Influence of catechol-O-methyltransferase (COMT) gene polymorphisms in pain sensibility of Brazilian fibromialgia patients

Barbosa, Flávia Regina; Matsuda, Josie Budag; Mazucato, Mendelson; França, Suzelei de Castro; Zingaretti, Sônia Marli; Silva, Lucienir Maria da; Martinez-Rossi, Nilce M.; Júnior, Milton Faria; Marins, Mozart; Fachin, Ana Lúcia

doi:10.1007/s00296-010-1659-z

Cited by 69 publications

(63 citation statements)

References 26 publications

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“…In contrast to our results, some studies have found that women with FMS with the Met/Met genotype exhibited higher levels of disability (higher score in the Fibromyalgia Impact Questionnaire [FIQ]) than those with the Val/Val and Val/Met genotypes (Barbosa et al, 2012;Fernández-de-Las-Peñas et al, 2012;Josep García-Fructuoso et al, 2006).…”

Section: Discussioncontrasting

confidence: 85%

“…According to their results the OR for the Met allele being a risk allele for FMS was 1.28, 95% CI 1.06-1.55, p ¼ 0.01. One study was excluded because of the lack of HWE in the control group in this meta-analysis (Barbosa et al, 2012). They examined the role of ethnicity in heterogeneity by dividing the studies into three groups: Non-Hispanic Caucasians, Hispanic Caucasians, and Middle East populations.…”

Section: Discussionmentioning

confidence: 99%

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Clinical symptoms in fibromyalgia are associated to catechol-O-methyltransferase (COMT) gene Val158Met polymorphism

Inanir

Karakuş²,

Ateş³

et al. 2014

Xenobiotica

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1. Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. The aim of this study was to explore the frequency and clinical significance of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism in a large cohort of Turkish patients with FMS. 2. The study included 379 FMS patients and 290 controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses. 3. The genotype frequencies of Val158Met polymorphism showed a small difference between FMS patients and healthy controls (p = 0.047), however, the Met/Met genotype was significantly higher in FMS patients than healthy controls (p = 0.016). No difference was observed for allele frequencies between two groups. Stratification analysis according to clinical features for this disease reveals that weight, FMS Impact Questionnaire score, algometry and Raynaud's syndrome, were detected to have statistically significant associations with Val158Met polymorphism (p = 0.037, p = 0.042, p = 0.039 and p = 0.033, respectively). Pain sensitivity, measured by algometry, was statistically higher in patients with Met/Met genotype than the patients with Val/Val and Val/Met genotypes (p = 0.017). 4. The results of this study suggested that COMT gene Val158Met polymorphism is positively associated with FMS and play a relevant role in the clinical symptoms of the disease.

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Section: Discussioncontrasting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Clinical symptoms in fibromyalgia are associated to catechol-O-methyltransferase (COMT) gene Val158Met polymorphism

Inanir

Karakuş²,

Ateş³

et al. 2014

Xenobiotica

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“…The OR for the Met allele being a risk allele for fibromyalgia or widespread pain was 1.28, 95% CI 1.06-1.55, P = 0.01, n = 3811. One study [47] was excluded because of the lack of HWE in the control group.…”

Section: Fibromyalgia or Chronic Widespread Pain And Rs4680mentioning

confidence: 99%

Catechol-O-methyltransferase gene polymorphism and chronic human pain

Tammimäki

Männistö

2012

Pharmacogenetics and Genomics

147

109

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In human studies, low COMT (catechol-O-methyltransferase) activity has been associated with increased sensitivity to acute clinical preoperative or postoperative pain. We explored the association between the COMT genotype and three chronic pain conditions: migrainous headache, fibromyalgia, or chronic widespread pain and chronic musculoskeletal pain. Furthermore, we evaluated whether COMT genotype affects the efficacy of opioids in chronic pain. After a systematic literature review, we carried out meta-analyses on the three chronic pain conditions. The efficacy of opioids was evaluated using a systematic review only. The meta-analyses showed that fibromyalgia or chronic widespread pain is the only type of chronic pain that could be associated with the COMT single nucleotide polymorphism rs4680 (Val158Met). Met158, which results in the low-activity variant of COMT, is the risk allele. In chronic clinical pain, the effect of the COMT polymorphism depends on the pain condition. Low COMT activity is not associated with migrainous headache or chronic musculoskeletal pain conditions, but it may increase the risk for fibromyalgia or chronic widespread pain. Low COMT activity increases opioid receptors and enhances opioid analgesia and adverse effects in some cancer pains. Findings from animal studies that have utilized COMT inhibitors elucidate the mechanism behind these findings. In rodent pain models, COMT inhibitors are pronociceptive, except for neuropathic pain models, where nitecapone was found to be antiallodynic. The complex interplay between enhanced adrenergic and dopaminergic activity in different parts of the nociceptive system probably explains the complicated actions of low COMT activity.

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“…Patients exhibit increased levels of catecholamines 9-11 alongside diminished activity of catechol-O-methyltransferase (COMT), 12,13 a ubiquitously expressed enzyme that metabolizes catecholamines to their inactive derivatives. 14 Furthermore, functional variants in the COMT gene that reduce COMT activity 13,15,16 are associated with increased susceptibility to FM, 17-21 TMD 22 and experimental pain 22,23 as well as impaired response to treatment. 24,25 It is estimated, based on the frequency of allele variation, that nearly two-thirds of patients with chronic pain disorders possess the low-activity COMT variants.…”

Section: Introductionmentioning

confidence: 99%

Persistent Catechol-O-methyltransferase–dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors

2016

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Background Patients with chronic pain disorders exhibit increased levels of catecholamines alongside diminished activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. The authors found that acute pharmacologic inhibition of COMT in rodents produces hypersensitivity to mechanical and thermal stimuli via β-adrenergic receptor (βAR) activation. The contribution of distinct βAR populations to the development of persistent pain linked to abnormalities in catecholamine signaling requires further investigation. Methods Here, the authors sought to determine the contribution of peripheral, spinal, and supraspinal βARs to persistent COMT-dependent pain. They implanted osmotic pumps to deliver the COMT inhibitor OR486 (Tocris, USA) for 2 weeks. Behavioral responses to mechanical and thermal stimuli were evaluated before and every other day after pump implantation. The site of action was evaluated in adrenalectomized rats receiving sustained OR486 or in intact rats receiving sustained βAR antagonists peripherally, spinally, or supraspinally alongside OR486. Results The authors found that male (N = 6) and female (N = 6) rats receiving sustained OR486 exhibited decreased paw withdrawal thresholds (control 5.74 ± 0.24 vs. OR486 1.54 ± 0.08, mean ± SEM) and increased paw withdrawal frequency to mechanical stimuli (control 4.80 ± 0.22 vs. OR486 8.10 ± 0.13) and decreased paw withdrawal latency to thermal heat (control 9.69 ± 0.23 vs. OR486 5.91 ± 0.11). In contrast, adrenalectomized rats (N = 12) failed to develop OR486-induced hypersensitivity. Furthermore, peripheral (N = 9), but not spinal (N = 4) or supraspinal (N = 4), administration of the nonselective βAR antagonist propranolol, the β2AR antagonist ICI-118,511, or the β3AR antagonist SR59230A blocked the development of OR486-induced hypersensitivity. Conclusions Peripheral adrenergic input is necessary for the development of persistent COMT-dependent pain, and peripherally-acting βAR antagonists may benefit chronic pain patients.

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Influence of catechol-O-methyltransferase (COMT) gene polymorphisms in pain sensibility of Brazilian fibromialgia patients

Cited by 69 publications

References 26 publications

Clinical symptoms in fibromyalgia are associated to catechol-O-methyltransferase (COMT) gene Val158Met polymorphism

Clinical symptoms in fibromyalgia are associated to catechol-O-methyltransferase (COMT) gene Val158Met polymorphism

Catechol-O-methyltransferase gene polymorphism and chronic human pain

Persistent Catechol-O-methyltransferase–dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors

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