Related Experiment Video
Updated: Jun 4, 2025
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Exposure to perinatal trauma modifies nociception and gene expression in the prefrontal cortex and hypothalamus of
Marissa Sgro1, Zoe Kodila1, Sabrina Salberg1
1Department of Neuroscience, School of Translational Medicine, Monash University,Melbourne, Victoria, Australia.
Insights
Perinatal trauma, including intimate partner violence (IPV) and neglect, negatively impacts offspring neurodevelopment and pain processing. This study reveals epigenetic changes in mothers and offspring, offering targets for preventing chronic pain risk.
Area of Science:
- Neuroscience
- Developmental Biology
- Epigenetics
Background:
- The perinatal period is crucial for neurodevelopment, making the brain sensitive to early life stress.
- Trauma during this period, like intimate partner violence (IPV) and neglect, is linked to adverse health outcomes, including chronic pain.
- Mechanisms underlying the link between perinatal trauma and chronic pain are not fully understood, though epigenetics is implicated.
Purpose of the Study:
- To investigate the relationship between perinatal trauma (in utero IPV and early life neglect) and socio-emotional functioning, nociceptive sensitivity, and transcriptomic changes.
- To examine these effects in both dams (mothers) and their adolescent offspring.
- To explore potential epigenetic mechanisms contributing to the intergenerational risk of chronic pain.
Main Methods:
- Rat dams were exposed to intimate partner violence (IPV) or sham procedures during pregnancy.
- Offspring were subjected to early life neglect or control conditions post-birth.
- Adolescent offspring underwent plantar incision or sham injury, followed by assessment of nociception, socio-emotional behavior, and transcriptomic analysis in the prefrontal cortex (PFC) and hypothalamus.
Main Results:
- Perinatal trauma, combined with surgical procedures, altered nociception and emotional functioning in a sex-dependent manner in offspring.
- Transcriptomic analysis revealed changes in DNA transcription and expression in dams' PFC and hypothalamus.
- Offspring transcriptomes showed impaired immune regulation, stress-reactivity, microglia activation, and altered expression of chronic pain-associated genes.
Conclusions:
- Perinatal trauma significantly modifies offspring behavior, including nociceptive sensitivity and socio-emotional processing.
- The study provides insights into the epigenetic mechanisms underlying the intergenerational transmission of chronic pain risk.
- Findings highlight potential therapeutic targets for reversing trauma-induced epigenetic changes and preventing chronic pain.
Abstract:
The perinatal period encompasses a critical window for neurodevelopment that renders the brain highly responsive to experience. Trauma, such as intimate partner violence (IPV) and early life stress/neglect, during this period negatively affects physical and mental health outcomes, including increasing ones risk for chronic pain. Although epigenetic programming likely contributes, the mechanisms that drive the relationship between perinatal trauma and adverse health outcomes, are not fully understood. Therefore, we explored the relationship between perinatal trauma (in utero exposure to IPV and/or early life neglect) and socio-emotional functioning, nociceptive sensitivity, and transcriptomic changes within the prefrontal cortex (PFC) and hypothalamus in dams and their adolescent offspring. Rat dams were randomly assigned to an IPV (i.e., combined mild traumatic brain injury and strangulation) or sham procedure during pregnancy. Following birth, offspring were subsequently assigned the early life neglect or control paradigm. In adolescence, offspring received a plantar incision or sham injury. Perinatal trauma altered nociception and emotional functioning in a sex-dependent manner when combined with the surgical procedure. We identified transcriptomic changes related to DNA transcription and expression within the PFC and hypothalamus of the dams. Examination of the offspring transcriptome highlighted impairment in immune regulation, dysfunction in stress-reactivity, as well as microglia activation. We also identified altered expression of genes associated with chronic pain. This demonstrates that perinatal trauma modifies offspring behaviour, including nociceptive sensitivity. We provide insight into the mechanisms that contribute to the chronification of pain, thereby informing future research targeted at the generation of prevention and therapeutic strategies. PERSPECTIVE: Perinatal trauma impaired cognitive, socio-emotional, and pain processing in offspring, while also inducing changes in gene expression, in both mothers and offspring. The findings highlight possible mechanisms responsible for intergenerational transmission of risk for chronic pain and provide targets for therapeutics which could potentially reverse perinatal-trauma induced epigenetic change.
