Jul 11, 2017

Advances in Research


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Based o previous findings of decreased concentrations of serotonin (5-HT) and norepinephrine (NE) metabolites in cerebrospinal fluid of patients with fibromyalgia (Russell et al. 1992) several studies have examined genetic polymorphism in serotonin, dopamine, and catecholamine systems in fibromyalgia. These studies have found significant association with fibromyalgia of promoter regions of the 5-HT transporter gene (5-HTT) (Ophenbacher et al, 1999) as well as 5-HT2A receptor gene located on the long arm of chromosome 13 (Boodny et al, 1999; Cohen et al, 2002). In addition several gen polymorphisms of serotonin receptor (HTR) subunit, including HTR3A and HTR3B, have been associated with fibromyalgia (Frank et al, 2004). Another polymorphism of considerable interest is related to the involvement of the COMT gene in patients with fibromyalgia. One study reported significant differences in allele frequencies of a COMT SNP (G1947A) among patients with fibromyalgia and controls (Gursoy et al, 2003). Also, a possible genetic association with fibromialgia has been detected for TACR1 gene, which encodes neurokinin 1 (NK1) receptor, the target for substance P (SP) (Abblin, 2005).

From: Pain Dynamics and Complexities, Daniel M. Doleys. Oxford University Press 2014.

EVIDENCE FOR A GENETIC PREDISPOSITION TO FIBROMYALGIA

From: New insights into the genetics of fibromyalgia
by Dong-Jin Park and Shin-Seok Lee

Genetic factors contributing to chronic pain

Pain commonly aggregates in families, and previous studies have shown that heritability explains up to 50% of the development of chronic pain [12]. Given such work [13], a revolution in molecular genetics followed, suggesting that some forms of chronic pain have genetic explanations.

The search for pain-related genes has primarily featured large linkage or association analyses; these showed that pain-related genes affected the expression or function of proteins in a manner influencing the pain response [12]. Currently, hundreds of pain-regulated genes that are thought to be relevant to pain perception or analgesia have been identified. These include the genes encoding voltage-gated sodium-channels (Nav), GTP cyclohydrolase 1 (GCH1), mu-opioid receptors, and catechol-O-methyl transferase (COMT); and various genes of the dopaminergic, glutamatergic, and GABAergic pathways [14]. Furthermore, numerous candidate genes have been identified from gene expression profiling (microarray) studies [15].

Familial aggregation of fibromyalgia

As the role played by genetic factors in pain mechanisms became clearer, much research effort focused on a possible genetic predisposition to FM. Familial aggregation among FM patients provided reasonable support for an association between genetic factors and the development of FM [16]. Pellegrino et al. [17] evaluated 17 families of FM patients to assess the evidence that FM might be an inherited condition. Although the study had a relatively small sample size, it was suggested that the mode of FM inheritance was autosomal-dominant. It was found that 26 (52%) of the enrolled parents and siblings exhibited clinical evidence of FM, and an additional 11 (22%), without apparent symptoms of FM, exhibited abnormal muscle consistency on palpation. Similar observations in terms of familial aggregation among FM patients were also reported in two studies by Buskila et al. [18] and Buskila and Neumann [19]. In one study, among 58 offspring of 20 complete nuclear families of FM-diagnosed mothers, 16 (28%) were found to have FM. As the exposure of offspring to environmental factors, and psychological and familial factors, did not differ between those with and without FM, it was concluded that the high-level familial occurrence of the condition might be attributable to genetic factors [18]. Buskila and Neumann [19] further studied female FM patients and their close family members, such as blood relatives (parents, siblings, and children), and non-related members (husbands). The prevalence of FM among the blood relatives of FM patients was 26%, whereas that among non-related members was only 19%. Furthermore, pain sensitivity was measured using mean tender point counts. The pain sensitivities of young male and female relatives were significantly higher than those of controls. These two studies thus suggested that certain genetic factors were associated with pain sensitivity and the high-level familial occurrence of FM. Arnold et al. [20] also evaluated the familial aggregation of FM and pain sensitivity among 533 relatives of 78 probands with FM. The presence of FM was associated both with significant aggregation and higher tender point counts among the relatives of FM probands compared with those of rheumatoid arthritis probands. Another study by Arnold et al. [21] showed that the sibling recurrence risk for FM was 27.2% (95% confidence interval [CI], 22.5 to 31.9), yielding a sibling recurrence risk ratio of 13.6 (95% CI, 10.0 to 18.5).

Moreover, FM patients exhibit familial aggregations of psychological features, such as depression and personality traits; such findings also support the idea that genetic factors contribute to the development of FM. Glazer et al. [22] assessed shared personality traits in FM patients and their first-degree relatives. Personality traits were evaluated (using the Tridimensional Personality Questionnaire [TPQ]) in 129 female FM patients, 27 female relatives with undiagnosed FM, and 30 female relatives without FM. FM patients and relatives with FM exhibited higher scores on the ‘harm avoidance’ subscale than did relatives without FM. Although it was not possible to fully differentiate between genetic and nongenetic factors, it was concluded that hereditary factors for personality traits contributed to the development of FM.

The fact that familial aggregation and shared psychological traits are evident among patients with FM does not exclude roles for other non-genetic factors in the pathogenesis of FM. However, the findings described above do suggest that genetic factors make important contributions to the etiology of FM.

News

Influence of weather on daily symptoms of pain and fatigue in female patients with fibromyalgia: Arthritis Care & Research, The Dutch investigators evaluated impact of weather condition on fibromyalgia course in 333 women in medium age. The study show up that more the change than the climate itself has an impact on perception of fibromyalgia symptoms like pain sensation and chronic fatigue.
Strusberg et al. had different observation. They investigated 151 people suffering from rheumatoid arthritis, osteoarthritis and fibromyalgia syndrome. They have noticed clear impact of low temperature on pain perception. The study was published in the Journal of Rheumatology. The pain sensations was also clearly linked to the humidity and atmospheric pressure.

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