Relationship Between Central Sensitization and Genetic Polymorphisms—A Case–Control Study in Fibromyalgia

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BACKGROUND: Fibromyalgia is a syndrome characterised by widespread chronic pain, which is believed to be mediated by a state of central sensitisation (CS). Based on the hypothesis that CS itself could have genetic determinants, our aim was to further explore this pathway. METHODS: This study included 201 women with fibromyalgia and 40 healthy women matched on age and menopausal status. The nociceptive flexion reflex (NFR) threshold was used as a surrogate marker of CS. Genotyping of 60 candidate-genes likely to influence the pathogenesis of fibromyalgia or chronic pain was explored in all subjects. RESULTS: The NFR threshold was lower in patients (n = 141, median and [interquartile range]: 34 mA [24-46]) than in controls (n = 35, 58 mA [44-77], p = 0.0003), but none of the tested polymorphism genotype was significant. An association was found between fibromyalgia and three polymorphisms related to TNF, TACR1, and IL10 genes, either by testing the simple allelic frequency or an additive model. When the analysis was adjusted on NFR threshold, only the association with TACR1 was still significant, along with other associations with polymorphisms related to FAAH, HTR1A, and MYT1L. Associations were however non significant when a Bonferroni's correction was applied. CONCLUSIONS: This study confirmed that CS is a major feature of fibromyalgia. Although several polymorphisms stand out in the analysis, no significant relationship between CS and 60 selected candidate-genes genotype could be highlighted. This information may help however to guide further research to explore this important pathway in larger well phenotyped cohorts. SIGNIFICANCE STATEMENT: Sixty selected fibromyalgia and pain candidate-genes have no significant association with the nociceptive flexion reflex, a surrogate marker of central sensitization in 201 fibromyalgia women. But the study may help however to guide further research to explore this important pathway in larger well phenotyped cohorts. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04624581.

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