Galectin-related protein, a key contributor, drives diabetes-associated neuropathic pain
Abstract
Neuropathic pain associated with central sensitization is common in diabetic patients, but the underlying mechanisms remain unclear. Here, a proteomics screen identified a previously uncharacterized protein, galectin-related protein (LGALSL), which was significantly upregulated in cerebrospinal fluid and extracellular fluid of the anterior cingulate cortex (ACC) in diabetes-related neuropathic pain (DNP) model rats. Exogenous LGALSL administration reduced mechanical nociceptive thresholds by activating glutamatergic neurons in the ACC (ACC Glu ). Chemogenetic manipulations and functional assays revealed that neuron-derived LGALSL directly binds to vimentin on ACC astrocytes, activating those astrocytes. These activated astrocytes subsequently maintain ACC Glu hypersensitivity, driving mechanical hypersensitivity in diabetic rats. Blocking LGALSL–vimentin interactions with a synthetic peptide alleviated LGALSL-induced mechanical hypersensitivity. This study establishes LGALSL-dependent astrocyte-mediated hyperactivation of ACC Glu neurons as a new pathological mechanism of neuropathic pain in diabetes.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (12)
Danyang Chen
Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Jing Wang
Hunan Cancer Hospital Changsha China
Xiang-Jie Song
Core Facility Centre for Life Science, Division of Life Sciences and Medicine, University of Science and Technology of China
Zi-Jiao Ding
Department of Anatomy, Anhui Provincial Key Laboratory for Brain Bank Construction and Resource Utilization, School of Basic Medical Sciences, Anhui Medical University
Qianqian Lou
Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Yuan-Yuan Chen
Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Meng-Yuan Wang
Department of Endocrinology and Metabolism, The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China
Xin-Lu Yang
Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Zhi Zhang
Juan Li
Wei Wang
Haitao Wang
Department of Central Laboratory, College & Hospital of Stomatology, Anhui Provincial Key Laboratory of Oral Diseases Research, Anhui Medical University