Genetics and epigenetic of pain Flashcards
Q: What contributes to the variability in pain experience across populations?
A: Genetics, shared environment, and non-shared environment contribute to pain variability.
Q: What does the bell curve of pain sensitivity indicate?
A: It shows the distribution of pain sensitivity, with most people in the “normal” range and fewer people being insensitive or hypersensitive.
Q: How do genes and environment interact to influence pain?
A: Genes (nature) provide a baseline for pain sensitivity, while environment (nurture) can modify that baseline through factors like stress or injury.
Q: Why do children from the same family differ in pain experience?
A: Genetic variability and non-shared environmental factors such as individual experiences.
Q: What is heritability (h²) in the context of pain?
A: The proportion of pain variability in a population that can be attributed to genetic differences.
Q: Which chronic pain conditions are highly heritable?
A: Conditions like lower back pain, neck pain, and fibromyalgia, with heritability ranging from 0.3 to 0.68.
Q: What is the significance of heritability in chronic pain research?
A: It highlights the role of genetics in pain sensitivity but also shows that environmental factors are important.
Q: What is linkage analysis in genetics?
A: A method that identifies chromosomal regions associated with disease by studying families, but it returns large regions of linkage.
Q: What is a GWAS and why is it important for pain research?
A: A genome-wide association study identifies SNPs across the genome associated with pain, helping to find new genetic targets for study.
Q: What is the difference between an SNP and SNV?
A: SNPs are variations in DNA that occur in at least 1% of the population, while SNVs are rarer variants.
Q: What role do sodium channel genes like SCN9A play in pain?
A: Mutations in SCN9A (Nav1.7) are linked to both extreme pain conditions (erythromelalgia) and insensitivity to pain.
Q: What is epigenetics?
A: The study of heritable changes in gene expression that do not involve changes to the DNA sequence itself, such as DNA methylation and histone modification.
Q: How do histone modifications influence pain?
A: Histone modifications can alter chromatin structure, making genes more or less accessible for transcription, thus influencing pain sensitivity.
Q: What is DNA methylation and how does it relate to pain?
A: DNA methylation is the addition of methyl groups to DNA, which can silence genes. Changes in methylation patterns can regulate pain pathways.
Q: What are enhancers, and how are they involved in epigenetic regulation of pain?
A: Enhancers are DNA regions that increase the expression of nearby genes. In chronic pain, newly accessible enhancers may alter gene regulation in pain pathways.
Q: Why is effect size important in interpreting genetic studies of pain?
A: While statistical significance shows that a result is unlikely due to chance, effect size tells us how biologically meaningful the difference is, such as in pain sensitivity between smokers vs. non-smokers.
Q: How can population stratification affect genetic studies in pain?
A: Differences in ancestry can lead to confounding in genetic studies, making it appear that certain genes are linked to pain when in fact, the population groups differ.
Q: Why is low statistical power a problem in pain genetics research?
A: Low power means a study is less likely to detect true effects, and many small underpowered studies may lead to false positives in identifying pain-related genes.
Q: How does chronic pain relate to epigenetic modifications?
A: Long-term pain may cause lasting changes in gene expression through mechanisms like DNA methylation and histone modification, which can sensitize the nervous system.
Q: What is the role of microglia in neuropathic pain and epigenetic changes?
A: Microglia, immune cells in the nervous system, may undergo epigenetic changes in chronic pain, leading to increased sensitivity and pain persistence.
Q: How do environmental factors like stress and obesity contribute to pain via epigenetics?
A: These factors can cause epigenetic modifications that change gene expression, potentially making individuals more susceptible to chronic pain.
Q: How do nature and nurture interact to shape pain sensitivity?
A: Genetics (nature) set the baseline for pain, but environmental factors (nurture) such as stress, injury, and lifestyle can alter pain through epigenetic mechanisms.
Q: Why are monogenic disorders like erythromelalgia important in pain research?
A: They provide clear examples of how single-gene mutations can drastically alter pain perception, offering insights into more complex, polygenic pain disorders.
Q: How might epigenetics explain differences in pain sensitivity between individuals with the same genetic background?
A: Epigenetic changes, which can be influenced by environmental factors, may lead to differential gene expression, resulting in variable pain responses even in genetically identical individuals (e.g., MZ twins).
