Fear of pain moderates the relationship between self-reported fatigue and methionine allele of catechol-O-methyltransferase gene in patients with fibromyalgia

Ferrera, David; Mercado, Francisco; Peláez, Irene; Martínez‐Íñigo, David; Fernandes-Magalhaes, Roberto; Barjola, Paloma; Écija, Carmen; Dı́az-Gil, Gema; Gómez-Esquer, Francisco

doi:10.1371/journal.pone.0250547

Cited by 10 publications

(11 citation statements)

References 68 publications

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“…Beyond widespread pain, patients commonly have additional physical, affective and cognitive alterations (Aparicio et al, 2013;Bell et al, 2018;Ferrera et al, 2021;Mercado et al, 2022). Indeed, current evidence has confirmed the principal role of attentional and affective processes in influencing pain hypersensitivity in fibromyalgia (Peters et al, 2000;Gracely et al, 2002;Geisser et al, 2003;Giesecke et al, 2005;Bartley et al, 2009;Duschek et al, 2014;Ellingson et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological indices of pain expectation abnormalities in fibromyalgia patients

Barjola

Peláez²,

Ferrera³

et al. 2022

Front. Hum. Neurosci.

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Fibromyalgia is a chronic pain syndrome characterized by dysfunctional processing of nociceptive stimulation. Neuroimaging studies have pointed out that pain-related network functioning seems to be altered in these patients. It is thought that this clinical symptomatology may be maintained or even strengthened because of an enhanced expectancy for painful stimuli or its forthcoming appearance. However, neural electrophysiological correlates associated with such attentional mechanisms have been scarcely explored. In the current study, expectancy processes of upcoming laser stimulation (painful and non-painful) and its further processing were explored by event-related potentials (ERPs). Nineteen fibromyalgia patients and twenty healthy control volunteers took part in the experiment. Behavioral measures (reaction times and subjective pain perception) were also collected. We manipulated the pain/no pain expectancy through an S1–S2 paradigm (cue-target). S1 (image: triangle or square) predicted the S2 appearance (laser stimulation: warmth or pinprick sensation). Laser stimuli were delivered using a CO2 laser device. Temporal and spatial principal component analyses were employed to define and quantify the ERP component reliability. Statistical analyses revealed the existence of an abnormal pattern of pain expectancy in patients with fibromyalgia. Specifically, our results showed attenuated amplitudes at posterior lCNV component in anticipation of painful stimulation that was not found in healthy participants. In contrast, although larger P2 amplitudes to painful compared to innocuous events were shown, patients did not show any amplitude change in this laser-evoked response as a function of pain predictive cues (as occurred in the healthy control group). Additionally, analyses of the subjective perception of pain and reaction time indicated that laser stimuli preceded by pain cues were rated as more painful than those signaling non-pain expectancy and were associated with faster responses. Differences between groups were not found. The present findings suggest the presence of dysfunction in pain expectation mechanisms in fibromyalgia that eventually may make it difficult for patients to correctly interpret signs that prevent pain symptoms. Furthermore, the abnormal pattern in pain expectancy displayed by fibromyalgia patients could result in ineffective pain coping strategies. Understanding the neural correlates of pain processing and its modulatory factors is crucial to identify treatments for chronic pain syndromes.

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Section: Introductionmentioning

confidence: 99%

Electrophysiological indices of pain expectation abnormalities in fibromyalgia patients

Barjola

Peláez²,

Ferrera³

et al. 2022

Front. Hum. Neurosci.

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“…Catechol-O-methyltransferase (COMT) gene is one of the possible candidates associated, at least partially, with interindividual variability in physical, psychological or cognitive symptoms in fibromyalgia [3,[19][20][21][22][23][24]. This gene encodes an enzyme of the same name, which is involved in the degradation of catecholamines, such as dopamine, adrenaline or noradrenaline [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

“…The Met/Met genotype is associated with three to four times lower activity of the COMT enzyme than Val/Val genotype [32], whereas Met/Val seems to have intermediate levels of enzyme activity [33]. Briefly, the Met/ Met genotype of the Val158Met polymorphism has been associated with an increase in tender points [19][20][21][22], the severity of fatigue [3], and depression or anxiety symptomatology in fibromyalgia [23,34]. Complementarily, recent findings regarding cognitive impairment have indicated that patients with fibromyalgia bearing the Val/Val genotype showed a worsening in working memory tasks compared to healthy control participants carrying the same genotype [24].…”

Section: Introductionmentioning

confidence: 99%

Working memory dysfunction in fibromyalgia is associated with genotypes of the catechol- O-methyltransferase gene: an event-related potential study

Ferrera

Gómez-Esquer

Peláez

et al. 2022

Eur Arch Psychiatry Clin Neurosci

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Recent findings have associated different COMT genotypes with working memory capacity in patients with fibromyalgia. Although it is thought that the COMT gene may influence neural correlates (P2 and P3 ERP components) underlying working memory impairment in this chronic-pain syndrome, it has not yet been explored. Therefore, the aim of the present research was to investigate the potential effect of the COMT gene in fibromyalgia patients on ERP working memory indices (P2 and P3 components). For this purpose, 102 participants (51 patients and 51 healthy control participants) took part in the experiment. Event-related potentials and behavioral responses were recorded while participants performed a spatial n-back task. Participants had to decide if the stimulus coincided or not in the same location as the one presented one (1-back condition) or two (2-back condition) trials before. Genotypes of the COMT gene were determined through a saliva sample from all participants. Present results significantly showed lower working memory performance (p < 0.05) in patients with fibromyalgia as compared to control participants (higher rate of errors and slower reaction times). At neural level, we found that patients exhibited enhanced frontocentral and parieto-occipital P2 amplitudes compared to control participants (p < 0.05). Interestingly, we also observed that only fibromyalgia patients carrying the Val/Val genotype of the COMT gene showed higher frontocentral P2 amplitudes than control participants (p < 0.05). Current results (behavioral outcomes and P2 amplitudes) confirmed the presence of an alteration in working memory functioning in fibromyalgia. The enhancement of frontocentral P2 could be reflecting that these patients would manifest an inefficient way of activating executive attention processes, in carriers of the Val/Val genotype of COMT. To our knowledge, the present findings are the first linking neural indices of working memory dysfunctions and COMT genotypes in fibromyalgia. Applying a subgroup of patient’s strategy based on this genetic marker could be useful to establish more tailored therapeutical approaches.

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“…By regulating the dopaminergic pathways, COMT participates in the opioidergic central processing of pain [ 3 ]. A relationship between methionine alleles of the COMT gene and fatigue has even been suggested, which could be moderated by different levels of fear of pain, establishing an association between psychological and physical factors [ 4 ]. Among Spanish women with FM, an early study found an association between rs4818 polymorphism and self-reported pain [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: the al-Ándalus project

et al. 2021

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Objectives It is widely acknowledged that the experience of pain is promoted by both genetic susceptibility and environmental factors such as engaging in physical activity (PA) and that pain-related cognitions are also important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate-genes) and the gene-gene, gene-PA, and gene-sedentary behaviour interactions with pain and pain-related cognitions in women with fibromyalgia. Methods Saliva samples from 274 women with fibromyalgia (aged 51.7 ± 7.7 years) were collected for extracting DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis was also performed. Results The rs6311 and rs6313 polymorphisms (HTR2A) were individually related to algometer scores. The interaction of rs4818 (COMT) and rs1799971 (OPRM1) was related to pain catastrophizing. Five gene-behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914 (ADR1A), rs6860 (CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the SF-36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and severity of fibromyalgia symptoms (codominant model, p-value: 0.032). Conclusion The HTR2A gene (individually), COMT and OPRM1 gene-gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT, and SCN9A genes were associated with pain-related outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene-sedentary behaviour interaction to pain and pain catastrophizing in women with fibromyalgia. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.

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Fear of pain moderates the relationship between self-reported fatigue and methionine allele of catechol-O-methyltransferase gene in patients with fibromyalgia

Cited by 10 publications

References 68 publications

Electrophysiological indices of pain expectation abnormalities in fibromyalgia patients

Electrophysiological indices of pain expectation abnormalities in fibromyalgia patients

Working memory dysfunction in fibromyalgia is associated with genotypes of the catechol- O-methyltransferase gene: an event-related potential study

Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: the al-Ándalus project

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