Influence of Cerebral Glucose Metabolism by Chronic Pain-Mediated Cognitive Impairment in Adolescent Rats

Chronic pain during adolescence can lead to mental health disorders in adulthood, but the underlying mechanism is still unclear. Furthermore, the homeostasis of cerebral glucose metabolism and neurotransmitter metabolic kinetics are closely associated with cognitive development and pain progression. The present study investigated changes in cognitive function and glucose metabolism in adult rats, which had experienced chronic pain during their adolescence. Here, spared nerve injury (SNI) surgery was conducted in 4-week-old male rats. Mechanical nociceptive reflex thresholds were analyzed, and SNI chronic pain (SNI-CP) animals were screened. Based on animal behavioral tests (open field, three-chambered social, novel object recognition and the Y maze), the SNI-CP animals showed learning and memory impairment and anxiety-like behaviors, compared to SNI no chronic pain (SNI-NCP) animals. The cerebral glucose metabolism in the prefrontal cortex and hippocampus of adult SNI-CP animals was decreased with positron emission tomography/computed tomography. GABA₂ and Glu₄ levels in the metabolic kinetics study were significantly decreased in the hippocampus, frontal cortex, and temporal cortex, and the expression of GLUT3 and GLUT4 was also significantly downregulated in the prefrontal cortex and hippocampus of adult rats in the SNI-CP group. These findings suggest that the rats which suffered chronic pain during adolescence have lower cerebral glucose metabolism in the cortex and hippocampus, which could be related to cognitive function during the development of the central nervous system.