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COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia.

ABSTRACT: Forty-five women with fibromyalgia (FM) engaged in a 30-day electronic diary assessment, recording daily ratings of pain and 2 forms of maladaptive coping: pain catastrophizing and pain attention. Participants were genotyped for the val(158)met single nucleotide polymorphism (rs4680) in the catechol-O-methyltransferase (COMT) gene. COMT genotype moderated the daily relations of both maladaptive coping processes and pain. FM women with the homozygous met/met genotype evidenced more pain on days when pain catastrophizing was elevated relative to heterozygous and homozygous val(158) carriers. FM women with the homozygous met/met genotype evidenced more pain on days when pain attention was elevated relative to those with the homozygous val/val genotype. Evidence is presented to suggest that these are independent effects. The findings provide multimeasure and multimethod support for genetic moderation of a maladaptive coping and pain process, which has been previously characterized in a sample of postoperative shoulder pain patients. Further, the findings advance our understanding of the role of COMT in FM, suggesting that genetic variation in the val(158)met polymorphism may affect FM pain through pathways of pain-related cognition. This study examined 2 forms of maladaptive coping: pain catastrophizing and pain attention. The findings provide multimeasure and multimethod support for genetic moderation of a maladaptive coping and pain process and suggest that genetic variation in the val(158)met polymorphism may affect fibromyalgia pain through pathways of pain-related cognition.

SUBMITTER: Finan PH

PROVIDER: S-EPMC3053137 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia.

Finan Patrick H PH Zautra Alex J AJ Davis Mary C MC Lemery-Chalfant Kathryn K Covault Jonathan J Tennen Howard H

Pain 20101203 2

Forty-five women with fibromyalgia (FM) engaged in a 30-day electronic diary assessment, recording daily ratings of pain and 2 forms of maladaptive coping: pain catastrophizing and pain attention. Participants were genotyped for the val(158)met single nucleotide polymorphism (rs4680) in the catechol-O-methyltransferase (COMT) gene. COMT genotype moderated the daily relations of both maladaptive coping processes and pain. FM women with the homozygous met/met genotype evidenced more pain on days w ...[more]

PMID: 21130573

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Project description:BACKGROUND:Osteoarthritis (OA) of the knee is a common and increasingly prevalent condition that is one of the primary causes of chronic pain. Staying physically active protects against disability from knee OA but is also very challenging. A critical but unexamined question is whether patients at greatest risk for becoming less active are those with a genetic predisposition for greater sensitivity to daily pain. AIMS:We examined day-to-day variability in knee OA pain for patients with different variants of catechol-O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) single nucleotide polymorphisms (SNPs), and whether patients with a specific genotype experience more pain following daily physical activity. We predicted that patients having one or more copies of the Met158 allele of COMT rs4680 (A-A or A-G) and one or more copies of the Asp40 allele of OPRM1 rs1799971 (A-G or G-G) would show greater pain variability. We expected to see the same pattern for these SNPs with regard to moderation (i.e., exacerbation) of the activity-pain association. METHODS:A total of 120 knee OA patients reported on their pain 3 times per day over 22 days using handheld computers, and wore an accelerometer to capture daily physical activity. Multilevel modeling was used to examine the magnitude of within-person variability in pain by genetic group. We also examined whether lagged, within-patient associations between level of activity in the afternoon (i.e., minutes of moderate intensity activity, and number of steps) and knee pain at the end-of-day were moderated by between-patient differences in genotype. RESULTS:Regarding OPRM1 rs1799971 (Asn40Asp), patients with two copies of the Asn40 allele showed the greatest day-to-day pain variability. Regarding COMT rs4680 (Val158Met), patients with the Val/Val genotype showed the greatest pain variability and also experienced the greatest increase in pain as a result of physical activity. A similar pattern of findings across bi-directional temporal lags was consistent with a negative feedback loop between daily physical activity and pain according to genotype. Consistent with some previous studies, there were no significant between-person differences in daily pain when comparing patients according to COMT rs4680, or OPRM1 rs1799971. CONCLUSION:This study provides preliminary evidence that patients with certain genotypes for COMT rs4680 and OPRM1 rs1799971 (G-G and A-A, respectively) experience more variability in their day-to-day pain and exacerbation of pain after daily physical activity compared to patients with other genotypes. Our findings should be replicated in larger study populations. IMPLICATIONS:Previous clinical research has focused primarily on differences in average level of pain between patients with and without a specific genotype. Assessment of within-person variability through repeated measurements in daily life enhances the reliability, power, and ecological validity of phenotypic measurement.

Project description:BackgroundClinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately.MethodsWe performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group (pregabalin 150-600 mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100 mm visual analogue pain scale [VAS]).ResultsComparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p < 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p < 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p < 0.0001) for those experiencing >/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p < 0.0001) for those achieving a low level of pain at trial end (<30 mm on the VAS). Patients achieving both >/= 50% pain improvement and a pain score <30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p < 0.0001). Analysing answers to the other questions yielded qualitatively similar results.ConclusionsEffective pain treatment goes along with benefit regarding work. A reduction in time off work >1 day per week can be achieved in patients with good pain responses.

Project description:ObjectiveSeveral epidemiological and clinical reports associate fibromyalgia (FM) with seizure disorders, and clinical studies associate FM diagnosis with psychogenic non-epileptic seizures. However, these associations rely on self-reports of being diagnosed with FM or unstandardized clinical diagnosis in combination with small samples. We investigated the association of FM and self-reported seizures using a large rheumatic disease databank and the current established self-reported, symptom-based FM diagnostic criteria.MethodsWe selected a random observation from 11,378 subjects with rheumatoid arthritis (RA), 2,390 (21.0%) of whom satisfied 2016 revised criteria for FM. Patients were inquired about the presence of any kind of seizures in the previous 6 months, anti-epileptic medications, and patient-reported symptoms and outcomes.ResultsSeizures were reported by 89 RA patients who met FM criteria (FM+) and by 97 patients who did not (FM-), resulting in an age- and sex-adjusted seizure prevalence of 3.74 (95% CI 2.95 to 4.53) per 100 FM+ subjects and 1.08 (95% CI 0.87 to 1.30) in FM- subjects. The seizure odds ratio of FM+ to FM- cases was 3.54 (95% CI 2.65 to 4.74). Seizures were associated to a very similar degree with symptom reporting (somatic symptom count and comorbidity index) as to FM diagnosis variables. RA patients reporting seizures also reported worse pain, quality of life, and functional status. Seizure patients treated with anti-seizure medication had worse outcomes and more comorbidities than seizure patients with no seizure drugs.ConclusionsWe found a significant and similar association of both FM diagnostic variables and FM-related symptom variables, including the number of symptoms and comorbidities, with self-reported seizures in people with RA. The observed association was similar to those found in previous studies of symptoms variables and seizures and does not suggest a unique role for fibromyalgia diagnosis. Rather, it suggests that multi-symptom comorbidity is linked to seizures in a complex and not yet clearly understood way. As the current study relied on self-reported seizures and was not able to distinguish between epileptic and psychogenic nonepileptic seizures, future studies are needed to replicate the findings using both validated FM criteria assessments and clinically verified diagnoses of epileptic and psychogenic seizures.

Project description:Previous research has shown a consistent association among genetic factors, psychological symptoms and pain associated with fibromyalgia. However, how these symptoms interact to moderate genetic factors in fibromyalgia has rarely been studied to date. The present research investigates whether psychological symptoms can moderate the effects of catechol-O-methyltransferase on pain and fatigue. A total of 108 women diagnosed with fibromyalgia and 77 healthy control participants took part in the study. Pain, fatigue, and psychological symptoms (anxiety, depression, pain catastrophizing, fear of pain and fear of movement) were measured by self-report questionnaires. Two types of statistical analyses were performed; the first was undertaken to explore the influences of COMT genotypes on clinical symptoms by comparing patients with fibromyalgia and healthy controls. In the second analysis, moderation analyses to explore the role of psychological symptoms as potential factors that moderate the relationship between pain/fatigue and COMT genotypes were performed. The main results indicated that patients carrying the Met/Met genotype reported significantly higher levels of fatigue than heterozygote carriers (i.e., Met/Val genotype) and higher levels of fatigue, but not significantly different, than Val homozygote carriers. Among patients with fibromyalgia carrying methionine alleles (i.e., Met/Met + Met/Val carriers), only those who scored high on medical fear of pain, experienced an intensified feeling of fatigue. Thus, the present research suggests that fear of pain, as a psychological symptom frequently described in fibromyalgia may act as a moderating factor in the relationship between the Met allele of the COMT gene and the increase or decrease in self-reported fatigue. Although further research with wider patient samples is needed to confirm the present findings, these results point out that the use of psychological interventions focused on affective symptomatology might be a useful tool to reduce the severity of fibromyalgia.

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COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia.

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COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia.

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