Pain catastrophizing is associated with the Val66Met polymorphism of the brain-derived neurotrophic factor in fibromyalgia

Abstract

Background: Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome that impacts negatively patient's daily lives. Its pathogenesis is characterized by a complex relationship between biological and psychosocial factors not fully understood yet. Pain catastrophizing is associated with FM and is an important predictor of outcomes. This study aimed to answer two questions: (i) whether the allele and genotype frequencies of BDNF Val66Met (rs6265) polymorphism differs between FM patients and healthy controls (HC); and (ii) if the BDNF Val66Met polymorphism is a factor that predicts pain catastrophizing in FM. Methods: In a cross-sectional design, 108 FM patients and 108 HC were included. FM patients responded to the Brazilian Portuguese version of the Pain Catastrophizing Scale (BP-PCS) to assess pain catastrophizing, as well as other validated tools for anxiety (The State-Trait Anxiety Inventory-STAI), depression (Beck Depression Inventory II-BDI-II) and functional aspects (Fibromyalgia Impact Questionnaire-FIQ; Central Sensitization Inventory validated and adapted for Brazilian population-CSI-BP; Pittsburgh Sleep Quality Index-PSQI; and Resilience Scale). All subjects were genotyped for the BDNF Val66Met polymorphism. Results: Val allele was significantly more frequent in FM patients compared to the control group (p < 0.05). Also, FM patients with Val/Val genotype showed more pain catastrophizing thoughts, and this genotype was significantly associated with magnification and rumination dimensions of BP-PCS (p < 0.05). Furthermore, there were significant differences in levels of anxiety and symptoms of depression, years of education, and the functional situation between the FM and control groups. Conclusions: The findings show an association of BDNF Val66Met polymorphism with pain catastrophizing in FM, which opens new avenues to comprehend the interplay between molecular genetic characteristics and neuroplasticity mechanisms underpinning FM.

The genetic influence of the brain-derived neurotrophic factor Val66Met polymorphism in chronic low back pain

“…Several polymorphisms in the genes are contributing to serotonergic and adrenergic pathways that are associated with musculoskeletal pain [41]. Despite studies demonstrating evidence that the BDNF Val66Met polymorphism influences the cortical processing of experimental electrical pain stimuli in an indirect manner [4], or in pain catastrophizing [42], the findings in the present study did not show the influence of this polymorphism in chronic pain complaints.…”

A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia

“…Val-158-Val carriers exhibited significantly worse working memory measures than Met-158-Val carriers [ 29 ]. Val-158-Val carriers also showed more pain catastrophizing thought and higher levels of anxiety and symptoms of depression than Met-158-Val carriers [ 30 ]. Val-158-Val carriers reported higher sensory and affective ratings of pain along with negative internal affective states [ 31 ].…”

“…Similarly, the BDNF Val66Val SNP is associated with elevated plasma levels of high-sensitivity C-reactive protein and a higher body mass index [ 79 ]. Lastly, a BDNF polymorphism (rs6265) likely modulates pain signals at the level of the periaqueductal grey matter and is associated with pain catastrophizing in FM individuals [ 30 ].…”

Fatores genéticos associados à fibromialgia: uma revisão narrativa

“…Por isso, polimorfismos em genes relacionados a neurotransmissores e outros componentes que participam dessa via, agindo na modulação da dor como serotonina, norepinefrina, dopamina, entre outros, são frequentemente encontrados em estudos de associação genética com a FM (Lee et al, 2012;Ablin & Buskila, 2014;Zorina-Lichtenwalter et al, 2016). Porém, outros genes-alvo têm surgido, relacionados às vias responsáveis pelos mecanismos dos mais diversos sintomas que podem acometer esses pacientes, como inflamação, vascularização, estresse oxidativo, ciclo celular, entre outros (Karakus et al, 2012;Yigit et al, 2013;Inanir et al, 2015;da Silveira Alves et al, 2020;Estévez-López et al, 2021b).…”

“…Em mulheres brasileiras com FM, o alelo Val desse polimorfismo foi mais frequente em comparação ao grupo controle. Nesse mesmo grupo, o genótipo Val/Val foi associado a um aumento nos pensamentos catastrofistas de dor em comparação ao genótipo Val/Met, demonstrando uma associação do polimorfismo BDNF Val66Met com a catastrofização da dor na FM (da Silveira Alves et al, 2020). O genótipo Val/Val também foi associado a maiores níveis séricos de proteína C reativa de alta sensibilidade (marcador de processo inflamatório) e a um índice de massa corporal (IMC) médio mais alto em pacientes com FM em comparação aos pacientes com o genótipo heterozigoto Val/Met (Xiao et al, 2012).…”