Research Article: Lasting Developmental Effects of Neonatal Fentanyl Exposure in Preweanling Rats

Date Published: October 19, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Dora Catré, Maria Francelina Lopes, António Silvério Cabrita.


The present study aimed to determine whether neonatal treatment with fentanyl has lasting effects on stressed developing brain. Six-day-old rats were assigned to one of three groups (10 males/group): (1) fentanyl (incision+fentanyl), (2) saline (incision+0.9% saline), and (3) unoperated (unoperated sham). Pups with a plantar paw incision received repetitive subcutaneous injections of fentanyl or vehicle through postnatal days (PNDs) 6 to 8. A nonoperated sham group served as nonstressed control. Studies included assessment of development from PND 6 to PND 21 (growth indices and behavioral testing). Fentanyl administered twice daily for three days after surgical incision had no impact on early growth and development, as measured on PND 9, but showed a lasting impact on later growth, enhanced behavioral development, and lower anxiety, as measured through PNDs 10–21. While this does not completely support a benefit from such treatment, our findings may contribute to support the neonatal use of fentanyl, when indicated, even in premature newborns.

Partial Text

Fentanyl, a potent μ-opioid agonist, is a synthetic drug that has been widely used for pain management [1, 2] and as a general anesthetic for surgical procedures in pediatrics [3–5], namely in surgical neonatal intensive care units. In a previous study, fentanyl was identified as being within the 5 medications with the highest exposure rates in a pediatric intensive care unit [2].

The present study was designed to assess whether exposure to repetitive injections of fentanyl during brain development influences later physical and neurological outcomes. Using a neonatal postoperative pain model, this study demonstrates, for the first time, lasting effects on growth and behavior of rat pups that underwent repeated fentanyl exposure during early postnatal life, when tested as later pre-weanling rats. The results showed that repeated fentanyl exposure of an immature stressed animal significantly interferes with growth, cognitive function, behavioral reactivity to stress, neuromuscular and locomotor development, and balance and coordination. All these outcomes (Table 2) suggest a neurological impact with possible consequences, either positive or negative, later in life.