title: Inhibition of the Rho/Rho kinase pathway prevents lipopolysaccharide-induced hyperalgesia and the release of TNF-α and IL-1β in the mouse spinal cord.
abstract: Administration of lipopolysaccharide (LPS) by various routes produces profound inflammatory pain hypersensitivity. However, the molecular events that induce this response remain largely uncharacterized. In the present study, we sought to elucidate the role of the Rho/Rho kinase (ROCK) pathway in the release of tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) following injection of LPS into the mouse paw, which is associated with nociceptive behavior. The spinal cord of LPS-treated mice showed increased active GTP-bound RhoA and upregulation of ROCK2 and c-fos compared to the normal saline group. Furthermore, the inflammation-related cytokines TNF-α and IL-1β were markedly increased in the spinal dorsal horn after intraplantar injection of LPS. However, the latter effects were prevented by prophylactic intrathecal administration of the Rho inhibitor (C3 exoenzyme) or the ROCK inhibitor (Y27632). Collectively, our results suggest that the Rho/ROCK signaling pathway plays a critical role in LPS-induced inflammatory pain and that this pathway is coincident with the release of the pro-nociceptive cytokines TNF-α and IL-1β, which produces hyperalgesia.
authors.affiliation: Clinical Medical College of Yangzhou University &Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, China.
authors.forename: Cunjin
authors.initials: C
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Anesthesiology &Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Song
authors.affiliation: Clinical Medical College of Yangzhou University &Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Clinical Medical College of Yangzhou University &Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Clinical Medical College of Yangzhou University &Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, China.
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Fang
authors.affiliation: Clinical Medical College of Yangzhou University &Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Clinical Medical College of Yangzhou University &Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Du
authors.affiliation: Clinical Medical College of Yangzhou University &Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006614:Hindlimb; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D007278:Injections, Spinal; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000502:physiology; D010147:Pain Measurement; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D015398:Signal Transduction; D066148:Spinal Cord Dorsal Horn; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D000577:Amides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C108830:Y 27632; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases; D001905:Botulinum Toxins; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein