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Background Fibromyalgia (FM) is a complex, centralized pain condition that is often difficult to diagnose and treat. FM is considered to have a genetic background due to its familial aggregation and due to findings from multiple candidate-gene studies implicating catecholaminergic and serotonergic neurotransmitter systems in chronic pain. However, a multi-factorial analysis of both genetic and environmental risk factors is lacking. A better characterization of the interplay of risk factors may assist in understanding the pathophysiology of FM, its clinical course, and assist in early diagnosis and treatment of the disorder. Methods This retrospective study included 60,367 total participants from 237 clinics across the USA. Of those, 2713 had been diagnosed with fibromyalgia, as indicated by ICD code. Logistic regression was used to test for associations of diagnosed FM in study subjects with COMT SNPs and COMT haplotypes, which were previously found to be linked with pain sensitivity, as well as demographics such as age, sex, and ethnicity. The minor allele frequencies of COMT SNPs in the FM population were compared with 1000 Genomes data using a χ2 test to determine significant deviations from the estimated population allelic frequencies. Results FM diagnosis was strongly associated with sex, age, and ethnicity. Females, those between 49 and 63 years, and non-Caucasians were at higher risk of FM. Females had 1.72 increased odds of FM ( p = 1.17 × 10 − 30 ). African-Americans were 1.52 times more likely to have a diagnosis of FM compared to Caucasians ( p = 3.11 × 10 − 12 ). Hispanics were less likely to have a diagnosis of FM compared to Caucasians ( p = 3.95 × 10 − 7 ). After adjusting for sex and ethnicity, those in the low age group and mid age group had 1.29 (p = 1.02 × 10 − 5 ) and 1.60 ( p = 1.93 × 10 − 18 ) increased odds of FM, respectively, compared to the high age group, where age was categorized by tertile (low (< 49), mid (49–63), and high (> 63)). The COMT haplotypes associated with pain sensitivity were not associated with FM, but African-Americans were 11.3 times more likely to have a high pain sensitivity COMT diplotype, regardless of FM diagnosis. However, the minor alleles of COMT SNPs rs4680 , rs4818 , rs4633 and rs6269 were overrepresented in the FM population overall, and varied when compared with ethnically-similar populations from 1000 Genomes. Conclusions ...

Summary Fibromyalgia (FM) is characterized by widespread muscle pain and soft tissue tenderness. However, a lack of definitive muscle pathology has made FM both a diagnostic and a treatment puzzle. Much of the evidence for pathology in FM lies in the central nervous system – in particular abnormal amplification of pain signals in the spinal cord – a manifestation of central sensitization. An emerging body of evidence posits that peripheral pain generated from the muscles and fascia may trigger and maintain central sensitization in FM. Since FM patients so frequently seek manual therapy to relieve muscle symptoms, the present study compared two different manual therapy techniques in a parallel study of women with FM. Eight subjects received myofascial release (MFR) while four subjects received Swedish massage, 90 min weekly for four weeks. Overall symptom burden and physical function were assessed by the Fibromyalgia Impact Questionnaire Revised (FIQ-R). A unique challenge for the manual therapist in treating conditions involving central sensitization is to determine if localized pain reduction can be achieved with targeted therapy in the context of ongoing widespread pain. Localized pain improvement was measured by a novel questionnaire developed for this study, the modified Nordic Musculoskeletal Questionnaire (NMQ). Between-group differences in FIQ-R did not reach statistical significance, but the total change scores on FIQ-R for the MFR group (mean = 10.14, SD = 16.2) trended in the hypothesized and positive direction compared to the Swedish massage group (mean = 0.33, SD = 4.93) yielding a positive Aikin separation test. Although overall modified NMQ scores improved in both groups there were no consistent focal areas of improvement for the Swedish massage group. In contrast, the MFR group reported consistent pain reductions in the neck and upper back regions on the NMQ. These data support the need for larger randomized controlled trials of MFR versus other massage techniques and support the assessment of localized pain reduction in future manual therapy studies in FM.