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Genetics and Labor Pain Behavior
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Inger Sundström Poromaa)
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Labor may perhaps be the most painful a woman might experience, although characterized by large inter-individual variability. The perceived pain during labor is the result of diverse factors, i.e. her previous pain experiences, the analgesia she receives and maybe also her genes. The overall aim of this thesis was to investigate biological and psychological mechanisms underlying inter-individual differences in labor pain related behaviors.

The mechanisms that characterize endogenous pain relief during labor are not fully understood, though it is known to be partly explained by the effects of β-endorphin (BE). BE plasma levels were followed longitudinally in a cohort of pregnant women and were found to remain unchanged between early and late pregnancy, although with a nadir in the beginning of the third trimester. Furthermore, women with low levels of BE in plasma at the end of the third trimester, required second line labor analgesia to a significantly higher extent than women with normal levels.

In a population-based sample of 814 pregnant women we investigated if inter-individual differences in labor pain related behavior was influenced by the pain-protective single nucleotide polymorphism (SNP) combination of guanosine triphosphate cyclohydrolase (GCH1) and the opioid receptor µ-1 gene (OPRM1) A118G SNP. We identified a possible association between the pain-protective SNP combination of GCH1 and use of second line analgesia. No association was found between the OPRM1 and use of analgesia or labor pain related behavior.

The association between self-rated antenatal depressed mood and anxiety in relation to pain behaviors and self-reported pain during labor was investigated. We found that depressed mood during pregnancy is associated with early arrival to the delivery department, whereas antenatal anxiety is associated with increased self-rated pain prior to labor analgesia. 

In conclusion, although an increasing number of studies strongly suggest that genetic predisposition plays an important role in pain and pain-related mechanisms, GCH1 and OPRM1 has little to offer in terms of individual counseling on labor analgesia. To enable the future use of genetic variability for pre-labor testing and counseling, a number of different genes reflecting pain mediation pathways, involving biological and psychological mechanisms, need to be analyzed in combination.      

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 60 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 729
Keyword [en]
anxiety, beta-endorphin, depressed mood, GCH1, labor analgesia, labor pain, OPRM1, SNP
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
URN: urn:nbn:se:uu:diva-162539ISBN: 978-91-554-8237-4 (print)OAI: oai:DiVA.org:uu-162539DiVA: diva2:461200
Public defence
2012-01-20, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-12-21 Created: 2011-12-01 Last updated: 2012-01-03Bibliographically approved
List of papers
1. Plasma Levels of beta-Endorphin During Pregnancy and Use of Labor Analgesia
Open this publication in new window or tab >>Plasma Levels of beta-Endorphin During Pregnancy and Use of Labor Analgesia
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2010 (English)In: Reproductive Sciences, ISSN 1933-7191, Vol. 17, no 8, 742-747 p.Article in journal (Refereed) Published
Abstract [en]

beta-endorphins are endogenous opioid substances produced by the pituitary gland and placenta. The aims of this project were to longitudinally follow plasma levels of beta-endorphin during pregnancy in women with a healthy pregnancy and to investigate whether plasma levels of beta-endorphin in late pregnancy are associated with need for additional pain medication beyond nitrous oxide during labor. Plasma samples from 45 women were collected at gestational weeks 10, 25, 28, 33 and 37, and beta-endorphin was analyzed by radioimmunoassay (RIA). Plasma levels of beta-endorphin displayed a significant decrease in gestational weeks 28 and 33 compared to week 10, followed by a subsequent increase between gestational weeks 28 and 37. However, there was no change in levels of beta-endorphin between gestational weeks 10 and 37. Low levels of beta-endorphin at the end of pregnancy were associated with need for additional pain medication beyond nitrous oxide during labor, although the causal relationship is unclear.

Keyword
Analgesia, beta-endorphin, labor, pain, pregnancy
National Category
Medical and Health Sciences Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-136009 (URN)10.1177/1933719110370059 (DOI)000279408100006 ()
Available from: 2010-12-10 Created: 2010-12-09 Last updated: 2012-01-03Bibliographically approved
2. Different SNP combinations in the GCH1 gene and use of labor analgesia
Open this publication in new window or tab >>Different SNP combinations in the GCH1 gene and use of labor analgesia
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2010 (English)In: Molecular pain, ISSN 1744-8069, Vol. 6, 41- p.Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this study was to investigate if there is an association between different SNP combinations in the guanosine triphosphate cyclohydrolase (GCH1) gene and a number of pain behavior related outcomes during labor. A population-based sample of pregnant women (n = 814) was recruited at gestational week 18. A plasma sample was collected from each subject. Genotyping was performed and three single nucleotide polymorphisms (SNP) previously defined as a pain-protective SNP combination of GCH1 were used. Results: Homozygous carriers of the pain-protective SNP combination of GCH1 arrived to the delivery ward with a more advanced stage of cervical dilation compared to heterozygous carriers and non-carriers. However, homozygous carriers more often used second line labor analgesia compared to the others. Conclusion: The pain-protective SNP combination of GCH1 may be of importance in the limited number of homozygous carriers during the initial dilation of cervix but upon arrival at the delivery unit these women are more inclined to use second line labor analgesia.

National Category
Medical and Health Sciences Pharmaceutical Sciences Biological Sciences
Identifiers
urn:nbn:se:uu:diva-134350 (URN)10.1186/1744-8069-6-41 (DOI)000282485300002 ()
Available from: 2010-11-25 Created: 2010-11-24 Last updated: 2016-11-16Bibliographically approved
3. The A118G Single Nucleotide Polymorphism of Human μ–Opioid Receptor Gene and Use of Labor Analgesia
Open this publication in new window or tab >>The A118G Single Nucleotide Polymorphism of Human μ–Opioid Receptor Gene and Use of Labor Analgesia
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2012 (English)In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 19, no 9, 962-967 p.Article in journal (Refereed) Published
Abstract [en]

The human µ-opioid receptor (MOR) is the major site of action of endogenous opioids and most of the clinically used opioid analgesics. The single-nucleotide polymorphism (SNP), A118G of the MOR 1 gene (OPRM1), has been associated with altered pain perception. The aim of this study was to investigate whether this polymorphism of OPRM1 is associated with a number of pain-related behaviors during labor. In this observational retrospective population-based study, pregnant women (n = 814) were recruited at gestational week 18. A plasma sample was collected from each participant and an SNP genotyping assay was performed. No differences in sociodemographic variables or labor pain-related outcomes, such as stage of cervical dilation on arrival at the delivery unit or use of any type of second-line analgesia during spontaneous labor, were found between noncarriers and G-allele carriers of OPRM1. We conclude that there is no association between the A118G polymorphism of OPRM1 regarding pain-related behavior during labor.

Keyword
analgesia, labor pain, OPRM1, single nucleotide polymorphism
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-162543 (URN)10.1177/1933719112438970 (DOI)000307540200007 ()
Projects
Genetics and Labor Pain Behavior
Available from: 2011-12-01 Created: 2011-12-01 Last updated: 2017-12-08Bibliographically approved
4. Anxiety, Depressed Mood and the Use of Labor Analgesia
Open this publication in new window or tab >>Anxiety, Depressed Mood and the Use of Labor Analgesia
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2016 (English)In: Archives of Women's Mental Health, ISSN 1434-1816, E-ISSN 1435-1102, Vol. 19, no 1, 11-16 p.Article in journal (Refereed) Published
Abstract [en]

Relatively little is known about mental health and labor pain. The aim of this study was to assess if self-rated antenatal depressed mood and anxiety are associated with pain-related behaviors and self-reported labor pain. We also wanted to replicate our previous finding of altered labor pain behavior in carriers of a specific guanosine triphosphate cyclohydrolase 1 gene (GCH1) haplotype. Ninety-nine women in gestational weeks 37 to 40 filled out questionnaires on depression and anxiety symptoms and later rated their labor pain by use of visual analog scales. Each subject was also genotyped for GCH1. Following adjustment for relevant confounders, women who arrived early to the delivery unit (cervical dilation < 5 cm) had a significantly higher antenatal Montgomery-sberg Depression Rating Scale (MADRS-S) score, p < 0.05, than late arrivers (cervical dilation > 5 cm). Women with increased Spielberger State-Trait Anxiety Inventory (STAI-T) scores reported higher self-rated pain prior to labor analgesia, p < 0.05, than women with low STAI-T scores. No association between the GCH1 pain-protective haplotype and cervical dilation was found, but a previously demonstrated association with increased use of second-line analgesia was confirmed. Depressed mood during pregnancy is associated with early arrival to the delivery department, whereas antenatal anxiety is associated with increased self-rated pain prior to labor analgesia.

Keyword
anxiety, depression, GCH1, labor pain
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-162544 (URN)10.1007/s00737-015-0572-6 (DOI)000369012400003 ()26392364 (PubMedID)
Projects
Genetics and Labor Pain Behavior
Available from: 2011-12-01 Created: 2011-12-01 Last updated: 2017-12-08Bibliographically approved

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