9

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