I am a
Home I AM A Search Login

Papers of the Week

Papers: 26 Oct 2019 - 1 Nov 2019


Animal Studies

2019 Nov/Dec




The Effects of Acute Neonatal Pain on Expression of Corticotropin Releasing Hormone and Juvenile Anxiety in a Rodent Model.


Zuke JT, Rice M, Rudlong J, Paquin T, Russo E, Burman MA
eNeuro. 2019 Nov/Dec; 6(6).
PMID: 31601633.


Premature infants in the Neonatal Intensive Care Unit (NICU) may be subjected to numerous painful procedures without analgesics. One necessary, though acutely painful, procedure is the use of heel lances to monitor blood composition. The current study examined the acute effects of neonatal pain on maternal behavior as well as amygdalar and hypothalamic activation, and the long-term effects of neonatal pain on later-life anxiety-like behavior, using a rodent model. Neonatal manipulations consisted of either painful needle pricks or non-painful tactile stimulation in subjects' left plantar paw surface which occurred four times daily during the first week of life (PND 1 – 7). Additionally, maternal behaviors in manipulated litters were compared against undisturbed litters via scoring of videotaped interactions to examine the long-term effects of pain on dam-pup interactions. Select subjects underwent neonatal brain collection (PND 6) and fluorescent hybridization (FISH) for corticotropin releasing hormone (CRH) and the immediate early gene c-fos. Other subjects were raised to juvenile age (PND 24 and PND 25) and underwent innate anxiety testing utilizing an elevated plus maze protocol. FISH indicated that neonatal pain influenced amygdalar CRH and c-fos expression, predominately in males. No significant increase in c-fos or CRH expression was observed in the hypothalamus. Additionally, neonatal pain altered anxiety behaviors independent of sex, with neonatal pain subjects showing the highest frequency of exploratory behavior. Neonatal manipulations did not alter maternal behaviors. Overall, neonatal pain drives CRH expression and produces behavioral changes in anxiety that persist until the juvenile stage. This report expands on current rodent model research performed to assess the long-term effects of highly utilized neonatal intensive care unit (NICU) procedures. The NICU plays an integral role in pediatric medicine by significantly reducing infant mortality and providing necessary procedures to preterm or unwell newborns. However, procedures in the NICU are often stressful and painful. A common procedure performed in the NICU is heel lances to monitor blood composition. This, along with numerous other painful procedures, are often performed on NICU babies without the benefit of analgesics. Our study identifies key neurological indicators which are altered in response to neonatal pain. Additionally, we explore the later anxiety of subjects exposed to neonatal pain.