Association of Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism with Primary Dysmenorrhea

Abstract

Primary dysmenorrhea (PDM), the most prevalent menstrual cycle-related problem in women of reproductive age, is associated with negative moods. Whether the menstrual pain and negative moods have a genetic basis remains unknown. Brain-derived neurotrophic factor (BDNF) plays a key role in the production of central sensitization and contributes to chronic pain conditions. BDNF has also been implicated in stress-related mood disorders. We screened and genotyped the BDNF Val66Met polymorphism (rs6265) in 99 Taiwanese (Asian) PDMs (20–30 years old) and 101 age-matched healthy female controls. We found that there was a significantly higher frequency of the Met allele of the BDNF Val66Met polymorphism in the PDM group. Furthermore, BDNF Met/Met homozygosity had a significantly stronger association with PDM compared with Val carrier status. Subsequent behavioral/hormonal assessments of sub-groups (PDMs = 78, controls = 81; eligible for longitudinal multimodal neuroimaging battery studies) revealed that the BDNF Met/Met homozygous PDMs exhibited a higher menstrual pain score (sensory dimension) and a more anxious mood than the Val carrier PDMs during the menstrual phase. Although preliminary, our study suggests that the BDNF Val66Met polymorphism is associated with PDM in Taiwanese (Asian) people, and BDNF Met/Met homozygosity may be associated with an increased risk of PDM. Our data also suggest the BDNF Val66Met polymorphism as a possible regulator of menstrual pain and pain-related emotions in PDM. Absence of thermal hypersensitivity may connote an ethnic attribution. The presentation of our findings calls for further genetic and neuroscientific investigations of PDM.

Associated Factors and Outcomes of Dysmenorrhea Among Female Nursing Students at King Abdulaziz University

“…Reduced progesterone may cause the increased production of prostaglandin, which leads to increased uterine muscle contraction, resulting in dysmenorrhea ]. 19 [ Although a high percentage of low haemoglobin was identified among dysmenorrheal nursing students in the present study, a statistically significant association between the severity of dysmenorrhea and low haemoglobin levels was not found. This is consistent with a study by Karanth and Liya, which reported that anaemia did not have a significant association with dysmenorrhea [7].…”

The BDNF Val66Met polymorphism is associated with the functional connectivity dynamics of pain modulatory systems in primary dysmenorrhea

“…This effect may be mediated through the neurotrophin-induced neuroplasticity of various pain modulatory systems or via a direct BDNF neurotransmitter-like effect on the brainstem monoaminergic nuclei 14 , such as the raphe nuclei or the PAG. We have reported in our preliminary genetic association study that BDNF Val66Met polymorphism may contribute to the susceptibility of women to PDM 16 . In addition, presence of chronic pain (e.g., low back pain) may enhance genetic sensitivity to experimental pain when the Met allele is present 15 , indicating BDNF Val66Met polymorphism genotype-pain interplays and suggesting maladaptive neuroplasticity in Met allele carriers.…”

Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

“…Both human and mouse 66Met allele carriers have been shown to have smaller bilateral hippocampi, in addition to lower gray mater volumes (e.g., prefrontal cortex), and reduced white matter tract integrity when compared to 66Val homozygote controls [104,105,106,107,108,109,110]. Furthermore, adult human and rat studies have shown that 66Met carriers may be at higher risk for developing chronic pain, PTSD, anxiety and depressive disorders [111,112,113,114,115,116,117,118,119]. Therefore, stress-regulated BDNF may be another mechanism through which genes may increase susceptibility to chronic pain and comorbid mental health conditions.…”