Early postnatal nociceptive stimulation results in deficits of spatial memory in male rats

Abstract

Prematurely-born infants are exposed to multiple invasive procedures while in the intensive care unit. Newborn rats and humans have similar behavioral responses to noxious stimulation. Previous studies have shown that early noxious stimuli may alter dentate gyrus neurogenesis and the behavioral repertoire of adult rats. We evaluated the late effects of noxious stimulation administered during different phases of development on two spatial memory tests; object recognition (OR) and Morris water maze (WM) tests. Noxious stimulation was induced by an intra-plantar injection of complete Freund's adjuvant (CFA) on postnatal (P) day 1 (group P1) or 8 (P8). Control animals were not stimulated. Behavioral tests were conducted on P60 in both male and female animals. In the WM, three domains were evaluated: acquisition, probe trial performance and reversal re-acquisition. The number of Nissl stained cells in the dentate granule cell layer was assessed by stereological counting. The OR test revealed that P1 male rats had poor long-term memory compared to the control and P8 groups. In the WM, no short- or long-term memory differences were detected between early postnatal-stimulated male and female rats and their respective controls. However, the ability to find the hidden platform in a new position was reduced in P1 male rats. The number of dentate granule cells in P8 males was higher than in all other groups. This study demonstrates that noxious stimulation on P1 results in spatial learning deficits in male animals, but does not disrupt the development of the hippocampus-dependent strategies of learning and memory.

Repeated neonatal needle‐prick stimulation increases inflammatory mechanical hypersensitivity in adult rats

“…There is abundant evidence from animal studies that repetitive pain and/or stress in early life can alter both the structure and function of the developing brain and, consequently, alter pain and/or stress responses in adulthood. Amaral et al (2015) have demonstrated that inflammatory nociceptive stimulation in the first postnatal week reduces the time spent exploring novel objects and affects long‐term memory in male animals. Mooney‐Leber et al (2018) showed that both neonatal isolation and repeated pain altered the corticosterone levels and the glutamate levels within the frontal cortex and hippocampus.…”

“…Many studies have demonstrated that the neurogenic effects of early repetitive noxious experiences are limited to PND 1 (postnatal day 1) and PND 8 (Malheiros et al, 2014; Amaral et al, 2015; den Hoogen et al, 2017) and that repetitive stimulation of the nociceptive system in a rat model using needle pricks in the hind‐paw closely mimics the clinical situation of infants in NICU (den Hoogen et al, 2017). In contrast, repeated procedural pain during the first 14–15 days of life in rat pups resulted in impairment of long‐term memory (Nuseir et al, 2017) and sensory and motor functions (Sanada et al, 2014; Carmo Ede et al, 2016).…”

The Long-Term Effects of Neonatal Inflammatory Pain on Cognitive Function and Stress Hormones Depend on the Heterogeneity of the Adolescent Period of Development in Male and Female Rats

“…Inflammatory pain caused by the intra-plantar injection of carrageenan (1%) on the day of birth, P0, resulted in spatial memory deficits also in adult rats (Henderson et al, 2015), and dysregulated the HPA axis (Victoria et al, 2013). Complete Freund's adjuvant on P1 did not affect short-or long-term memory in male or female rats on P60, but resulted in spatial learning deficits in males (Amaral et al, 2015). Therefore, although there are some inconsistencies, in general early experiences of painful injury can disrupt adult spatial learning/memory processes.…”

Adult brain activation in response to pain is changed by neonatal painful stimulation according to sex: A manganese‐enhanced MRI study

“…Complete Freund's adjuvant (CFA) is used as a model of persistent hind paw peripheral inflammation, that showed that, as adults, the animals had altered responses to sensory stimulation (Ruda, Ling, Hohmann, Peng, & Tachibana, 2000). So, by means of a subcutaneous injection of CFA in neonatal rat pups, we have been able to study the long‐term consequences of such early activation of the nociceptive system selectively, on behavior and neurogenesis (Amaral et al., 2015; Leslie et al., 2011; Lima et al., 2014; Malheiros, Lima, et al, 2014; Negrigo, Medeiros, Guinsburg, & Covolan, 2011) without concurrent tactile afferent information. In this study, we aimed to use this neonatal rat model investigate whether inflammatory painful stimulation in the first postnatal week on postnatal day 1 or 8 (P1 or P8) could promote long‐term effects on pain‐related pathways within the CNS, when the same noxious stimulus is applied in adulthood.…”