Related Experiment Video
Updated: Mar 10, 2026
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Neonatal repetitive pain in rats leads to impaired spatial learning and dysregulated hypothalamic-pituitary-adrenal
Mengying Chen1, Dongqing Xia1, Cuiting Min1
1Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China.
Insights
Neonatal repetitive pain in rats, from repeated needle procedures, led to long-term mechanical hypersensitivity and altered cognitive and emotional behaviors. Stress responses also changed across development, indicating lasting effects of early pain exposure.
Area of Science:
- Neuroscience
- Developmental Biology
- Pain Research
Background:
- Preterm birth necessitates hospitalization for infants, often involving repetitive painful procedures.
- The long-term impact of neonatal pain on behavior and neuroendocrine function remains largely unknown.
Purpose of the Study:
- To investigate the long-term effects of neonatal repetitive pain on cognitive and emotional behaviors.
- To examine the influence of neonatal pain on hypothalamic-pituitary-adrenal (HPA) axis function in rats from prepuberty to adulthood.
Main Methods:
- Rats were exposed to repetitive needle-stick procedures (Needle group) or tactile stimulation (Tactile group) from postnatal day 8 to 85.
- Behavioral tests included mechanical hypersensitivity assessment, Morris water maze (spatial learning/memory), and Open-field test (anxiety/locomotion).
- HPA axis function was assessed by measuring stress responsiveness at different developmental stages.
Main Results:
- The Needle group exhibited persistent mechanical hypersensitivity.
- Spatial learning and memory were impaired in the Needle group, evidenced by longer platform acquisition times and fewer platform crossings.
- The Needle group showed altered anxiety-like behaviors and changes in HPA axis stress responsiveness, with decreased responsiveness in younger animals and increased responsiveness in adults.
Conclusions:
- Neonatal repetitive pain during a critical developmental period can lead to enduring behavioral and neuroendocrine disturbances.
- These effects manifest as long-term hypersensitivity, cognitive deficits, and altered stress responses extending into adulthood.
- Findings highlight the significant consequences of early life pain exposure on neurodevelopment.
Abstract:
Preterm birth is a major health issue. As part of their life-saving care, most preterm infants require hospitalization and are inevitably exposed to repetitive skin-breaking procedures. The long-term effects of neonatal repetitive pain on cognitive and emotional behaviors involving hypothalamic-pituitary-adrenal (HPA) axis function in young and adult rats are unknown. From P8 to P85, mechanical hypersensitivity of the bilateral hindpaws was observed in the Needle group (P < 0.001). Compared with the Tactile group, the Needle group took longer to find the platform on P30 than on P29 (P = 0.03), with a decreased number of original platform site crossings during the probe trial of the Morris water maze test (P = 0.026). Moreover, the Needle group spent more time and took longer distances in the central area than the Tactile group in the Open-field test, both in prepubertal and adult rats (P < 0.05). The HPA axis function in the Needle group differed from the Tactile group (P < 0.05), with decreased stress responsiveness in prepuberty and puberty (P < 0.05) and increased stress responsiveness in adulthood (P < 0.05). This study indicates that repetitive pain that occurs during a critical period may cause severe consequences, with behavioral and neuroendocrine disturbances developing through prepuberty to adult life.
