SNPwatch: Genetic Variation In Morphine Receptor May Play A Part In Coping With Social Rejection

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

Two young girls bullying other young girl outdoors

It’s no accident that we often refer to rejection or insult as a slap in the face — research shows the same brain signaling pathways are involved in both physical and emotional pain.

And morphine, a drug well known for its ability to dull physical pain, also reduces separation-induced emotional distress in monkeys, dogs, guinea pigs, rats and chickens.  This is thought to depend on changes in signaling through a morphine receptor called MOR (mu-opioid receptor) that is also implicated in emotional pain in humans. Studies have shown that signaling through MOR is reduced when women recall upsetting events like the death of a loved one or the breakup of a romantic relationship.

Given that MOR seems to be at the center of the overlap between physical and emotional pain, researchers from the UCLA Department of Psychology wondered whether a genetic variation in the gene that encodes MOR that is already known to impact sensitivity to physical pain might also affect how thick-skinned a person is.

Baldwin M. Way and colleagues surveyed 122 healthy young adults about their sensitivity to social rejection.  The assessment measured the tendency of study subjects to be fearful that social interactions will result in hurt feelings, criticism and being a burden to others.  The results, published online this week in the Proceedings of the National Academy of Sciences, show that people with one or two Gs at SNP rs1799971 had significantly higher levels of self-reported sensitivity to social rejection than those with an A at both copies.

The G version of rs1799971 has previously been associated with needing more morphine for pain relief after surgery.

(23andMe customers can check their data for rs1799971 using the Browse Raw Data feature.)

A subset of the study participants also had their brains scanned in an fMRI machine while playing an online ball-tossing game.  The subjects thought they were playing with two people, but in reality they were interacting with a pre-set computer program.  The game simulated social rejection by having the subjects’ virtual playmates leave them out of the fun.

Just as in the survey, the G version of rs1799971 was associated with heightened responses to social rejection.  Higher brain activity was recorded in the anterior cingulate cortex and the anterior insula, brain regions associated with the processing of both physical and emotional pain, in people with one or two Gs.

As is usually the case, the results of this study should be considered preliminary until other researchers replicate them. But based on their results, along with previous research, the authors conclude that, “… at multiple biological levels, including the neurochemical, neuroanatomical, and now genetic, feeling hurt physically shares more than just linguistic commonality with feeling hurt socially.”


  • jloe

    Hello,

    Intriguingly there also seems to be a connection between this snp and pain sensitivity in conjunction with COMT genotype:
    PMID: 17156920
    See abstract
    “1: Pain. 2007 Jul;130(1-2):25-30. Epub 2006 Dec 6.
    Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene.
    Reyes-Gibby CC, Shete S, Rakvåg T, Bhat SV, Skorpen F, Bruera E, Kaasa S, Klepstad P.

    Department of Epidemiology, U.T.M.D. Anderson Cancer Center, Houston, TX, USA. creyes@mdanderson.org

    Pain is a complex human trait. It is likely that the interaction of multiple genes, each with a small individual effect, along with the effect of environmental factors, influences the clinical efficacy of opioids rather than a single gene alone. Polymorphisms in genes coding for the mu-opioid receptor (A118G) and catechol-O-methyl transferase (Val158Met) may be important modulators of opioid efficacy. We assessed joint effects of the OPRM1 and COMT genes in predicting morphine dose for cancer pain relief. We used genotype and clinical data from a pharmacokinetic study of morphine in 207 inpatients treated with stable morphine dose for at least 3 days by Palliative Medicine Specialists. Results showed significant variation in morphine dose requirement by genotype groups: carriers of COMT Val/Val and Val/Met genotype required 63% and 23%, respectively, higher morphine dose compared to carriers of Met/Met genotype (p=0.02). Carriers of OPRM1 GG genotype required 93% higher morphine dose compared to carriers of AA genotypes (p=0.012). When we explored for joint effects, we found that carriers of the OPRM1 AA and COMT Met/Met genotype required the lowest morphine dose to achieve pain relief (87 mg/24 h; 95%CI=57,116) and those with neither Met/Met nor AA genotype needed the highest morphine dose (147 mg/24 h; 95%CI=100,180). The significant joint effects for the Met/Met and AA genotypes (p<0.012) persisted, even after controlling for demographic and clinical variables in the multivariable analyses. Future studies are needed to further characterize the joint effects of multiple genes, along with demographic and clinical variables, in predicting opioid dose."

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