Neurotransmitter imbalance and amygdala synaptic plasticity in lumbar disc herniation-induced chronic pain and related emotional Disturbances:A multi-omics analysis

Abstract

Chronic pain due to lumbar disc herniation (LDH) significantly impairs quality of life and is often accompanied by emotional disturbances, such as anxiety and depression. Despite the recognition of these comorbidities, the underlying neural mechanisms remain unclear. This study investigates the role of neurotransmitter imbalances and key regulatory molecules in LDH-induced chronic pain and related emotional disturbances, with a focus on synaptic plasticity in the amygdala. A rat model of LDH was developed using male Sprague-Dawley rats. Behavioral assessments were conducted to evaluate pain hypersensitivity, anxiety, and depression-like behaviors. Cerebrospinal fluid (CSF) metabolomics and amygdala transcriptomics were employed to analyze neurotransmitter profiles and gene expression. In vitro experiments were conducted to explore the role of PRKCG in synaptic plasticity. Behavioral tests showed significant pain hypersensitivity and anxiety- and depression-like behavior in LDH rats. Metabolomic analysis revealed altered levels of glutamate and γ-aminobutyric acid (GABA) in the CSF, indicating neurotransmitter imbalances. Transcriptomic profiling identified changes in genes related to synaptic plasticity, including PRKCG. PRKCG knockdown led to reduced CAMKII phosphorylation and GRIA1 expression, supporting its role in modulating synaptic plasticity. This study provides evidence that neurotransmitter imbalances and alterations in synaptic plasticity within the amygdala may contribute to the persistence of chronic pain and associated emotional disturbances in LDH. PRKCG may represent a novel therapeutic target for treating both chronic pain and related emotional disturbances.