Acta Anatomica Sinica ›› 2022, Vol. 53 ›› Issue (4): 412-417.doi: 10.16098/j.issn.0529-1356.2022.04.002

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Effect and mechanism of bromodomain-containing protein 4 inhibitor JQ1 on formaldehyde solution induced inflammatory pain in mice

CHEN  Ling1 LIU  Zhi-wen2  YANG  Bin2  ZHOU  Xin3  XIE  Zhi-yan ZENG  Jia-yu ZHAO  Ke-xin3  CAO  Wen-yu3* ZHONG  Xiao-lin1*   

  1. 1.Department of Endocrinology and Metabolism, the First Affiliated Hospital of University of South China, Hu’nan Hengyang 421001, China; 2.Institute of Clinical Anesthesiology, the Second Affiliated Hospital of University of South China, Hu’nan Hengyang 421001, China;  3.Clinical Anatomy and Reproductive Medicine Application Institute, Hengyang Medical School, University of South China, Hu’nan Hengyang 421001, China
  • Received:2020-10-22 Revised:2021-01-15 Online:2022-08-06 Published:2022-09-11
  • Contact: CAO Wen-yu;ZHONG Xiao-lin E-mail:zhxl20130623@163.com

Abstract:

Objective  To explore the expression and role of bromodomain-containing protein 4(BRD4) in spinal cord of mice which suffered inflammatory pain induced by formaldehyde solution.    Methods  Thirty-two ICR mice were randomly divided into normal saline group and formaldehyde injection 5 minutes, 30 minutes and 60 minutes groups, with 8 mice in each group. The expression of BRD4 protein and mRNA in spinal cord of mice in each group were detected by Western blotting (n=4/group) and Real-time PCR (n=4/group); 66 mice were randomly divided into formaldehyde injection group, vehicle (DMSO) plus formaldehyde injection group and 6.25, 12.5, 25 and 50 mg/kg JQ1 injection plus formaldehyde solution group, with 11 mice in each group. The effect of BRD4 inhibitor JQ1 on spontaneous pain in each group was observed (n=11/group); Immunohistochemistry (n=3/group), Real-time PCR (n=4/group) or Western blotting (n= 4/group) were used to detect the effects of 25 mg/kg JQ1 on the expression of c-fos and glutamate receptor 2(GluR2) in the spinal cord of model mice.    Results  The result  showed that levels of BRD4 protein (P<0.01) and mRNA in spinal cord increased significantly 30 min and 60 min after formaldehyde solution injection (P<0.05). The behavioral test showed that both 25 mg/kg and 50 mg/kg JQ1 administration could reduce the second phase spontaneous pain compared with the solvent (DMSO) group (P<0.05). Furthermore, immunohistochemistry and Real-time PCR result  showed that 25 mg/kg JQ1 injection could significantly reduce positive numbers (P<0.01) and high mRNA expression of c-fos in mouse spinal cord induced by formaldehyde solution (P<0.05), and the Western blotting result  showed that 25 mg/kg JQ1 administration could significantly reduce the expression of glutamate receptor GluR2 (P<0.001).     Conclusion  BRD4 may play an important role in the induction of central sensitization of inflammatory pain, and JQ1 may alleviate inflammatory pain behavior by inhibiting the formation of central sensitization of pain.

Key words: Bromodomain-containing protein 4, Inflammatory pain, Central sensitization, Spinal cord,  , Western blotting,  , Mouse

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