Serotonergic gene-to-gene interaction is associated with mood and GABA concentrations but not with pain-related cerebral processing in fibromyalgia subjects and healthy controls

Ellerbrock, Isabel; Sandström, Angelica; Tour, Jeanette; Fanton, Silvia; Kadetoff, Diana; Schalling, Martin; Jensen, Karin B.; Sitnikov, Rouslan

doi:10.1186/s13041-021-00789-4

Cited by 13 publications

(3 citation statements)

References 89 publications

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“…There was a significant effect of 5-HTT and an interaction between 5-HTT x 5-HT1a regarding HAD-D, i.e. assessment of depression, data reported elsewhere [47]. Also, a significant gene-to-gene interaction with HAD-D was found regarding 5-HTT x 5-HT1a x OPRM1 (F = 6.07, df = 1, p = 0.016).…”

Section: Associations Between Genetic Polymorphisms and Fm Symptomssupporting

confidence: 68%

The OPRM1 gene and interactions with the 5-HT1a gene regulate conditioned pain modulation in fibromyalgia patients and healthy controls

et al. 2022

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Fibromyalgia (FM) patients have dysfunctional endogenous pain modulation, where opioid and serotonergic signaling is implicated. The aim of this study was to investigate whether genetic variants in the genes coding for major structures in the opioid and serotonergic systems can affect pain modulation in FM patients and healthy controls (HC). Conditioned pain modulation (CPM), evaluating the effects of ischemic pain on pressure pain sensitivity, was performed in 82 FM patients and 43 HC. All subjects were genotyped for relevant functional polymorphisms in the genes coding for the μ-opioid receptor (OPRM1, rs1799971), the serotonin transporter (5-HTT, 5-HTTLPR/rs25531) and the serotonin 1a receptor (5-HT1a, rs6295). Results showed the OPRM1 G-allele was associated with decreased CPM. A significant gene-to-gene interaction was found between the OPRM1 and the 5-HT1a gene. Reduced CPM scores were seen particularly in individuals with the OPRM1 G*/5-HT1a CC genotype, indicating that the 5-HT1a CC genotype seems to have an inhibiting effect on CPM if an individual has the OPRM1 G-genotype. Thus, regardless of pain phenotype, the OPRM1 G-allele independently as well as with an interaction with the 5-HT1a gene influenced pain modulation. FM patients had lower CPM than HC but no group differences were found regarding the genetic effects on CPM, indicating that the results reflect more general mechanisms influencing pain modulatory processes rather than underlying the dysfunction of CPM in FM. In conclusion, a genetic variant known to alter the expression of, and binding to, the my-opioid receptor reduced a subject’s ability to activate descending pain inhibition. Also, the results suggest a genetically inferred gene-to-gene interaction between the main opioid receptor and a serotonergic structure essential for 5-HT transmission to modulate pain inhibition. The results in this study highlight the importance of studying joint synergistic and antagonistic effects of neurotransmittor systems in regard to pain modulation.

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Section: Associations Between Genetic Polymorphisms and Fm Symptomssupporting

confidence: 68%

The OPRM1 gene and interactions with the 5-HT1a gene regulate conditioned pain modulation in fibromyalgia patients and healthy controls

et al. 2022

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“…FM female individuals carrying the 5-HTR2A polymorphism of Cytosine-Thymine (CT) genotype have lower pain thresholds than those with TT and CC genotypes [ 41 ]. FM individuals with a combined 5-HT1a CC and 5-HTT -high expression have the fewest depressive symptoms compared to individuals with a combined 5-HT1a CC/G and 5-HTT -low expression [ 53 ].…”

Section: Genetic Contributions To the Development Of Fmmentioning

confidence: 99%

A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia

et al. 2023

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This narrative review summarizes the current knowledge of the genetic and epigenetic contributions to the development of fibromyalgia (FM). Although there is no single gene that results in the development of FM, this study reveals that certain polymorphisms in genes involved in the catecholaminergic pathway, the serotonergic pathway, pain processing, oxidative stress, and inflammation may influence susceptibility to FM and the severity of its symptoms. Furthermore, epigenetic changes at the DNA level may lead to the development of FM. Likewise, microRNAs may impact the expression of certain proteins that lead to the worsening of FM-associated symptoms.

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“…So far, genetic studies that have examined the 5-HT 1A receptor and 5-HT 2A receptor gene polymorphisms, as well as studies measuring 5-HT blood levels, have produced mixed results [31][32][33]. In the case of the SERT, two genetic studies (one PET study and one study on gene expression) have also produced mixed results [34,35].…”

Section: Introductionmentioning

confidence: 99%

Serotonin Transporter mRNA Expression Is Reduced in the Peripheral Blood Mononuclear Cells of Subjects with Major Depression but Normal in Fibromyalgia

Villanueva-Charbonneau,

Potvin,

Marchand

et al. 2023

Brain Sciences

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Background: Fibromyalgia (FM) and major depression disorder (MDD) frequently co-occur. Both disorders may share common serotonergic alterations, although there is less evidence of such alterations in FM. It is also unclear as to whether these alterations are persistent over time or transient. The objectives of this study were to (i) examine the changes in mRNA expression of serotonin transporter (SERT) on the surface of peripheral blood mononuclear cells (PBMCs) in FM, MDD, and the FM + MDD subjects compared to healthy controls, and to (ii) evaluate the effect of drug treatment on SERT expression. Methods: PBMCs were isolated from FM, MDD, FM + MDD, and control subjects. SERT expression was analyzed at the mRNA level via quantitative real-time polymerase chain reaction. Statistical analyses were performed using analyses of variance and linear mixed-effects models. Results: SERT mRNA expression was significantly reduced in MDD subjects compared to controls (p < 0.001), but not in FM nor in FM + MDD subjects. Although the drug treatments improved symptoms in FM, MDD, and FM + MDD subjects, they had no significant effect on SERT mRNA expression. Conclusions: These results corroborate the role of the SERT in the pathophysiology of MDD, but not in FM, and show that the decreased mRNA expression of SERT is a persistent, rather than transient, phenomenon.

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Serotonergic gene-to-gene interaction is associated with mood and GABA concentrations but not with pain-related cerebral processing in fibromyalgia subjects and healthy controls

Cited by 13 publications

References 89 publications

The OPRM1 gene and interactions with the 5-HT1a gene regulate conditioned pain modulation in fibromyalgia patients and healthy controls

The OPRM1 gene and interactions with the 5-HT1a gene regulate conditioned pain modulation in fibromyalgia patients and healthy controls

A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia

Serotonin Transporter mRNA Expression Is Reduced in the Peripheral Blood Mononuclear Cells of Subjects with Major Depression but Normal in Fibromyalgia

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