Introduction: Maternal exposure to nicotine, commonly through smoking or vaping, has been linked to a variety of long-lasting health effects in offspring. One of the most significant outcomes is the alteration of the hypothalamic-pituitary-adrenal (HPA) axis, which plays a key role in the body’s response to stress. Recent studies suggest that nicotine exposure during pregnancy can cause epigenetic modifications that affect stress responses in the next generation. These modifications may influence gene expression related to the HPA axis and pain regulation, contributing to increased vulnerability to stress-related disorders and chronic pain. This review aims to examine the relationship between maternal nicotine exposure, epigenetic changes, stress response, and pain, focusing on the intergenerational transmission of these effects.
Methods: To gather relevant information for this review, we conducted a systematic search using several scientific databases, including PubMed, Scopus, and Web of Science. Studies published between 2015 and 2023 were included. The keywords used in the search included "nicotine," "maternal exposure," "HPA axis," "epigenetic regulation," "stress response," "chronic pain," and "intergenerational effects." We focused on both animal and human studies that explored the impact of maternal nicotine exposure on the stress system, particularly epigenetic modifications in genes regulating the HPA axis and pain pathways. Only studies that examined the effects on the next generation were considered, with an emphasis on epigenetic mechanisms such as DNA methylation and histone modifications.
Results: The review reveals that maternal nicotine exposure leads to significant epigenetic changes in the offspring, particularly in genes involved in the regulation of the HPA axis. These changes can alter the body’s ability to manage stress effectively, making the offspring more susceptible to anxiety, depression, and other stress-related disorders. Studies show that nicotine exposure during pregnancy results in altered DNA methylation patterns and histone modifications in brain regions such as the hippocampus and prefrontal cortex, which are critical for stress response regulation. Moreover, nicotine’s effects extend beyond stress regulation and are linked to pain sensitivity. Changes in the expression of pain-related genes, such as opioid receptors and pain modulators, have been observed in offspring exposed to nicotine in utero. These epigenetic alterations in pain pathways may lead to heightened pain sensitivity and a predisposition to chronic pain conditions in the next generation. In addition, exposure to nicotine can alter the expression of genes that regulate inflammatory responses, further contributing to pain perception and stress responses. The interaction between nicotine, stress, and pain is complex. Nicotine-induced epigenetic modifications in the offspring not only affect the HPA axis but also influence neurotransmitter systems involved in pain processing, such as the opioid and endocannabinoid systems. These interactions highlight the role of epigenetics in shaping how the offspring respond to stress and pain throughout life.
Conclusion: Maternal nicotine exposure has profound epigenetic effects that influence both stress and pain regulation in the offspring. By altering the expression of genes involved in the HPA axis and pain pathways, nicotine exposure during pregnancy increases the risk of stress-related disorders and chronic pain in the next generation. Understanding the underlying epigenetic mechanisms provides new insights into the long-term effects of prenatal nicotine exposure and highlights potential therapeutic targets for managing these intergenerational effects. Future research should focus on identifying specific epigenetic modifications that could be targeted to mitigate the adverse health outcomes associated with maternal smoking and nicotine use.
Keywords: Nicotine, HPA Axis, Chronic Pain, DNA Methylation, Intergenerational Effects.