2. Academic Validation
  3. Spexin/NPQ Induces FBJ Osteosarcoma Oncogene (Fos) and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model

Spexin/NPQ Induces FBJ Osteosarcoma Oncogene (Fos) and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model

  • Am J Pathol. 2019 Apr;189(4):886-899. doi: 10.1016/j.ajpath.2018.12.009.
Shuang-Yu Lv 1,  Binbin Cui 1,  Yanjie Yang 2,  Hua Du 3,  Xiaomei Zhang 1,  Yuchen Zhou 1,  Wenling Ye 1,  Xiaobo Nie 1,  Yang Li 4,  Qun Wang 1,  Wei-Dong Chen 5,  Yan-Dong Wang 6
Affiliations

Affiliations

  • 1 Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, China.
  • 2 Laboratory of Cell Signal Transduction, School of Medicine, Henan University, Kaifeng, China.
  • 3 Department of Pathology, College of Basic Medicine, Inner Mongolia Medical University, Hohhot, China.
  • 4 Department of Orthopaedics, The 969th Hospital of People's Liberation Army of China, Hohhot, China.
  • 5 Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Henan University, Kaifeng, China; Department of Pathology, College of Basic Medicine, Inner Mongolia Medical University, Hohhot, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. Electronic address: [email protected].
PMID: 30664863 DOI: 10.1016/j.ajpath.2018.12.009
Abstract

Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in the periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. This study explored the mechanisms and effects of supraspinal spexin on inflammatory pain. The results from the mouse formalin test show that i.c.v. administration of spexin decreased licking/biting time during the late and early phases. The nonamidated spexin had no effect on pain response. The antinociception of spexin was blocked by Galanin receptor 3 antagonist SNAP 37889. The Galr3 and Adcy4 mRNA levels in the brain were increased after injection with spexin. The antinociceptive effects of spexin were completely reversed by Opioid Receptor antagonist naloxone and κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride. Spexin up-regulated the dynorphin and κ-opioid receptor gene and protein expression. PCR array assay and Real-Time PCR analysis show that spexin up-regulated the mRNA level of the FBJ osteosarcoma oncogene (Fos). T-5224, the inhibitor of c FBJ osteosarcoma oncogene (c-Fos)/activator protein 1 (AP-1), blocked the increased mRNA level of Pdyn and Oprk1 induced by spexin. I.C.V. spexin (2.43 mg/kg) increased the number of c-Fos-positive neurons in most subsections of periaqueductal gray. In addition, in the acetic acid-induced writhing test, i.c.v. spexin produced an antinociceptive effect. Our results indicate that spexin might be a novel neuropeptide with an antinociceptive effect against acute inflammatory pain.

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