title: Ligustilide Ameliorates Inflammatory Pain and Inhibits TLR4 Upregulation in Spinal Astrocytes Following Complete Freund's Adjuvant Peripheral Injection.
abstract: Ligustilide is a major component of Radix Angelica Sinensis and reported to have anti-inflammatory and anti-nociceptive effects. Toll-like receptor 4 (TLR4) has been shown to be expressed in the spinal cord and be involved in inflammatory pain and neuropathic pain. Whether ligustilide can inhibit spinal TLR4 expression in inflammatory pain is still unknown. In the present study, we intravenously injected ligustilide daily for 4 days, with the first injection given at 1 h before complete Freund's adjuvant (CFA) injection. We tested the analgesic effect of ligustilide by behavioral test and checked the expression and distribution of TLR4 in the spinal cord by real-time quantitative PCR, Western blot, and immunofluorescence. Our data showed that repeated daily intravenous treatment with ligustilide alleviated CFA-induced heat hyperalgesia and mechanical allodynia. The same treatment also inhibited CFA-induced TLR4 mRNA and protein increase in the spinal cord. Immunofluorescence double staining showed that TLR4 was predominantly expressed in spinal astrocytes. In primary cultured astrocytes, ligustilide dose-dependently reduced lipopolysaccharide-induced upregulation of TLR4 mRNA expression. These data indicate that ligustilide treatment reduces TLR4 expression in spinal astrocytes and is an effective therapy for inflammatory pain.
authors.affiliation: Department of Anesthesiology, The First People's Hospital of Yancheng, Yancheng, 224005, Jiangsu, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qian
authors.affiliation: Department of Anesthesiology, The First People's Hospital of Yancheng, Yancheng, 224005, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Lin-Xia
authors.initials: LX
authors.lastname: Zhao
authors.affiliation: Department of Anatomy, Medical School of Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Dong
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Yong-Jing
authors.initials: YJ
authors.lastname: Gao
authors.affiliation: Department of Anatomy, Medical School of Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, China. zhangzhijun6042@163.com.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006358:Hot Temperature; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; C027820:ligustilide; D005620:Freund's Adjuvant; D015107:4-Butyrolactone
keywords: Astrocytes; Complete Freund’s adjuvant; Inflammatory pain; Ligustilide; Toll-like receptor 4