Assessment of anxiety and learning in adult rats after inflammatory nociceptive stimulus started on the first day of life, followed or not by analgesia

Abstract

There is growing evidence that the exposure to untreated pain in the neonatal period could lead to changes to the brain plasticity, which in long-term would be related to an adverse neurodevelopmental outcome in premature newborns. Moreover, the treatment with opioid, considered the strongest analgesic drug used in the neonatal intensive care units is not free of deleterious effects on the central nervous system. Objective: To evaluate the effect of a nociceptive stimulus performed in the postnatal day 1 of life (PN1), followed or not by analgesia, over the anxiety behavior and learning in rats on PN 75. Methods: Wistar male and female rats will be assigned to the following groups: 1) treatment with Complete Freund'adjuvant (CFA) into the subcutaneous of the left paw on PN1, which will cause a persistent inflammatory nociceptive stimulus; 2) treatment with fentanyl, by the subcutaneous injections into the back of the animal from PN1 to PN8; 3) combined treatment with CFA and fentanyl; 4) control, non-handled animals and 5) treatment with saline, injections in the subcutaneous of the left paw and into the back from PN1 to PN8. On PN75 the behavior tests open field and elevated plus maze will be commenced, followed by the test on the water maze. For the females, it will be analyzed the estrous cycle on the day of each test. For the statistical analysis, ANOVA will be used to evaluate the main effects: group and gender. For the open field, the following variables will be studied: time in each zone and total distance, for the elevated plus maze: the proportion of time spent in the open arms and the proportion of entries into the open arms (entries into open arms/total entries into open or closed arms) and for water maze: time for the animal to reach the plattaform (latency) and the total distance traveled. (AU)