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

CHEN Ling; LIU Zhi-Wen; YANG Bin; ZHOU Xin; XIE Zhi-Yan; ZENG Jia-Yu; ZHAO Ke-Xin; CAO Wen-Yu; ZHONG Xiao-Lin

doi:10.16098/j.issn.0529-1356.2022.04.002

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

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-yan³ ZENG Jia-yu³ ZHAO Ke-xin³ CAO Wen-yu^3* ZHONG Xiao-lin^1*

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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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CHEN Ling LIU Zhi-wen YANG Bin ZHOU Xin XIE Zhi-yan ZENG Jia-yu ZHAO Ke-xin CAO Wen-yu ZHONG Xiao-lin. Effect and mechanism of bromodomain-containing protein 4 inhibitor JQ1 on formaldehyde solution induced inflammatory pain in mice[J]. Acta Anatomica Sinica. 2022, 53(4): 412-417 https://doi.org/10.16098/j.issn.0529-1356.2022.04.002

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