Fibromyalgia central sensitization lacks significant genetic association with 60 candidate genes

Fibromyalgia is a chronic pain syndrome characterized by widespread pain, often linked to central sensitization (CS), a state of heightened pain processing in the central nervous system. Despite its prevalence, the underlying mechanisms of CS in fibromyalgia are not fully understood, particularly regarding potential genetic predispositions. Current treatments often address symptoms without targeting the root cause, and identifying genetic determinants could pave the way for more personalized and effective therapies. This study aimed to explore if CS itself has genetic underpinnings by examining candidate gene polymorphisms.

Researchers conducted a case-control study involving 201 women diagnosed with fibromyalgia and 40 age- and menopausal status-matched healthy women. The nociceptive flexion reflex (NFR) threshold was measured as a surrogate marker for central sensitization. All participants underwent genotyping for 60 candidate genes, selected for their known or hypothesized roles in fibromyalgia pathogenesis or chronic pain. The primary endpoint was to identify significant associations between specific gene polymorphisms and the NFR threshold, as well as with the diagnosis of fibromyalgia itself.

The NFR threshold was significantly lower in fibromyalgia patients (n=141, median 34 mA [interquartile range 24-46]) compared to healthy controls (n=35, median 58 mA [44-77], p=0.0003), confirming central sensitization as a prominent feature. Initial analyses revealed associations between fibromyalgia and polymorphisms in the TNF, TACR1, and IL10 genes, both through simple allelic frequency and an additive model. When the analysis was adjusted for the NFR threshold, the association with TACR1 remained significant, alongside new associations with polymorphisms related to FAAH, HTR1A, and MYT1L genes. However, the most critical finding was that:

All observed associations, including those initially found, became non-significant after applying a Bonferroni's correction for multiple comparisons, indicating no robust genetic link between the 60 candidate genes and central sensitization or fibromyalgia in this cohort.