The Effects of Early Life Pain and Juvenile Fear Conditioning on CRF-Receptor Expression in the Amygdala and Hypothalamus

Early life pain and stress have lasting consequences on nervous system development that can interact with later stress or trauma to create a susceptibility to fear, anxiety, depression and chronic pain among other psychological disorders. Recent work has identified changes in corticotropin releasing factor signaling in limbic system structures, such as the amygdala and hypothalamus, as a key mechanism behind these changes – albeit in a sex-dependent manner. CRF has two major receptors, CRHR1 and CRHR2 which have also been shown to play key roles in fear and pain expression. The current work examines the effects of early life pain designed to mimic the neonatal medical trauma that occurs in the Neonatal Intensive Care Unit (NICU), paired with a juvenile trauma in the form of fear conditioning, on expression of crhr1 and crhr2 mRNA in the central (CeA) and basolateral (BLA) amygdala as well as the paraventricular (PVN) and ventromedial (VMH) hypothalamus. While prior work has demonstrated that early life pain significantly impacts expression of the CRF ligand, the current data demonstrate that early life pain and fear conditioning largely fail to affect CRH receptor expression in the amygdala. Modest changes in expression to crhr2 in a sex and region-specific manner were observed in the hypothalamus.