title: Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury.
abstract: Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation.
authors.affiliation: Department of Anesthesiology, The 2nd Hospital of Shanxi Medical University, Taiyuan, 030001, China.|Department of Anesthesiology, Xiangya Hospitalaffiliated to Central South University, Changsha 410008, China.
authors.forename: Zhicong
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Pain Management and Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital affiliated to Fudan University, No.221, West Yan'an Road, Shanghai, 200040, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Pain Management and Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital affiliated to Fudan University, No.221, West Yan'an Road, Shanghai, 200040, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Preventive Medicine, College of Medicine, Tongji University, Shanghai 200092, China.
authors.forename: Zisheng
authors.initials: Z
authors.lastname: Ai
authors.affiliation: Department of Pain Management and Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital affiliated to Fudan University, No.221, West Yan'an Road, Shanghai, 200040, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001343:Autophagy; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D037502:Galectin 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy*; D010368:Pectins / Q000494:pharmacology*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D037502:Galectin 3; D008070:Lipopolysaccharides; C586814:citrus pectin; D010368:Pectins