In the present study, we investigated the effect of repeated neonatal morphine exposure and/or maternal deprivation(MD) on the nociceptive response and central biomarkers’ BDNF, IL-1β, and IL-4 levels at postnatal days 16(PND16), 30(PND30), and 60(PND60). At birth, the litters were standardized to contain 8 pups/dam (n = 58). From PND1 to PND10, the pups of the deprived groups were separated daily from their mothers for 3 h and divided into 5 groups: control(C), saline(S), morphine(M), deprived-saline(DS), and deprived-morphine (DM). The pups received subcutaneous injections of saline/morphine (5 μg) in the mid-scapular area between PND8 and PND14. Nociceptive responses were assessed by hot plate(HP) and tail-flick(TFL) tests and biomarker levels by ELISA. Thermal hyperalgesia(HP) was found in all assessments for the M, DS, and DM groups, and a decrease in nociceptive threshold(TFL) was found in the DS group at PND16; M and DM groups at PND30; and M, DS, and DM groups at PND60. There were interactions between treatment/deprivation/timepoint in all central biomarkers’ levels. The current study indicates that neonatal exposure to morphine and MD, which occurs in the pediatric ICU, can alter the nociceptive and neuroinflammatory responses
