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

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Abstract

Primary dysmenorrhea (PDM), menstrual pain without an organic cause, is a prevailing problem in women of reproductive age. We previously reported alterations of structure and functional connectivity (FC) in the periaqueductal gray (PAG) of PDM subjects. Given that the brain derived neurotrophic factor (BDNF) acts as a pain modulator within the PAG and the BDNF Val66Met polymorphism contributes towards susceptibility to PDM, the present study of imaging genetics set out to investigate the influence of, firstly, the BDNF Val66Met single nucleotide polymorphism and, secondly, the genotype-pain interplays on the descending pain modulatory systems in the context of PAG-seeded FC patterning. Fifty-six subjects with PDM and 60 controls participated in the current study of resting-state functional magnetic resonance imaging (fMRI) during the menstruation and peri-ovulatory phases; in parallel, blood samples were taken for genotyping. Our findings indicate that the BDNF Val66Met polymorphism is associated with the diverse functional expressions of the descending pain modulatory systems. Furthermore, PAG FC patterns in pain-free controls are altered in women with PDM in a genotype-specific manner. Such resilient brain dynamics may underpin the individual differences and shed light on the vulnerability for chronic pain disorders of PDM subjects.

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Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits.

Javeria A Hashmi, Marwan N Baliki, Lejian Huang … (2013)

Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain.

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Correlations and anticorrelations in resting-state functional connectivity MRI: a quantitative comparison of preprocessing strategies.

Andreas Weissenbacher, Christian Kasess, Florian Gerstl … (2009)

Resting-state data sets contain coherent fluctuations unrelated to neural processes originating from residual motion artefacts, respiration and cardiac action. Such confounding effects may introduce correlations and cause an overestimation of functional connectivity strengths. In this study we applied several multidimensional linear regression approaches to remove artificial coherencies and examined the impact of preprocessing on sensitivity and specificity of functional connectivity results in simulated data and resting-state data sets from 40 subjects. Furthermore, we aimed at clarifying possible causes of anticorrelations and test the hypothesis that anticorrelations are introduced via certain preprocessing approaches, with particular focus on the effects of regression against the global signal. Our results show that preprocessing in general greatly increased connection specificity, in particular correction for global signal fluctuations almost doubled connection specificity. However, widespread anticorrelated networks were only found when regression against the global signal was applied. Results in simulated data sets compared with result of human data strongly suggest that anticorrelations are indeed introduced by global signal regression and should therefore be interpreted very carefully. In addition, global signal regression may also reduce the sensitivity for detecting true correlations, i.e. increase the number of false negatives. Concluding from our results we suggest that is highly recommended to apply correction against realignment parameters, white matter and ventricular time courses, as well as the global signal to maximize the specificity of positive resting-state correlations.

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The prevalence and risk factors of dysmenorrhea.

Hong Ju, Mark Jones, Gita Mishra (2014)

Dysmenorrhea is a common menstrual complaint with a major impact on women's quality of life, work productivity, and health-care utilization. A comprehensive review was performed on longitudinal or case-control or cross-sectional studies with large community-based samples to accurately determine the prevalence and/or incidence and risk factors of dysmenorrhea. Fifteen primary studies, published between 2002 and 2011, met the inclusion criteria. The prevalence of dysmenorrhea varies between 16% and 91% in women of reproductive age, with severe pain in 2%-29% of the women studied. Women's age, parity, and use of oral contraceptives were inversely associated with dysmenorrhea, and high stress increased the risk of dysmenorrhea. The effect sizes were generally modest to moderate, with odds ratios varying between 1 and 4. Family history of dysmenorrhea strongly increased its risk, with odds ratios between 3.8 and 20.7. Inconclusive evidence was found for modifiable factors such as cigarette smoking, diet, obesity, depression, and abuse. Dysmenorrhea is a significant symptom for a large proportion of women of reproductive age; however, severe pain limiting daily activities is less common. This review confirms that dysmenorrhea improves with increased age, parity, and use of oral contraceptives and is positively associated with stress and family history of dysmenorrhea.

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Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 24 March 2016

Publication date Collection: 2016

Volume: 6

Electronic Location Identifier: 23639

Affiliations

[1 ]Institute of Brain Science, School of Medicine, National Yang-Ming University , Taipei, Taiwan

[2 ]Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University , Taipei, Taiwan

[3 ]Institute of Public Health, School of Medicine, National Yang-Ming University , Taipei, Taiwan

[4 ]Institute of Biomedical Informatics, School of Medicine, National Yang-Ming University , Taipei, Taiwan

[5 ]Integrated Brain Research Unit, Division of Clinical Research, Department of Medical Research, Taipei Veterans General Hospital , Taipei, Taiwan

[6 ]Department of Obstetrics and Gynecology, Taipei Veterans General Hospital , Taipei, Taiwan

[7 ]Laboratory of Microbiology, Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital , Taipei, Taiwan

Author notes

[a ] lfchen@ 123456ym.edu.tw

[b ] jchsieh@ 123456ym.edu.tw or jchsieh@ 123456vghtpe.gov.tw

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Publisher Item ID: srep23639

DOI: 10.1038/srep23639

PMC ID: 4806293

PubMed ID: 27010666

SO-VID: aa30d94e-8b54-480b-bd48-aa33b5d6da3a

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

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Most cited references 35

Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits.

Correlations and anticorrelations in resting-state functional connectivity MRI: a quantitative comparison of preprocessing strategies.

The prevalence and risk factors of dysmenorrhea.

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