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Updated: Jul 1, 2025

Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
Chronic Pain-Related Cognitive Deficits: Preclinical Insights into Molecular, Cellular, and Circuit Mechanisms
Siyi Han1, Jie Wang2, Wen Zhang3
1Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, Hubei, China.
Abstract:
Cognitive impairment is a common comorbidity of chronic pain, significantly disrupting patients' quality of life. Despite this comorbidity being clinically recognized, the underlying neuropathological mechanisms remain unclear. Recent preclinical studies have focused on the fundamental mechanisms underlying the coexistence of chronic pain and cognitive decline. Pain chronification is accompanied by structural and functional changes in the neural substrate of cognition. Based on the developments in electrophysiology and optogenetics/chemogenetics, we summarized the relevant neural circuits involved in pain-induced cognitive impairment, as well as changes in connectivity and function in brain regions. We then present the cellular and molecular alternations related to pain-induced cognitive impairment in preclinical studies, mainly including modifications in neuronal excitability and structure, synaptic plasticity, glial cells and cytokines, neurotransmitters and other neurochemicals, and the gut-brain axis. Finally, we also discussed the potential treatment strategies and future research directions.
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