Exposure to Perinatal Trauma Modifies Nociception and Gene Expression in the Prefrontal Cortex and Hypothalamus of Adolescent Rats.

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.