p300 exerts an epigenetic role in chronic neuropathic pain through its acetyltransferase activity in rats following chronic constriction injury (CCI)

Molecular Pain

Qu-Lian Guo¹  Wang-yuan Zou¹  Zong-bing Song¹  Rui-min Chang²  Qian Li¹  Chang-Sheng Huang¹  Xiao-Yan Zhu¹ 

[1] Department of Anesthesiology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha City, Hunan, 410008, China;Liver Cancer Laboratory, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha City, Hunan, 410008, China

关键词: CCI;    Acetyltransferase activity;    COX-2;    p300;    Neuropathic pain;   

Others  :  863321
DOI  :  10.1186/1744-8069-8-84

 received in 2012-07-17, accepted in 2012-11-21,  发布年份 2012

【 摘 要 】

Background

Neuropathic pain is detrimental to human health; however, its pathogenesis still remains largely unknown. Overexpression of pain-associated genes and increased nociceptive somato-sensitivity are well observed in neuropathic pain. The importance of epigenetic mechanisms in regulating the expression of pro- or anti-nociceptive genes has been revealed by studies recently, and we hypothesize that the transcriptional coactivator and the histone acetyltransferase E1A binding protein p300 (p300), as a part of the epigenetic mechanisms of gene regulation, may be involved in the pathogenesis of neuropathic pain induced by chronic constriction injury (CCI). To test this hypothesis, two different approaches were used in this study: (I) down-regulating p300 with specific small hairpin RNA (shRNA) and (II) chemical inhibition of p300 acetyltransferase activity by a small molecule inhibitor, C646.

Results

Using the CCI rat model, we found that the p300 expression was increased in the lumbar spinal cord on day 14 after CCI. The treatment with intrathecal p300 shRNA reversed CCI-induced mechanical allodynia and thermal hyperalgesia, and suppressed the expression of cyclooxygenase-2 (COX-2), a neuropathic pain-associated factor. Furthermore, C646, an inhibitor of p300 acetyltransferase, also attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord.

Conclusions

The results suggest that, through its acetyltransferase activity in the spinal cord after CCI, p300 epigenetically plays an important role in neuropathic pain. Inhibiting p300, using interfering RNA or C646, may be a promising approach to the development of new neuropathic pain therapies.

【 授权许可】

   
2012 Zhu et al.; licensee BioMed Central Ltd.

【 图 表 】

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